Normal Left Ventricular Wall Motion Research Articles

Abstract 11458: Temporal Changes in Mitral Regurgitation After Percutaneous Mitral Valve Repair with MitraClip for Functional Mitral Regurgitation in Patients with Atrial Fibrillation

Background: Recently, percutaneous mitral valve (MV) repair has been increasingly performed for functional mitral regurgitation (FMR). However, few studies have examined the effectiveness of percutaneous MV repair for atrial FMR (AFMR). The aim of this study is to compare the effectiveness of MitraClip implantation between patients with AFMR and ventricular FMR (VFMR). Methods: We retrospectively reviewed 113 grade 3 to 4+ FMR patients with persistent atrial fibrillation or atrial flutter who underwent MitraClip implantation. We classified the patients into 2 groups; 43 patients with preserved left ventricular (LV) ejection fraction (LVEF) ≥ 50% and normal LV wall motion were defined as AFMR. 70 patients with LV dysfunction (LVEF < 50 %) or LV wall motion abnormality were defined as VFMR. Transthoracic echocardiography (TTE) follow-up was performed at approximately 1-day, 1-month and 1-year after the procedure. Results: The percentage of grade 4+ mitral regurgitation (MR) was 53% in AFMR and 49% in VFMR at baseline (P=0.61). Acute procedural success rate was similar between AFMR and VFMR (95.3% vs. 97.1%, P=0.49). The median period of 1-month and 1-year follow-up TTE were 33 [interquartile range (IQR): 28-36] days and 356 (IQR: 248-399) days in AFMR, and 34 (IQR: 30-38) days and 366 (IQR: 336-415) days in VFMR, respectively. The percentage of grade 3 or 4+ MR at 1-day, 1-month, and 1-year after the procedure were 4.7% (2/43), 10% (3/30), and 5.6% (1/18) in AFMR, and 2.9% (2/70), 7.3% (4/55), and 2.9% (1/35) in VFMR (P=0.49, 0.48, and 0.57, respectively, AFMR vs. VFMR at the same follow-up point). The rates of redo MitraClip or MV surgery for recurrent MR within 1-month and between 1-month/1-year were 0% and 9.3% in AFMR, and 1.4% and 1.4% in VFMR. The percentage of New York Heart Association functional class III or IV at baseline, 1-month, and 1-year after the procedure were 90.7% (39/43), 23.3% (7/30), and 33.3% (6/18) in AFMR and 97.1% (68/70), 27.3% (15/55), and 22.9% (8/35) in VFMR (P=0.15, 0.69, and 0.41, respectively, AFMR vs. VFMR at the same follow-up point). Conclusions: In our series, MitraClip implantation had comparable therapeutic effect on both MR severity and heart failure symptoms between patients with AFMR and VFMR.

Differences in mitral valve geometry between atrial and ventricular functional mitral regurgitation in patients with atrial fibrillation: a 3D transoesophageal echocardiography study.

This study investigated geometric differences in mitral valve apparatus between atrial functional mitral regurgitation (A-FMR) and functional mitral regurgitation (FMR) with left ventricular (LV) dysfunction in patients with atrial fibrillation (AF) using 3D transoesophageal echocardiography (TOE). In total, 135 moderate or greater FMR patients with persistent AF or atrial flutter underwent 3D TOE. Fifty-six patients had A-FMR, defined as preserved LV ejection fraction (LVEF) of ≥50% and normal LV wall motion. Seventy-nine patients had ventricular FMR (V-FMR), defined as LV dysfunction (LVEF of <50%) or LV wall motion abnormality. To evaluate mitral leaflet coaptation, the coapted area was calculated as follows: total leaflet area (TLA) in end-diastole - closed leaflet area in mid-systole. Although annular area (AA) did not significantly differ between the two groups, TLA was significantly smaller in A-FMR than in V-FMR (P = 0.005). TLA/AA, indicating the degree of the leaflet remodelling, was significantly smaller in A-FMR than in V-FMR (P < 0.001). A-FMR had significantly smaller posterior mitral leaflet tethering height and angle measured at three anteroposterior planes (lateral, central, and medial) than V-FMR (all P < 0.001). However, vena contracta width (VCW) measured on long-axis view on TOE and coapted area, which correlated with VCW (r = -0.464, P < 0.001), were similar between the two groups. Mitral leaflet remodelling may be less in A-FMR compared with V-FMR. However, leaflet tethering was smaller in A-FMR than in V-FMR, and this may result in a similar degree of mitral leaflet coaptation and mitral regurgitation severity.

