Prognostic Value of Exercise Capacity in Kidney Transplant Candidates.

Background Exercise stress testing for cardiovascular assessment in kidney transplant candidates has been shown to be a feasible alternative to pharmacologic methods. Exercise stress testing allows the additional assessment of exercise capacity, which may have prognostic value for long-term cardiovascular outcomes in pre-transplant recipients. This study aimed to evaluate the prognostic value of exercise capacity on long-term cardiovascular outcomes in kidney transplant candidates. Methods and Results We retrospectively evaluated exercise capacity in 898 consecutive kidney transplant candidates between 2013 and 2020 who underwent symptom-limited exercise stress echocardiography for pre-transplant cardiovascular assessment. Exercise capacity was measured by age- and sex-predicted metabolic equivalents (METs). The primary outcome was incident major adverse cardiovascular events, defined as cardiac death, non-fatal myocardial infarction, and stroke. Cox proportional hazard multivariable modeling was performed to define major adverse cardiovascular events predictors with transplantation treated as a time-varying covariate. A total of 429 patients (48%) achieved predicted METs. During follow-up, 93 (10%) developed major adverse cardiovascular events and 525 (58%) underwent transplantation. Achievement of predicted METs was independently associated with reduced major adverse cardiovascular events (hazard ratio [HR] 0.49; [95% CI 0.29-0.82], P=0.007), as was transplantation (HR, 0.52; [95% CI 0.30-0.91], P=0.02). Patients achieving predicted METs on pre-transplant exercise stress echocardiography had favorable outcomes that were independent (HR, 0.78; [95% CI 0.32-1.92], P=0.59) and of similar magnitude to subsequent transplantation (HR, 0.97; [95% CI 0.42-2.25], P=0.95). Conclusions Achievement of predicted METs on pre-transplant exercise stress echocardiography confers excellent prognosis independent of and of similar magnitude to subsequent kidney transplantation. Future studies should assess the benefit on exercise training in this population.

Dilatation of the Ascending Aorta in Turner Syndrome: Influence of Bicuspid Aortic Valve Morphology and Body Composition.

BACKGROUND: Aortic dilatation and bicuspid aortic valve (BAV) are frequent in Turner syndrome (TS). Due to short stature, aortic size index (ASI)-ascending aortic diameter (AD)/body surface area (BSA)-is used to identify aortic dilatation in TS patients. We sought to: 1) describe echocardiographic findings in the largest cohort of Australian women with TS; 2) assess if ASI progresses differently with age in TS BAV compared to non-syndromic BAV; and 3) determine whether adjustment of AD for body composition may be superior to BSA indexation. METHODS: Transthoracic echocardiography (TTE) data were retrospectively collected on 125 women with TS. Body composition was quantified by dual energy X-ray absorptiometry (DXA) in 60 women within 6 months of baseline TTE. Age-matched females with non-syndromic BAV (n=170) were used as controls for TS patients with BAV. RESULTS: Mean age of TS women was 28±16 years, and mean height and BSA were 141.6±21.7 cm and 1.4±0.4 m2, respectively. Mean AD was 2.5±0.8 cm, and ASI 2.0±0.6 cm/m2. Aortic dilatation (ASI >2.0 cm/m2) was present in 42 (34%) patients. Turner syndrome women with BAV (n=34; 27%) had a larger ASI than those with tri-leaflet AV (2.2±0.4 cm/m2 vs. 1.7±0.3 cm/m2, p<0.001). In the pooled BAV cohort, TS patients had a higher baseline ASI (2.2±0.4 cm/m2 vs. 2.1±0.3 cm/m2, p=0.02) and greater increase in ASI with age (0.21 mm/m2/year vs. 0.10 mm/m2/year, p=0.01) compared to non-syndromic BAV patients. DXA fat-free mass (r=0.33, p=0.01) and lean mass (r=0.32, p=0.02) correlated with AD, as did BSA (r=0.62, p<0.001). CONCLUSION: Turner syndrome women with BAV have a greater degree of baseline aortic dilatation and a twofold faster increase in aortic dimension with age when compared to matched women with non-syndromic BAV. Several DXA-derived body composition parameters correlate with aortic size in TS, however BSA appears to be the most robust method of indexation.

Relationships of global longitudinal strain with s`, long-axis systolic excursion, left ventricular length and heart rate.

