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Background: Recently, the left ventricular early inflow-outflow index (LVEIO), calculated by dividing mitral E-wave velocity by the left ventricular outflow velocity time integral, has been proposed as a simple method for evaluating mitral regurgitation (MR). This study determined the optimal LVEIO threshold to assess severe MR with different etiologies and assessed its prognostic value. Methods and Results: The records of 18,692 consecutive patients who underwent echocardiography were reviewed. MR was classified into 4 groups: Grade 0/1, no, trivial, or mild MR; Grade 2, moderate MR; Grade 3, moderate to severe MR; and Grade 4, severe MR. The mean (±SD) LVEIO of Grades 0/1, 2, 3, and 4 was 3.6±1.4, 6.0±2.5, 7.4±3.1, and 9.5±2.8, respectively. An optimal LVEIO threshold of 5.4 was determined to distinguish moderate to severe or severe MR from non-severe MR (sensitivity 84%, specificity 91%). Kaplan-Meier survival analysis revealed high mortality in the group with LVEIO ≥5.4 (P=0.009, hazard ratio 1.833). This was found only in primary MR when separate analyses were performed according to etiology. Multivariate analysis revealed that LVEIO was an independent predictor for all-cause death only in primary MR. Conclusions: Using appropriate thresholds, LVEIO is a simple and useful method to diagnose severe MR regardless of etiology. LVEIO can also be useful for predicting prognosis in primary MR.

BACKGROUND We used dual Doppler echocardiography to measure the time interval between the mitral and tricuspid valve opening (MO-TO time), which we expected would reflect the balance between left and right ventricular hemodynamics. Methods and Results: We prospectively enrolled 60 patients with heart failure (HF) and sinus rhythm. The MO-TO time was measured in addition to routine echocardiography parameters, invasive hemodynamic parameters and plasma B-type natriuretic peptide (BNP) level in all patients. Patients were divided into 2 groups based on the MO-TO time: MOP (mitral opening preceding tricuspid opening), and TOP (tricuspid opening preceding mitral opening) groups. We followed up the predefined adverse outcomes (cardiovascular [CV] death and hospitalization due to worsening HF) for 1 year. Pulmonary artery wedge pressure (PAWP) and mean pulmonary artery pressure (mPAP) were higher in the MOP than in the TOP group (P

Introduction: Myofibril deposition in amyloidosis diffusely may affect cardiac structure and function. Right ventricular involvement has been associated with adverse clinical outcome. However, the utility of right atrial (RA) function assessment by echocardiographic strain imaging is unclear. Hypothesis: We hypothesize that right atrial stain has prognostic value in cardiac amyloidosis. Methods: We studied 121 consecutive patients with cardiac amyloidosis: 18% had transthyretin and 79% had light chain amyloidosis. Cardiac amyloidosis was either confirmed by endocardial biopsy (36%) or by a combination of non-cardiac tissue biopsy and proof of left ventricular hypertrophy (64%). Speckle tracking peak RA reservoir strain was assessed based on 6 segments from the apical 4-chamber view. All-cause mortality was tracked over a median of 5 years. Results: Echocardiographic peak longitudinal RA strain was feasible in 109 patients (90%). 60 CA patients died during follow-up period. Peak longitudinal RA strain was reduced in cardiac amyloidosis non-survivors (8.1%) in comparison to survivors (18.3%, p Conclusions: Reduced peak longitudinal RA strain was significantly associated with survival in patients with cardiac amyloidosis. RA reservoir function assessed by strain appears to be useful as a new means to predict prognosis in cardiac amyloidosis patients and has promise for clinical application.

Introduction: Light chain cardiac amyloidosis (AL) has a variable but usually poor prognosis. Left ventricular (LV) function measures including LV strain imaging for global longitudinal strain (GLS) have shown clinically prognostic value in AL. However, the utility of novel left atrial (LA) strain imaging and its associations with LV disease remains unclear. Hypothesis: LA strain is of additive prognostic value to GLS in AL. Methods: We included 99 consecutive patients with AL. Cardiac amyloidosis either confirmed by endocardial biopsy (25%) or by non-cardiac tissue biopsy and imaging data supportive of cardiac amyloidosis. Peak LA reservoir strain was calculated as an average of peak longitudinal strain from apical 2- and 4-chamber views. GLS and apical sparing ratio were assessed using the 3 standard apical views. All-cause mortality was tracked over a median of 5 years. Results: Echocardiographic GLS and peak longitudinal LA strain were feasible in 96 (97%) and 86 (87%) of patients, respectively. There were 48 AL patients who died during follow-up. Patients with low GLS (GLS < median; 10.3% absolute values) had worse prognosis than patients with high GLS group (p Conclusions: Peak longitudinal LA strain was additive to LV GLS in predicting prognosis in patients with biopsy confirmed AL amyloidosis. LA strain imaging has potential clinical utility in patients with AL cardiac amyloidosis.