Reverse redistribution-like change on dipyridamole-stress 99mTc-tetrofosmin imaging in a patient with angiographically mild coronary artery stenosis

A 50-year-old man with a 1-month history of chest pain presented to our hospital. Transthoracic echocardiography showed normal left ventricular wall motion. Coronary computed tomography angiography revealed a mild stenosis with low-density non-calcified plaque in the proximal left anterior descending coronary artery (LAD) (Figure 1A, yellow arrows); therefore, the patient underwent a 1-day protocol of dipyridamole stress and rest 99mTc-tetrofosmin myocardial perfusion imaging (MPI). Baseline electrocardiography was normal; however, he developed angina 8 minutes after the start of .56 mg·kg−1 (.14 mg·kg−1·min−1 for 4 minutes) of intravenous dipyridamole infusion and his electrocardiogram showed ST-segment elevation in the precordial leads (Figure 2). After intravenous aminophylline with sublingual nitroglycerin was given, the ST-segment elevation was gradually resolved. Stress MPI showed no perfusion defect (Figure 1B) with abnormal wall motion in the anterior and septal walls on gated MPI (Supplementary Material). He had recurrent angina after the stress MPI. Rest MPI at 2 hours after the stress test showed reverse redistribution-like reduced uptake in the LAD territory (Figure 1B) with normal left ventricular wall motion on gated MPI (Supplementary Material). As with the coronary computed tomography, invasive coronary angiography via the right radial artery demonstrated the mild stenosis in the proximal LAD (Figure 3, yellow arrow). Intravascular ultrasound and optical coherence tomography images showed coronary plaque with neovascularization (Figure 3, red arrows) and small thrombi (Figure 3, white arrows) at the minimum lumen area site, indicating the increased vulnerability of the coronary plaque.1 Percutaneous coronary intervention (PCI) with a drug-eluting stent (4.0 × 33 mm) was successfully performed (Figure 3, red arrows). On the day following the PCI, he underwent cardiopulmonary exercise testing and did not present with chest pain at peak exercise (VO2 at peak was 22.5 mL·kg−1·min−1 [6.4 METs]). Open in a separate window Figure 1 (A) Coronary computed tomography angiography revealed a mild stenosis (yellow arrows) with low-density non-calcified plaque in the proximal left anterior descending coronary artery (LAD). (B) Dipyridamole stress and rest 99mTc-tetrofosmin myocardial perfusion imaging (MPI). Stress MPI (300 MBq of 99mTc-tetrofosmin) showed no perfusion defect, whereas rest MPI (900 MBq of 99mTc-tetrofosmin) 2 hours after the stress test showed reduced uptake (reverse redistribution) in the LAD territory

Value of territorial work efficiency estimation in non-ST-segment-elevation acute coronary syndrome: a study with non-invasive left ventricular pressure-strain loops.

Non-ST-segment-elevation acute coronary syndrome (NSTE-ACS) patients with normal left ventricular (LV) ejection fraction (LVEF) and wall motion require a non-invasive tool to detect LV risk areas. This study utilized non-invasive LV pressure-strain loops to evaluate territorial myocardial work efficiency (WE) for identifying obstructive coronary artery stenosis, in patients with non-obstructive or obstructive coronary artery stenosis NSTE-ACS, the latter with or without occlusion. Global and territorial longitudinal strain (LS) analyses were performed via speckle-tracking imaging before coronary angiography. LV pressure-strain loops estimated global and territorial myocardial work index (MWI), constructive work (CW), wasted work (WW), and WE. Receiver operating characteristic curve analysis was used to determine the optimal cutoff value of independent parameters to detect obstructive coronary artery stenosis. Compared with non-obstructive, obstructive coronary artery stenosis showed significantly lower global and territorial LS, MWI, CW, and WE, and higher WW. Territorial LS, MWI, CW, and WE were significantly worse in territories of coronary occlusion. Territorial WE was the best parameter for predicting obstructive coronary artery stenosis (AUC 0.80, cutoff < 96%, sensitivity 73%, specificity 70%, P < 0.001). In patients with NSTE-ACS with normal wall motion and LVEF, territorial WE is more accurate than territorial LS or MWI to identify LV risk areas.

Impaired global longitudinal strain in elderly patients with preserved ejection fraction is associated with raised post-exercise left ventricular filling pressure.