BACKGROUND: Longitudinal left ventricular (LV) contraction can be impaired in the presence of a normal LV ejection fraction (LVEF), and abnormalities have been reported in global longitudinal strain (GLS), long-axis systolic excursion (SExc), and the peak systolic velocity (s`) of mitral annular motion using tissue Doppler imaging (TDI). However, the relationships of GLS with s` and SExc have not been systematically evaluated in subjects with a normal LVEF, and whether these relationships might be affected by variations in LV end-diastolic length (LVEDL) and heart rate is unknown. METHODS: We investigated the univariate and multivariate correlations of GLS with TDI measurements of s` and SExc (both using averages of the septal and lateral walls), LVEDL and heart rate in subjects with a normal LVEF (>50%) but a low peak early diastolic mitral annular velocity (septal e`≤ 7.0 cm/s and lateral e`≤ 9 cm/s), and thus an increased risk of a future cardiac event. RESULTS: 84 subjects (age 66±8 years, 29 males) with a LVEF of 62±6% and GLS of -17.5±2.3% were studied. On univariate analysis the absolute value of GLS was positively correlated with s`(r = 0.28, p<0.01) and SExc (r = 0.50, p<0.001) and inversely correlated with heart rate (r = -0.36, p = 0.001), but was not correlated with LVEDL (r = -0.15). In multivariate models, SExc explained more of the variance in GLS than s`, and absolute GLS was not only positively correlated with SExc, but also inversely correlated with LVEDL. Heart rate was an independent inverse correlate of GLS in conjunction with LVEDL and either s` or SExc, but made a larger contribution in models which included s`. Interobserver correlations were close for s` and SExc (r = 0.89-0.93), but only moderate for GLS (r = 0.71). CONCLUSION: In subjects with a normal LVEF but reduced e`, the absolute value of GLS is more closely related to SExc than s`, and is also independently and inversely related to LVEDL and heart rate. Measurement of SExc may provide a useful additional or alternative technique to GLS for the assessment of LV long-axis function.

Is exercise stress echocardiography useful in patients with suspected obstructive coronary artery disease who have resting left bundle branch block?

BACKGROUND: Current guidelines support exercise stress echocardiography (ESE) for evaluation of suspected obstructive coronary artery disease (OCAD) in ambulant patients with left bundle branch block (LBBB). Data regarding the diagnostic utility of ESE in patients with LBBB are limited. HYPOTHESIS: We hypothesized that the diagnostic performance of ESE for the assessment of suspected OCAD is reduced in the context of LBBB. METHODS: We studied 191 consecutive patients with resting LBBB undergoing ESE for the investigation of suspected OCAD between 2008 and 2015 at our center. The studies were categorized as inconclusive, normal, or abnormal. Patients with an abnormal response were subcategorized as regional ischemic response or globally abnormal. RESULTS: Eighty-two patients (43%) demonstrated a normal left ventricular contractile response (LVCR) to exercise; 92 (48%) developed an abnormal LVCR to exercise, including 70 patients with globally abnormal and 22 patients with regional ischemic responses. Of the patients with abnormal responses, 62 patients had anatomic imaging, only 29 of whom had significant OCAD, conferring an overall specificity of ESE for significant OCAD of 21% and accuracy of 52%. Of patients who developed a regionally abnormal response, 89% had significant OCAD. CONCLUSIONS: For patients with LBBB who develop a globally abnormal LVCR during ESE, the specificity of ESE for reliably excluding significant OCAD is significantly reduced. ESE appears to be a suboptimal test for the evaluation of OCAD in patients with resting LBBB, as about 50% of patients will have an abnormal response, the majority due to globally abnormal contraction where OCAD cannot be reliably diagnosed. Alternative testing should be considered for the investigation of suspected OCAD in patients with resting LBBB.

Imaging Guidance for Transcatheter Aortic Valve Replacement: Is Transoesophageal Echocardiography the Gold Standard?

Transcatheter aortic valve replacement (TAVR) is traditionally performed under cardiac imaging guidance. In the early TAVR experience, intra-procedural transoesophageal echocardiography (TOE) is recommended to guide device deployment, in the context of general anaesthesia (GA). Intra-procedural TOE imaging is particularly useful during TAVR deployment as a contrast-saving strategy for patients with renal impairment. Evidence has emerged recently demonstrating that in selected patients, transthoracic echocardiography (TTE) can be used to provide intra-procedural guidance for TAVR. Additionally, there is a growing body of evidence supporting the performance of TAVR using fluoroscopy alone, without additional cardiac imaging. This article aims to provide a contemporary review of the various procedural imaging approaches for TAVR guidance, comparing the relative strengths and weaknesses of each approach (Table 1).