Introduction: Little is known about global and segmental atrial function in cardiac amyloidosis. Atrial function plays an important role to maintain adequate ventricular filling. Hypothesis: We hypothesized left atrial (LA) and right atrial (RA) segmental strain analysis is prognostic in patients with cardiac amyloidosis. Methods: We studied 121 patients with biopsy-proven cardiac amyloidosis and speckle-tracking strain echocardiography. The LA and RA were divided into 6 segments each (basal, mid, and apical segments of free wall and septum). We determined LA and RA free wall/septal wall peak strain ratios. The primary outcome was all-cause mortality (median follow-up; 5.0 years). Results: Regional LA strain analysis was feasible in 104 patients (86%) and RA in 92 patients (76%). Average LA global peak strain was 18.3±12.1% and RA global peak strain was 20.0±15.0%. We compared LA and RA strain free wall and septal wall segments. Atrial septal strain was significantly reduced compared to free wall strain in RA (10.8±9.9 % vs 30.7± 23.8%, p< 0.01). Free wall/septal wall strain ratio of LA was significantly reduced compared with the ratio of RA (p< 0.01). During the follow up, 60 patients died. All atrial regions showed reduction in peak strain in non-survivors compared with survivors. When dividing patients into 2 groups using LA free wall strain and RA free wall strain median values, low atrial free wall strain was associated with worse prognosis (Log-rank p < 0.001, HR 4.9, 95% CI= 2.6-9.3). Conclusions: LA and RA atrial strain have significant prognostic value in patients with cardiac amyloidosis. Free wall/septal wall strain ratio in LA was significantly reduced compared with RA. Assessment of atrial dysfunction has promise for clinical applications cardiac amyloidosis patients.

Introduction: Guidelines favor patient selection by left bundle branch block (LBBB) with QRS width ≥150 ms for cardiac resynchronization therapy (CRT). Predicting CRT response in patients with QRS width 120 to 149 ms or non-LBBB remains difficult. Left ventricular (LV) global longitudinal strain (GLS) and systolic stretch index (SSI) have shown to characterize the ventricular substrate responsive to CRT. However, the potential application of longitudinal left atrial (LA) strain remains unclear. Hypothesis: Baseline LA strain has prognostic value in CRT patients with intermediate ECG criteria. Methods: We studied 195 patients who underwent CRT based on routine indications: ejection fraction ≤35% and QRS width ≥120 ms. GLS was assessed using the 3 standard apical views. Radial SSI was derived from the mid LV short axis view. Peak longitudinal LA strain was derived from the 2 and 4-chamber apical view. The predefined combined clinical endpoint was death, heart transplant or left ventricular assist device over 4 years after CRT. Results: LA strain was feasible in 162 (83%) of the CRT candidates: QRS duration 156 ± 26 ms, 39.5% had LBBB with QRS ≥ 150ms, 60.5% had intermediate ECG criteria. High peak longitudinal strain (>median, 10.1%) was associated with favorable event-free survival (pmedian, 8.4%) had similar outcome to those with Class I indications for CRT. Multivariable analysis revealed that LA strain had independent prognostic value (hazard ratio 0.9 per LA strain %, p < 0.001) even after adjusted for other clinical, electrophysiological and echocardiographic covariates including QRS morphology and duration, GLS and SSI. Conclusions: Peak LA strain had important prognostic value in candidates for CRT. Prognostic value of LA strain was additive to LV strain characteristics and most significant in CRT patients with intermediate ECG criteria for CRT.