The purpose of this study was to evaluate whether impaired resting global longitudinal strain (GLS) in elderly patients with preserved left ventricular (LV) ejection fraction (EF) is associated with raised post-exercise LV filling pressure estimated by the ratio of early diastolic transmitral flow velocity to annulus velocity (E/e'). Seventy elderly patients (age = 74 ± 6years, male 40 patients) who underwent treadmill stress echocardiography were studied. All patients had normal sinus rhythm, normal LV wall motion at rest, and had preserved LVEF ≥ 50%. Patients with exercise induced wall motion abnormality were not included. GLS at rest was measured using automated functional imaging. Twenty-four of the 70 patients had raised post-exercise LV filling pressure indicated by septal E/e' ≥ 15.0. Patients with raised post-exercise LV filling pressure had smaller resting GLS than that in patients without it (-16.9 ± 1.8 vs. -19.6 ± 2.5%, respectively, p < 0.0001). Downward stepwise multivariate logistic regression analysis demonstrated that resting GLS was one of independent predictors of raised post-exercise E/e'. Receiver operating characteristic (ROC) curve analysis had demonstrated that optimal cutoff point for resting GLS to predict raised post-exercise E/e' was -17.8% (sensitivity 83.3%, specificity 80.4%, respectively), and the area under the ROC curve was 0.820. In elderly patients with preserved LVEF and without obvious myocardial ischemia, impaired resting GLS at rest is associated with raised post-exercise LV filling pressure estimated by E/e' ≥ 15.0.

A Clinical Tool to Identify Candidates for Stress-First Myocardial Perfusion Imaging

ObjectivesThis study sought to develop a clinical model that identifies a lower-risk population for coronary artery disease that could benefit from stress-first myocardial perfusion imaging (MPI) protocols and that can be used at point of care to risk stratify patients. BackgroundThere is an increasing interest in stress-first and stress-only imaging to reduce patient radiation exposure and improve patient workflow and experience. MethodsA secondary analysis was conducted on a single-center cohort of patients undergoing single-photon emission computed tomography (SPECT) and positron emission tomography (PET) studies. Normal MPI was defined by the absence of perfusion abnormalities and other ischemic markers and the presence of normal left ventricular wall motion and left ventricular ejection fraction. A model was derived using a cohort of 18,389 consecutive patients who underwent SPECT and was validated in a separate cohort of patients who underwent SPECT (n = 5,819), 1 internal cohort of patients who underwent PET (n=4,631), and 1 external PET cohort (n = 7,028). ResultsFinal models were made for men and women and consisted of 9 variables including age, smoking, hypertension, diabetes, dyslipidemia, typical angina, prior percutaneous coronary intervention, prior coronary artery bypass graft, and prior myocardial infarction. Patients with a score ≤1 were stratified as low risk. The model was robust with areas under the curve of 0.684 (95% confidence interval [CI]: 0.674 to 0.694) and 0.681 (95% CI: 0.666 to 0.696) in the derivation cohort, 0.745 (95% CI: 0.728 to 0.762) and 0.701 (95% CI: 0.673 to 0.728) in the SPECT validation cohort, 0.672 (95% CI: 0.649 to 0.696) and 0.686 (95% CI: 0.663 to 0.710) in the internal PET validation cohort, and 0.756 (95% CI: 0.740 to 0.772) and 0.737 (95% CI: 0.716 to 0.757) in the external PET validation cohort in men and women, respectively. Men and women who scored ≤1 had negative likelihood ratios of 0.48 and 0.52, respectively. ConclusionsA novel model, based on easily obtained clinical variables, is proposed to identify patients with low probability of having abnormal MPI results. This point-of-care tool may be used to identify a population that might qualify for stress-first MPI protocols.

Abnormal left ventricular global strain during exercise-test in young healthy smokers