Possible Mechanisms Underlying Aging-Related Changes in Early Diastolic Filling and Long Axis Motion-Left Ventricular Length and Blood Pressure.

BACKGROUND: The transmitral E wave and the peak velocity of early diastolic mitral annular motion (e`) both decrease with age, but the mechanisms underlying these age-related changes are incompletely understood. This study investigated the possible contributions of blood pressure (BP) and left ventricular end-diastolic length (LVEDL) to age-related reductions in E and e`. METHODS: The study group were 82 healthy adult subjects <55 years of age who were not obese or hypertensive. Transmitral flow and mitral annular motion were recorded using pulsed-wave Doppler. LVEDL was measured from the mitral annular plane to the apical endocardium. RESULTS: Age was positively correlated with diastolic BP and septal wall thickness (SWT), inversely correlated with LVEDL (ß = -0.25) after adjustment for sex and body surface area, but was not related to left ventricular end-diastolic diameter (LVEDD). Age was also inversely correlated with E (r = -0.36), septal e`(r = -0.53) and lateral e`(r = -0.53). On multivariable analysis, E was inversely correlated with diastolic BP and LVEDD, septal e`was inversely correlated with diastolic BP and positively correlated with SWT and LVEDL, after adjusting for body mass index, whilst lateral e`was inversely correlated with diastolic BP and positively correlated with LVEDL. CONCLUSION: The above findings are consistent with higher BP being a contributor to age-related reductions in both E and e`and shortening of LVEDL with age being a contributor to the age-related reduction in e`. An implication of these findings is that slowing of myocyte relaxation is unlikely to be the sole, and may not be the main, mechanism underlying age-related decreases in E and e`.

Feasibility of exercise stress echocardiography for cardiac risk assessment in chronic kidney disease patients prior to renal transplantation.

BACKGROUND: Pharmacologic stress testing is utilized in preference to exercise stress echocardiography (ESE) for cardiac risk evaluation in potential renal transplant recipients due to the perceived lower feasibility of ESE for achieving adequate workload and target heart rate (THR) in this population. METHODS: Consecutive patients referred for cardiac risk evaluation prior to potential kidney transplantation were evaluated. All patients attempted ESE before pharmacologic testing was considered. Treadmill ESE utilized BRUCE protocol to maximum capacity. THR was defined as >85% of the maximum predicted heart rate (220-age). Functional capacity was assessed by metabolic equivalents (METs) and the rate pressure product (RPP). RESULTS: Of 535 patients (349 male, age 56±11), 372(70%) reached THR. Mean METs were 10±3 with 531(99%) achieving ≥4 METs and 87% ≥7 METs. Mean RPP was 25 821±5820 bpm×mm Hg (83% achieving >20 000 bpm×mm Hg). On multivariate analysis, independent predictors of failure to reach THR were rate-control medication and diabetes; failure to reach 7 METs: females, diabetics, age≥65, and previous cardiac disease; failure to reach RPP>20 000: rate-control medication. There were 97% of ESE completed to physiologic endpoints. CONCLUSION: In unselected potential renal transplant candidates, cardiac assessment by ESE is well tolerated, with 9-in-10 exercising to satisfactory functional capacity. ESE should be considered a feasible alternative to pharmacologic testing in this population.

Abnormal left ventricular contractile response to exercise in the absence of obstructive coronary artery disease is associated with resting left ventricular long-axis dysfunction.