The prognostic value of echocardiographic atrial and ventricular strain imaging in patients with biopsy-proven cardiac amyloidosis was assessed.Although left ventricular global longitudinal strain (GLS) is known to be predictive of outcome, the additive prognostic value of left (LA), right atrial (RA), and right ventricular (RV) strain is unclear.One hundred thirty-six patients with cardiac amyloidosis and available follow-up data were studied by endomyocardial biopsy, noncardiac biopsy with supportive cardiac imaging, or autopsy confirmation. One hundred nine patients (80%) had light-chain, 23 (17%) had transthyretin, and 4 (3%) had amyloid A type cardiac amyloidosis. GLS, RV free wall strain, peak longitudinal LA strain, and peak longitudinal RA strain were measured from apical views. Clinical and routine echocardiographic data were compared. All-cause mortality was followed (median 5 years).Strain data were feasible for GLS in 127 (93%), LA strain in 119 (88%), RA strain in 117 (86%), and RV strain in 102 (75%). Strain values from all 4 chambers were significantly associated with survival. Hazard ratio (HR) and 95% confidence interval (CI) for low median strain values were as follows: GLS, HR: 2.3; 95% CI: 1.3 to 3.8 (p 0.01); LA strain, HR: 7.5; 95% CI: 3.8 to 14.7 (p 0.001); RA strain, HR: 3.5; 95% CI: 2.0 to 6.2 (p 0.001); and RV free wall strain, HR: 2.8; 95% CI: 1.5 to 5.1 (p 0.001). Peak longitudinal LA strain and RV strain remained independently associated with survival in multivariable analysis. Peak LA strain had the strongest association with survival (p 0.001), and LA strain combined with GLS and RV free wall strain had the highest prognostic value (p 0.001).Strain data from all 4 chambers had important prognostic associations with survival in patients with biopsy-confirmed cardiac amyloidosis. Peak longitudinal LA strain was particularly associated with prognosis. Atrial and ventricular strain have promise for clinical utility.

Background Guidelines favor patient selection by left bundle branch block (LBBB) with QRS width ≥150 ms for cardiac resynchronization therapy (CRT). However, predicting response to CRT patients with QRS width 120 to 149 ms or non-LBBB remains difficult. Speckle tracking left atrial (LA) strain is a novel means to assess cardiac function, however its applications to CRT patients remains unclear. Purpose To test the hypothesis that baseline LA strain has prognostic value in CRT patients with intermediate ECG criteria. Methods We studied 195 patients with heart failure (HF) who underwent CRT based on routine indications: ejection fraction ≤35% and QRS width ≥120 ms. GLS was assessed using the 3 standard apical views. LA longitudinal strain was based on 12 segments from the 2 and 4-chamber apical view. Peak LA strain, a measure associated with the reservoir function of the LA, was defined as the average of peak longitudinal strain from all segments. The predefined combined clinical endpoint was death, heart transplant or left ventricular assist device (LVAD) over 4 years after CRT. Results LA strain was feasible in 162 (83%) of the candidates for CRT: age 64±11 years, 72% male, QRS duration 156±26 ms, 39.5% had LBBB with QRS ≥150ms, 60.5% had intermediate ECG criteria. Median LA strain was 11.0% [1.3% - 36.8%]. High LA peak strain was associated with more favorable event-free survival and Low LA Peak strain was associated with worse clinical outcome following CRT (FIGURE, p Conclusions Baseline peak LA strain had important prognostic value in HF patients who are candidates for CRT. Prognostic value of LA strain was most significant in CRT patients with intermediate ECG criteria (QRS 120 to 149ms or non-LBBB) and has promise for clinical applications. LA strain and clinical outcome after CRT Funding Acknowledgement Type of funding source: None

Balloon aortic valvuloplasty (BAV) is used in high-risk patients with severe aortic stenosis (AS) when the benefit of transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR) is unclear. Our objective was to identify clinical or echocardiographic features that identify patients likely to benefit from BAV.We studied 141 consecutive patients who underwent BAV from July, 2011 to October, 2017. Clinical characteristics, routine echocardiographic parameters, and speckle tracking imaging of global longitudinal strain (GLS) were assessed before and after BAV. The primary outcome was all-cause mortality as ascertained by the National Death Index.There were 141 patients, median age, 80 years (interquartile range [IQR], 74-87 years) with severe AS (median aortic valve area, 0.66 cm²; IQR, 0.53-0.79 cm²) and median mean gradient of 36 mm Hg (IQR, 27-48 mm Hg) who underwent BAV. The 1-year mortality rate was 52%. Characteristics associated with survival were New York Heart Association class I symptoms, lower brain natriuretic peptide level, higher left ventricular ejection fraction (LVEF)53%, and higher GLS (13.2%; absolute values were used for GLS). Landmark analysis at 60 days showed the 47 patients who underwent TAVR/SAVR after BAV had significantly better 1-year survival than those who did not (P.001).A high 1-year mortality rate was observed in severe AS patients selected for BAV. LVEF and left ventricular (LV)-GLS offer similar prognostic value for 1-year mortality; however, LV-GLS may have potentially increased clinical utility, as it provides a clear threshold for predicting poor outcomes compared with LVEF. As patients who undergo TAVR/SAVR have markedly improved mortality, careful consideration should be given to advance definitive valve therapy in carefully selected BAV patients.