Background. It is unknown how much precociously the cigarette smoking (CS) may compromise the integrity of the cardiovascular (CV) system. Myocardial function can be routinely assessed by conventional echocardiography, but abnormalities are only detected when somewhat a remodelling has already occurred. These limitations could be overcome by strain imaging. Methods. We evaluated whether young smokers with normal left ventricular (LV) geometry, wall motion and ejection fraction may present abnormalities in myocardial deformation, both at rest and during physical effort. We selected 50 young smokers with no additional CV risk factors, and 60 non-smokers to undergo a standardized exercise-test. Consistently, we evaluated the CV adaptation to exercise by both conventional echocardiography and speckle-tracking analysis (2D-STE). Results. We found no difference between smokers and controls regarding baseline characteristics; as expected, smokers presented with lower HDL-cholesterol (p < 0.005), and higher fibrinogen, C-reactive protein (CRP), and interleukin-6 (p < 0.001). Conventional echocardiography parameters were not different between groups, while we detected a different behaviour of global longitudinal strain (GLS), global circumferential strain (GCS) and twist by 2D-STE during exercise-test. Indeed, GLS, GCS and twist behaved differently during exercise test in smokers with respect to controls. We found an association between CS, inflammation and LV mechanics changes uncovered by physical effort, and regression analysis confirmed that the intensity of the exposure to cigarette smoking, together with the inflammatory status (CRP, fibrinogen and Il-6) plasma levels, drive this impairment. Conclusions. We confirm strain imaging (2D-STE) as a very useful tool to identify early changes in cardiac mechanics, as adaptation to exercise; our findings may reflect a very precocious functional abnormality in active smokers, likely long before structural damage occurs.

Global Myocardial Work Is Superior to Global Longitudinal Strain to Predict Significant Coronary Artery Disease in Patients With Normal Left Ventricular Function and Wall Motion

Noninvasive detection of functionally significant coronary artery disease (CAD) by echocardiography remains challenging, with the need to perform stress imaging to detect ischemia. The aim of this study was to determine whether global myocardial work (MW), derived from noninvasive left ventricular (LV) pressure-strain loops at rest, can predict significant CAD in patients without regional wall motion abnormalities and preserved LV ejection fraction (EF). One hundred and fifteen patients referred for coronary angiography who had EF≥55%, no resting regional wall motion abnormalities, and no chest pain were assessed using echocardiography. Global MW was derived from noninvasive LV pressure-strain loops constructed from speckle-tracking echocardiography indexed to brachial systolic blood pressure. Global constructive work represented the sum of positive work due to myocardial shortening during systole and negative work due to lengthening during isovolumic relaxation. Global wasted work represented energy loss by myocardial lengthening in systole and shortening in isovolumic relaxation. Global MW efficiency was derived from the percentage ratio of constructive work to the sum of constructive work and wasted work. Patients with significant CAD demonstrated a significantly reduced global MW (P<.001) compared with those without CAD. Global longitudinal strain was significantly reduced (P<.001) in patients with multivessel CAD but not those with single-vessel CAD (P=.47). Receiver operating characteristic curve analysis demonstrated that global MW was the most powerful predictor of significant CAD (area under the curve=0.786) and was superior to global longitudinal strain (area under the curve=0.693). The optimal cutoff global MW value to predict significant CAD was 1,810mm Hg% (sensitivity, 92%; specificity, 51%). Noninvasive global MW derived using LV pressure-strain loops at rest is a more sensitive index than global longitudinal strain to detect significant CAD in patients with no regional wall motion abnormalities and normal EF. This is a potential valuable clinical tool to assist in the early diagnosis of CAD.

Layer-specific strain analysis in patients with suspected stable angina pectoris and apparently normal left ventricular wall motion

BackgroundNon-invasive imaging tests are widely used in the evaluation of stable angina pectoris (SAP). Despite these tests, non-significant coronary lesions are not a rare finding in patients undergoing elective coronary angiography (CAG). Two-dimensional (2D) speckle tracking global longitudinal strain (GLS) imaging is a more sensitive and accurate technique for measuring LV function than conventional 2D methods. Layer-specific strain analysis is a relatively new method that provides endocardial and epicardial myocardial layer assessment. The aim of the present study was to evaluate longitudinal layer-specific strain (LSS) imaging in patients with suspected SAP.MethodsPatients who underwent CAG for SAP were retrospectively screened. A total of 79 patients with no history of heart disease and wall motion abnormalities were included in the study. Forty-three patients with coronary lesions > 70% constituted the coronary artery disease (CAD) group and 36 patients without significant CAD constituted the control group. Layer-specific GLS transmural, endocardium, and epicardium values (GLS-trans, GLS-endo, and GLS-epi, respectively) were compared between the groups.ResultsPatients in the CAD group had significantly lower GLS values in all layers (GLS-trans: -18.2 + 2.4% vs -22.2 + 2.2% p < .001; GLS-endo: -20.8 + 2.8% vs -25.3 + 2.6%, p < .001; GLS-epi: 15.9 + 2.4% vs -19.5 + 1.9%, p < .001). Multivariate adjustment demonstrated GLS-trans as the only independent predictor of CAD [OR:0.472, CI (0.326–0.684), p < .001]. Additionally, the GLS values were all lower in myocardial perfusion scintigraphy (MPS) true-positive patients compared with MPS false-positive patients (GLS-trans: -17.7 ± 2.4 vs. -21.9 ± 2.4%, p < .001; GLS-endo: -20.2 ± 2.9% vs -24.9 ± 2.9%, P < .001; GLS-epi: 15.4 ± 2.6% vs. -19.2 ± 1.8%, P < .001).ConclusionResting layer-specific strain as assessed by 2D speckle tracking analysis demonstrated that GLS values were reduced in all layers of myocardium with SAP and with no wall motion abnormalities. LSS analysis can improve the identification of patients with significant CAD but further prospective larger scale studies are needed to put forth the incremental value of LSS analysis over transmural GLS.