BACKGROUND: The etiology of reduced left ventricular (LV) ejection fraction after exercise, without obstructive coronary artery disease or other established causes, is unclear. The aims of this study were to determine whether patients undergoing treadmill stress echocardiography with this abnormal LV contractile response to exercise (LVCRE) without established causes have resting LV long-axis dysfunction or microvascular dysfunction and to determine associations with this abnormal LVCRE. METHODS: Of 5,275 consecutive patients undergoing treadmill stress echocardiography, 1,134 underwent cardiac computed tomography angiography or invasive angiography. Having excluded patients with obstructive coronary artery disease, hypertensive response, submaximal heart rate response, resting LV ejection fraction < 50%, and valvular disease, 110 with "abnormal LVCRE" and 212 with "normal LVCRE" were analyzed. Resting mitral annular velocities were measured to assess LV long-axis function. Myocardial blush grade and corrected Thrombolysis In Myocardial Infarction frame count were determined angiographically to assess microvascular function. RESULTS: Comparing normal LVCRE with abnormal LVCRE, age (mean, 59.7 ± 11.1 vs 61.4 ± 10.0 years), hypertension (53% vs 55%), diabetes (16% vs 20%), and body mass index (mean, 29.1 ± 5.4 vs 29.5 ± 6.4 kg/m(2)) were similar (P > .05). Abnormal LVCRE had reduced resting LV long-axis function with lower septal (mean, 6.1 ± 1.9 vs 7.7 ± 2.2 cm/sec) and lateral (mean, 8.1 ± 2.9 vs 10.4 ± 3.0 cm/sec) e' velocities (P < .001) and larger resting left atrial volumes (mean, 37.3 ± 10.1 vs 31.1 ± 7.2 mL/m(2), P < .001). On multivariate analysis, female gender (odds ratio [OR], 1.21; 95% confidence interval [CI], 1.15-1.99; P < .001), exaggerated chronotropic response (OR, 1.49; 95% CI, 1.09-2.05; P < .001), resting left atrial volume (OR, 2.38; 95% CI, 1.63-3.47; P < .001), and resting lateral e' velocity (OR, 1.70; 95% CI, 1.22-2.49; P = .003) were associated with abnormal LVCRE, but not myocardial blush grade or corrected Thrombolysis In Myocardial Infarction frame count. CONCLUSIONS: An abnormal LVCRE in the absence of established causes is associated with resting LV long-axis dysfunction and is usually seen in women.

Transthoracic echocardiography is still useful in the initial evaluation of patients with suspected infective endocarditis: evaluation of a large cohort at a tertiary referral center.

OBJECTIVES: To examine the sensitivity of contemporary transthoracic echocardiography (TTE) for the detection of vegetation, abscess cavity, or prosthetic valve dehiscence (Vg) in patients with suspected infective endocarditis (IE) and to identify whether a relatively normal initial TTE finding can be effectively used as a rule out test, obviating the need for transesophageal echocardiography (TEE). PATIENTS AND METHODS: We evaluated clinical, microbiological, and echocardiographic data for all patients with suspected IE referred for both TTE and TEE between January 1, 2005, and December 31, 2010. Patients were stratified into 3 groups by baseline TTE findings: negative TTE (native valves with less than or equal to mild regurgitation and no Vg), equivocal TTE (no Vg but prosthetic valve or greater than mild native valvular regurgitation), and positive TTE (Vg detected). RESULTS: We studied 622 consecutive patients (68% male; mean ± SD age, 62 ± 17 years), including 256 with Staphylococcus aureus bacteremia (SAB). The presence of Vg was confirmed by TEE in 141 patients (23%). The TTE had low sensitivity for the detection of Vg (58%). A total of 271 patients (44%) had an initial negative TTE. Of these, TEE demonstrated Vg in only 8 patients (negative predictive value [NPV] of negative TTE, 97%). The negative TTE group included 132 patients with SAB, only 6 of whom had Vg (NPV, 95%). Of 265 patients with equivocal TTE, Vg was demonstrated in 51 (19%). CONCLUSION: In a hospital population with clinically suspected IE, TTE had low sensitivity for the detection of Vg; however, a negative initial TTE was a common finding, with a high NPV, even in the setting of SAB. A TEE may be avoided in many patients with suspected IE.

Transcatheter closure of secundum atrial septal defects: results in patients with large and extreme defects.

BACKGROUND: Transcatheter closure of moderate sized atrial septal defects (ASD) has been demonstrated to be safe and effective. However, the feasibility of transcatheter closure of very large defects is less clear, particularly when an aortic rim of septal tissue is absent. METHODS: The study included patients referred for transcatheter ASD closure with maximal ASD diameter ≥ 20 mm at pre-procedural transoesophageal echocardiography. Patients were grouped according to presence of moderately large (20-29 mm), very large (30-39 mm), or extremely large (≥ 40 mm) ASD size. Procedural success was defined by successful device deployment and absence of complications. RESULTS: Forty-two patients (median age 40 years, range 12-85 years, 76% female) were included in the study. The mean maximal ASD diameter was 29.0 ± 7.4mm. Twenty-three patients had moderately large ASDs (23.0 ± 2.8mm); 13 had very large ASDs (33.1 ± 2.9 mm) and six had extremely large ASDs (41.3 ± 1.6 mm). The aortic rim was absent in 22 patients, and present in 20 patients (4.7 ± 2.9 mm). Transcatheter defect closure was successful in 36 of 42 patients (86%). Procedural success was 100% in the moderately large ASD group, 92% in the very large group but only 17% (one out of six) in the extremely large group. If patients with ASD ≥ 40 mm were excluded (n = 6), the overall success rate was 97%. A single complication (device dislodgement) occurred in a patient with a 42 mm defect and a deficient postero-inferior rim. The presence or absence of an aortic rim of septum did not influence procedural success. CONCLUSION: The vast majority (97%) of large ASDs in the range 20-39 mm can be successfully closed percutaneously with a low or zero complication rate. However, procedural success is poor when attempting closure of extreme defects (≥ 40 mm), regardless of whether an aortic rim of septal tissue or present or absent.