Myocardial Work Using Non–Invasive Pressure Strain Loops can Predict Severe Coronary Artery Stenosis in Patients with Normal Left Ventricular Wall Motion: Insights from the CATHARSIS Trial

Myocardial Work Using Non–Invasive Pressure Strain Loops can Predict Severe Coronary Artery Stenosis in Patients with Normal Left Ventricular Wall Motion: Insights from the CATHARSIS Trial

St-Elevation Acute Myocardial Infarction Due to Arterial Thrombosis in a 29-Year-Old Woman with Normal Coronary Arteries

Acute myocardial infarction (AMI) is rare in young adults. We present a case of a 29-year-old black woman who presented with an acute onset of chest pain while sleeping. Anterior wall ST-elevation AMI was diagnosed based on clinical presentation, electrocardiographic findings, and elevated cardiac biomarkers. Coronary angiography revealed a totally occluded proximal left anterior descending artery. The obstructing lesion, thrombus, was removed. There was no evidence of atherosclerotic disease or dissection. An evaluation for a hypercoagulable state was unrevealing. Echocardiography 1 year later revealed normal left ventricular wall motion and systolic function.

Sarcomatoid Carcinoma of the Liver

An 86-year-old man with a remote history of colon cancer was admitted to medicine with fever, cough, dyspnea, malaise, and weight loss. A surveillance colonoscopy was negative within the year. He had been admitted 1 week prior for pneumonia and treated with a 7-day course of ceftriaxone and azithromycin. He denied improvement after the previous antibiotic course and described worsening dyspnea and lower extremity edema. His admission labs revealed mildly elevated ProBNP, positive influenza A PCR nasal swab, and AST/ALT/ALP/Albumin of 123/59/338/2, respectively Chest X-ray revealed worsening pulmonary vascular congestion and increasing right pleural effusion. He was started on Lasix and Tamiflu. Echocardiogram showed normal left ventricular ejection fraction and wall motion. Despite treatment for presumed diastolic heart failure with aggressive diuresis and supportive care for influenza A, the patient remained edematous and listless without clinical improvement. Lower extremity venous duplex revealed a deep venous thrombosis in the soleal vein although a follow up lung ventilation-perfusion scan was indeterminate. Liver tests were re-assessed and returned 31/43/126/1.7. Abdominal ultrasonography revealed a large heterogeneous mass occupying most of the posterior and inferior portion of the right liver lobe measuring 22 x 13 x 14 cm. On the evening after the ultrasound examination, the patient suffered a cardiac arrest after a possible aspiration event. Despite full ACLS protocol, return of spontaneous circulation was not achieved and the patient was pronounced dead.Figure 1Post-mortem examination showed metastatic high grade sarcomatoid carcinoma found throughout the splenic capsule, lungs, colon, gallbladder and mesentery with the most significant lesion found in the liver measuring 18 cm in greatest dimension.Figure 2Figure 3Sarcomatoid carcinoma of the liver is rare tumor, composing 0.2% of primary hepatic malignancies, but arising more frequently in those with Hepatitis B, and cirrhosis. It is a highly aggressive tumor with poor prognosis and high rates of recurrence after resection. Diagnosis currently is dependent on tissue biopsy and typical histopathologic findings of malignant spindle cells and supportive immunohistochemical staining of vimentin, and epithelial membrane antigen and liver tumor markers HePar.