Current and evolving clinical applications of multidetector cardiac CT in assessment of structural heart disease.

Multidetector computed tomography (CT) has an established role in the evaluation of selected patients suspected of having coronary disease; however, in addition to coronary assessment, multidetector CT can be used to evaluate numerous noncoronary structures in the same examination. In particular, the use of multidetector CT to provide pulmonary and cardiac venous anatomic information prior to electrophysiology procedures is well established, and its important role in the periprocedural evaluation of patients undergoing percutaneous procedures, such as transcatheter aortic valve replacement and left atrial appendage device occlusion, is being increasingly recognized. Such advances have resulted in multidetector CT being increasingly used as a complementary imaging technique to echocardiography and magnetic resonance imaging for the comprehensive evaluation of cardiac structure and function in particular clinical situations. This review provides an overview of the noncoronary cardiac structures that can be evaluated with multidetector CT, and outlines the established appropriate clinical uses of multidetector CT in the assessment of structural heart disease, as well as evolving periprocedural clinical applications.

Association of left ventricular motion and central augmentation index in healthy young men.

BACKGROUND: Central blood pressure is a determinant of cardiovascular outcome; however, it can be described by parameters other than systolic and diastolic pressure with central augmentation index (AIx) often utilized. Although generally considered as determined by peripheral pressure wave reflection, not all data are consistent with this interpretation of AIx. We hypothesized that the motion of the heart during systole may influence central pressure waveform morphology, including the AIx. METHOD: We studied the carotid pressure waveform, aortic stiffness and endothelial function in 20 healthy young men (full data available in 19). Arterial stiffness was measured by carotid femoral pulse wave velocity (cfPWV), endothelial function by peripheral arterial plethysmography (PAPl) and central blood pressure waveform by carotid applanation tonometry. Basal cardiac motion was assessed with pulsed wave tissue Doppler imaging of the septal mitral annulus. RESULTS: Carotid AIx decreased after the administration of glyceryl trinitrate by 11.3 ± (sem) 4.6% (P = 0.02); however, time to the inflection point (Ti) did not change. During systolic contraction at both baseline and after glyceryl trinitrate, time to peak annular systolic velocity was directly related to, and always preceded, carotid Ti (R(2) = 0.81; P < 0.01). Carotid Ti and AIx were not related to cfPWV or endothelial function. CONCLUSION: In fit young men, rather than only being a consequence of arterial properties Ti, and therefore central AIx, may be substantially determined by left ventricular systolic function. These findings question the interpretation of central AIx as a measure of pressure wave reflection and aortic stiffness and potentially impact its interpretation in diagnosis and treatment of cardiovascular risk.

Assessment of left ventricular volumes, ejection fraction and regional wall motion with retrospective electrocardiogram triggered 320-detector computed tomography: a comparison with 2D-echocardiography.

Left ventricular (LV) volumes, ejection fraction (LVEF) and regional wall motion (LVRWM) have important treatment and prognostic implications in patients with coronary artery disease. We sought to determine the accuracy of 320-row multidetector computed tomography (MDCT) for the assessment of LV volumes, LVEF and LVRWM, using 2D-echocardiography as the reference standard. We evaluated 50 consecutive patients (mean age 60 ± 14 years, 66% male) who underwent 320-detector MDCT (dose-modulated retrospective electrocardiogram-triggering) and 2D-echocardiography within 14 days for investigation of known or suspected coronary artery disease. Two blinded readers measured LV volumes on MDCT and visually assessed LVRWM with a 3-point scale using a 17-segment model. A separate experienced echocardiologist, blinded to MDCT findings, assessed LVRWM on 2D-echocardiograms and determined LV volumes and LVEF using Simpson's biplane method. 2D-echocardiography served as the reference standard. Mean LVEF was 59 ± 9% (range 26-75%) on 2D-echocardiography and 60 ± 9% (range 27-76%) on MDCT. Using linear regression analysis, MDCT agreed very well with 2D-echocardiography for assessment of LVEDV (r(2) = 0.88; P < 0.001), LVESV (r(2) = 0.95; P < 0.001) and LVEF (r(2) = 0.90; P < 0.001). Mean differences (±standard deviation) of 14 ± 13 ml, 5 ± 7 ml and 1 ± 3% were observed between MDCT and 2D-echocardiography for LVEDV, LVESV and LVEF, respectively. On 2D-echocardiography, 81/850 (9.5%) segments had abnormal LVRWM. Agreement for assessment of LVRWM between 2D-echocardiography and MDCT was excellent (96%, k = 0.76). Accurate assessment of LV volumes, LVEF and LVRWM is feasible with 320-detector MDCT, with MDCT demonstrating slightly larger LV volumes than 2D-echocardiography.

Acute chest pain investigation: utility of cardiac CT angiography in guiding troponin measurement.

PURPOSE: To assess the impact on length of stay and rate of major adverse cardiovascular events of a cardiac computed tomographic (CT) angiography-guided algorithm to examine patients who present to the emergency department (ED) with low- to intermediate-risk chest pain. MATERIALS AND METHODS: The study was approved by the institutional review board, and all patients gave written informed consent. Two hundred three consecutive patients (mean age, 55 years ± 11 [standard deviation]; 123 men) with low- to intermediate-risk ischemic-type chest pain were prospectively enrolled. Patients underwent initial cardiac CT angiography with subsequent treatment determined by reference to findings at cardiac CT angiography; patients without overt plaque were immediately discharged from the hospital, patients with nonobstructive plaque and mild-to-moderate stenoses were discharged after a negative 6-hour troponin level, and patients with severe stenoses were admitted to the hospital. Discharged patients were followed up for a mean of 14.2 months. Additionally, length of stay and safety outcomes among these patients were compared with those in 102 consecutive patients with low- to intermediate-risk chest pain who presented to the ED and underwent a standard of care (SOC) work-up without cardiac CT angiography. One-way analysis of variance with Bonferroni correction was used to compare length of stay between groups. RESULTS: Cardiac CT angiography findings in the 203 patients who underwent cardiac CT angiography were as follows: Sixty-five (32%) patients had no plaque, 107 (53%) had nonobstructive plaque, and 31 (15%) had severe stenoses. At follow-up, there were no deaths or cases of acute coronary syndrome (cardiac CT angiography, 0%, 95% confidence interval [CI]: 0%, 1.85%; SOC, 0%, 95% CI: 0%, 3.63%), and the rate of readmission to the hospital because of chest pain was higher with the SOC approach (9% vs 1%, P = .01). Mean ED length of stay was lower with cardiac CT angiography (6.62 hours ± 0.38 after a single troponin level and 9.15 hours ± 0.30 after serial troponin levels) than with the SOC approach (11.62 hours ± 0.47, P < .001). CONCLUSION: Tailoring troponin measurement to cardiac CT angiography findings is safe and allows early discharge of patients with low- to intermediate-risk chest pain, resulting in reduced length of stay.

Early changes in left ventricular long-axis function in Friedreich ataxia: relation with the FXN gene mutation and cardiac structural change.

OBJECTIVE: Friedreich ataxia (FRDA) is an autosomal recessive condition due to a GAA triplet expansion in the FXN gene that causes increased left ventricular (LV) wall thickness and can progress to LV systolic dysfunction. However, the changes in myocardial function that occur before a reduction in LV ejection fraction are incompletely understood. METHODS: LV long-axis function was assessed by measurement of tissue Doppler imaging (TDI) peak systolic (S`), early diastolic (E`), and atrial velocities (A`) at the septal and lateral borders of the mitral annulus in 60 subjects homozygous for a GAA expansion in the FXN gene who had preserved LV ejection fraction. Comparison was made with 60 sex- and age-matched controls. TDI velocities at 5 years were compared with baseline values in 17 FRDA subjects with follow-up studies who still had preserved ejection fraction. RESULTS: S` and E` were reduced in FRDA subjects at both the septal and the lateral mitral annular borders. Lateral E` was independently and inversely related to age, blood pressure, septal wall thickness, and the number of GAA repeats in the smaller allele of the FXN gene, whereas septal E` was not correlated with GAA repeat number. At 5 years, there was a reduction in lateral S` and E` but no change in septal TDI velocities. CONCLUSION: Subjects with FRDA have impairment of septal and lateral long-axis LV function, but there also seem to be regional differences in the effects of this condition that are at least partly related to the degree of genetic abnormality.