Presence of Postsystolic Shortening Increases the Likelihood of Coronary Artery Disease: A Rest Electrocardiography-Gated Myocardial Perfusion SPECT Study

Postsystolic shortening (PSS), which is a delayed myocardial contraction that occurs after end-systole, has been considered an important diagnostic index of myocardial ischemia. Recent technological advancements in quantitative gated SPECT (QGS) software enables the left ventricular (LV) regional analysis and may be useful for PSS measurement. The purpose of this study was to evaluate whether PSS at the resting condition determined by QGS is useful to identify patients with coronary artery disease. The study comprised 146 patients (mean age ± SD, 71 ± 8 y; 98 men) with normal LV wall motion (mean LV ejection fraction ± SD, 72% ± 9%) who underwent both coronary angiography and resting (99m)Tc-tetrofosmin myocardial perfusion SPECT. The sum of the difference between post-end-systolic maximal LV thickening and end-systolic LV thickening, designated PSS index, was calculated from 17 LV myocardial segments using QGS. The PSS index was significantly higher in patients with significant stenosis of the coronary artery than in the other patients (9.8 ± 10.2 vs. 5.6 ± 5.1; P < 0.01). A cutoff point of 6.0 of the PSS index had sensitivity, specificity, positive predictive value, and negative predictive values of 55%, 70%, 76%, and 47%, respectively, for the diagnosis of coronary artery disease. Multivariate logistic regression analysis demonstrated that a PSS index greater than 6.0 was an independent predictor for the presence of coronary artery disease (odds ratio, 2.46; 95% confidence interval, 1.1-5.4; P < 0.05). Among subjects with normal LV function, PSS index even in the resting condition determined using QGS may help to identify patients with coronary artery disease.

Stress-induced Cardiomyopathy Precipitated by Triathlon Competition: A Case Report

Stress-induced cardiomyopathy in post-menopausal women is transient and typically precipitated by severe emotional or physical stress. We report a rare case of stressinduced cardiomyopathy mimicking acute coronary syndrome in a middle-aged female triathlete. The initial presentation included chest tightness and dyspnea; however, acute pulmonary edema and cardiogenic shock developed shortly after admission. Electrocardiography showed non-specific ST-T changes and echocardiography revealed severe left ventricular dysfunction with regional wall motion abnormalities. Coronary angiography did not reveal significant coronary artery obstruction. The patient was placed on ventilatory support and administered diuretics and an angiotensin-converting enzyme inhibitor. Follow-up echocardiography on day 3 showed nearly normal left ventricular wall motion with a 54% ejection fraction, and follow-up radiography of the chest revealed no evidence of pulmonary edema. The endotracheal tube was removed on the third day of hospitalization and the patient was discharged two days later without complications.

Low diastolic wall strain is associated with raised post-exercise E/E' ratio in elderly patients without obvious myocardial ischemia.

It has been reported that the diastolic wall strain (DWS) inversely correlates with the myocardial stiffness constant. The ratio of early diastolic transmitral flow velocity to annulus velocity (E/E') correlates with the left ventricular (LV) filling pressure. Increased LV wall stiffness is thought be associated with increased LV filling pressure after exercise. The purpose of this study was to evaluate the correlation between the DWS and post-exercise E/E' in elderly patients without obvious myocardial ischemia. Fifty-eight elderly patients (age=74±6years) who underwent treadmill stress echocardiography were studied. All patients had normal LV wall motion at rest, and patients with exercise-induced wall motion abnormality were excluded. The DWS was calculated as follows: DWS=(PWTs-PWTd)/PWTs, where PWTs is the LV posterior wall thickness at end-systole and PWTd is that at end-diastole. As previously reported, DWS≤0.33 was defined as low DWS and E/E' ≥15.0 was defined as a marker of increased LV filling pressure. Eighteen patients had low DWS. Patients with low DWS had greater post-exercise E/E' (17.9±3.2 vs. 12.8±3.3, p<0.0001). The DWS was inversely and strongly correlated with post-exercise E/E' (r (2)=0.534, p<0.0001). Low DWS predicted the development of raised post-exercise E/E' ≥15.0 with a positive predictive value of 94% and a negative predictive value of 85%. In elderly patients without obvious myocardial ischemia, the DWS correlates strongly and inversely with post-exercise E/E'. Patients with low DWS were likely to develop raised E/E' after exercise.

Association of low-grade albuminuria with adverse cardiac mechanics: findings from the hypertension genetic epidemiology network (HyperGEN) study.

Albuminuria is a marker of endothelial dysfunction and has been associated with adverse cardiovascular outcomes. The reasons for this association are unclear but may be attributable to the relationship between endothelial dysfunction and intrinsic myocardial dysfunction. In the Hypertension Genetic Epidemiology Network (HyperGEN) Study, a population- and family-based study of hypertension, we examined the relationship between urine albumin-to-creatinine ratio (UACR) and cardiac mechanics (n=1894, all of whom had normal left ventricular ejection fraction and wall motion). We performed speckle-tracking echocardiographic analysis to quantify global longitudinal, circumferential, and radial strain, and early diastolic (e') tissue velocities. We used E/e' ratio as a marker of increased left ventricular filling pressures. We used multivariable-adjusted linear mixed effect models to determine independent associations between UACR and cardiac mechanics. The mean age was 50±14 years, 59% were female, and 46% were black. Comorbidities were increasingly prevalent among higher UACR quartiles. Albuminuria was associated with global longitudinal strain, global circumferential strain, global radial strain, e' velocity, and E/e' ratio on unadjusted analyses. After adjustment for covariates, UACR was independently associated with lower absolute global longitudinal strain (multivariable-adjusted mean global longitudinal strain [95% confidence interval] for UACR Quartile 1 = 15.3 [15.0-15.5]% versus UACR Q4 = 14.6 [14.3-14.9]%, P for trend <0.001) and increased E/e' ratio (Q1 = 25.3 [23.5-27.1] versus Q4 = 29.0 [27.0-31.0], P=0.003). The association between UACR and global longitudinal strain was present even in participants with UACR < 30 mg/g (P<0.001 after multivariable adjustment). Albuminuria, even at low levels, is associated with adverse cardiac mechanics and higher E/e' ratio.

ASSOCIATION OF ALBUMINURIA WITH ADVERSE CARDIAC MECHANICS: FINDINGS FROM THE HYPERGEN STUDY

Background —Albuminuria is a marker of endothelial dysfunction and has been associated with adverse cardiovascular outcomes. The reasons for this association are unclear, but may be due to the relationship between endothelial dysfunction and intrinsic myocardial dysfunction. Methods and Results —In the HyperGEN study, a population- and family-based study of hypertension, we examined the relationship between urine albumin-to-creatinine ratio (UACR) and cardiac mechanics (N=1894, all of whom had normal left ventricular ejection fraction and wall motion). We performed speckle-tracking echocardiographic analysis to quantify global longitudinal, circumferential, and radial strain (GLS, GCS, and GRS, respectively), and early diastolic (e') tissue velocities. We used E/e' ratio as a marker of increased LV filling pressures. We used multivariable-adjusted linear mixed effect models to determine independent associations between UACR and cardiac mechanics. The mean age was 50±14 years, 59% were female, and 46% were African-American. Comorbidities were increasingly prevalent among higher UACR quartiles. Albuminuria was associated with GLS, GCS, GRS, e' velocity, and E/e' ratio on unadjusted analyses. After adjustment for covariates, UACR was independently associated with lower absolute GLS (multivariable-adjusted mean GLS [95% CI] for UACR Quartile 1 = 15.3 [15.0-15.5]% vs. UACR Q4 = 14.6 [14.3-14.9]%, P for trend <0.001) and increased E/e' ratio (Q1 = 25.3 [23.5-27.1] vs. Q4 = 29.0 [27.0-31.0], P= 0.003). The association between UACR and GLS was present even in participants with UACR < 30 mg/g (P<0.001 after multivariable adjustment). Conclusions —Albuminuria, even at low levels, is associated with adverse cardiac mechanics and higher E/e' ratio.

Prediction of Coronary Artery Stenosis at Rest in Patients With Normal Left Ventricular Wall Motion

Noninvasive detection of coronary artery stenosis usually requires a stress test in patients without left ventricular (LV) regional wall motion abnormalities (RWMA). In contrast, abnormal regional LV relaxation caused by ischemia may persist beyond recovery from transient ischemia. The aim of the present study was to determine whether segmental analysis of abnormal regional LV relaxation using the strain imaging diastolic index (SI-DI) at rest could predict coronary artery stenosis in the three major vessels in patients without LV dysfunction or RWMA. We performed 2D speckle tracking echocardiography and coronary angiography in 85 patients without RWMA with suspected coronary artery disease. Patients with LV dysfunction or acute coronary syndrome were excluded. Echocardiographic images of the LV were obtained in the apical 2-, 3-, and 4-chamber views and divided into 6 segments. In each segment, SI-DI derived from transverse strain imaging was determined. Forty-eight patients had significant coronary artery stenosis (≥ 70%). The optimal cutoff values of SI-DI were 60.5% in the mid anteroseptal segment for detecting left anterior descending artery stenosis (sensitivity, 83.3%; specificity, 81.1%), 60.5% in the basal anterolateral segment for detecting left circumflex artery stenosis (sensitivity, 80.9%; specificity, 90.3%), and 61.5% in the basal inferior segment for detecting right coronary artery stenosis (sensitivity, 74.1%; specificity, 77.8%). A segmental analysis of SI-DI at rest predicted coronary artery stenosis in the three major vessels in patients without RWMA. This noninvasive method may be useful for detecting coronary artery stenosis without a stress test.

Abstract 19085: Cross-bridge Activation at Diastolic Calcium Levels in Human Myocardium

Tropomyosin is positioned on actin in dynamic equilibrium as a function of free calcium concentration. However, it is estimated that ∼5% of the myosin binding sites on actin are exposed at low calcium levels (e.g. pCa 8) raising the possibility of myosin cross-bridge formation at diastolic calcium levels. We tested this hypothesis in detergent-treated (skinned) strips dissected from epicardial biopsies obtained from male patients during coronary bypass grafting. Patients (n=15) had normal left ventricular (LV) ejection fraction and wall motion. Eight control (C) patients had neither hypertension (HTN) nor diabetes mellitus. Seven patients had HTN and concentric remodeling with increased LV wall thickness/radius ratio. Western blot analysis of skinning supernatant revealed no loss of tropomyosin or troponin-I that would implicate loss of normal thin filament regulation during the skinning process. Myofilament calcium sensitivity at sarcomere length 2.2 μm was similar between C and HTN (pCa 50 6.07±0.07 vs 6.06±0.04). Tension at pCa 8 was similar between C and HTN (4.26±0.52 vs 4.30±0.51 mN.mm -2 ), but was significantly reduced by application the cross-bridge inhibitor 2,3-butanedione monoximine (BDM) (2.15±0.24 vs 3.01±0.40 mN.mm -2 , p&lt;0.05). The higher tension in HTN with BDM reflects a greater inherent stiffness in HTN independent of cross-bridges. We then used sinusoidal length perturbations (0.125-250 Hz) to detect the detachment rate of cycling cross-bridges. In both C and HTN strips, frequency-dependent viscoelastic characteristics of cycling cross-bridges were apparent at pCa 8 and abolished with BDM. At pCa 8 cross-bridge detachment rate was significantly greater in C than HTN (106.1±12.5 vs 74.6±9.3 s -1 , p&lt;0.05). These results indicate that there are cycling cross-bridges in normal and concentrically remodeled human myocardium at diastolic calcium levels that contribute to diastolic tension. Furthermore, the rate of cross-bridge detachment under relaxed conditions is slower in concentrically remodeled myocardium from HTN compared with C patients. The presence and lifetime of cross-bridges formed in addition to cross-bridge independent stiffness must be considered as significant contributors to diastolic dysfunction in HTN.

Myosin Cross-Bridge Dynamics in Patients With Hypertension and Concentric Left Ventricular Remodeling

Hypertension (HTN) causes concentric left ventricular remodeling, defined as an increased relative wall thickness or overt left ventricular hypertrophy, and associated diastolic dysfunction. HTN and concentric remodeling are also common precursors to heart failure with a preserved ejection fraction. It is not known whether the myofilament contributes to diastolic dysfunction in patients with concentric remodeling. Intraoperative myocardial biopsies were obtained in 15 male patients undergoing coronary bypass grafting, all with normal left ventricular ejection fraction and wall motion. Eight patients had a history of HTN and concentric remodeling. Seven without HTN or remodeling served as controls. Myocardial strips were dissected and demembranated with detergent. Isometric tension was measured and sinusoidal length perturbation analysis performed at sarcomere length 2.2 μm and pCa 8 to 4.5. Sinusoidal analysis provides estimates of cross-bridge dynamics, including rate constants of attachment and detachment and cross-bridge attachment time. The normalized isometric tension-pCa relation was similar in HTN and controls. However, cross-bridge attachment time was significantly prolonged at submaximal [Ca(2+)] (pCa ≥6.5) in HTN patients. Analysis of protein phosphorylation revealed ≈25% reduction in phosphorylation of troponin I in HTN patients (P<0.05). Compared with controls, patients with HTN and concentric remodeling display prolonged cross-bridge attachment time at submaximal [Ca(2+)] without a change in the tension-pCa relation. Prolonged cross-bridge attachment time implicates altered cross-bridge dynamics as a cause of slowed relaxation in these patients. This finding was associated with reduced phosphorylation of troponin I, suggesting decreased phosphorylation of protein kinase A/G sites as a mechanism.