Background Apical sparing by longitudinal strain imaging has reported utility for the diagnosis of cardiac amyloidosis. However, potential differences in the apical sparing pattern in light chain (AL) versus transthyretin (ATTR) amyloidosis in patients with high clinical suspicion for cardiac amyloidosis is not clear. Purpose Our objective was to test the hypothesis that echocardiographic strain imaging could determine differences in patients with clinically suspected AL and ATTR cardiac amyloidosis. Methods We studied 206 patients, aged 64±11, with clinically suspected cardiac amyloidosis. Routine longitudinal strain imaging analyses was performed (EchoPAC, GE Healthcare) with bulls-eye plots. After 27 exclusions (8 arrhythmia/frame rate, 19 missing/poor images), there were 179 patients. Included were 129 patients with cardiac amyloid: 42 by endomyocardial biopsy, 4 by technetium pyrophosphate scan, 65 by non-cardiac biopsy with suggestive cardiac imaging (interventricular septal thickness ≥1.2cm by echocardiography or characteristic cardiac MRI findings), 15 with multiple myeloma and suggestive cardiac imaging, and 3 by autopsy; 50 patients had a negative endomyocardial biopsy or autopsy for cardiac amyloid. The apical sparing ratio by strain imaging was calculated as the (average of apical segments) / (average of mid segments + average of basal segments). Results Cardiac amyloidosis patients were 79% with AL and 21% with ATTR. Applying the previously published apical sparing ratio cut-off of 1.0 for longitudinal strain imaging, sensitivity and specificity were 29% and 78%, respectively, for diagnosis of cardiac amyloidosis. Applying a ratio cut-off of 0.81 improved sensitivity to 72% with specificity of 64% and area under the curve (AUC) of 0.66. Positive and negative predictive values were 85% and 46%, respectively, at this ratio cut-off. The apical sparing ratio was significantly higher in AL and ATTR as compared to the biopsy negative group (p Apical sparing pattern and ratio Conclusions Among patients with high clinical suspicion for cardiac amyloidosis, the apical sparing ratio by echocardiographic strain imaging can demonstrate differences for AL and ATTR cardiac amyloidosis and has potential for clinical utility.

Balloon aortic valvuloplasty (BAV) is used as a “bridge to decision” in patients deemed prohibitive risk for surgery or when the benefit of transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR) are unclear. This study evaluated if global longitudinal strain (

Right ventricular (RV) dysfunction is a predictor of heart failure patient outcomes. The prognostic utility of RV dysfunction by routine echo measures and strain imaging in cardiac amyloidosis is unclear. We studied 120 patients with cardiac amyloidosis identified by cardiac biopsy, autopsy, Tc-99m

Apical sparing of longitudinal strain has diagnostic utility for cardiac amyloidosis. However, the prognostic value of this finding in cardiac amyloidosis is uncertain. We included 136 patients diagnosed with cardiac amyloidosis with echocardiograms performed at the time of diagnosis. Speckle

Background Iron is associated with the pathophysiology of several cardiovascular diseases, including pulmonary hypertension (PH). In addition, disrupted pulmonary iron homeostasis has been reported in several chronic lung diseases. Transferrin receptor 1 (TfR1) plays a key role in cellular iron transport. However, the role of TfR1 in the pathophysiology of PH has not been well characterized. In this study, we investigate the role of TfR1 in the development of hypoxia-induced pulmonary vascular remodeling. Methods PH was induced by exposing wild-type (WT) mice and TfR1 hetero knockout mice to hypoxia for 4 weeks and evaluated via assessment of pulmonary vascular remodeling, right ventricular (RV) systolic pressure, and RV hypertrophy. In addition, we assessed the functional role of TfR1 in pulmonary artery smooth muscle cells in vitro. Results The morphology of pulmonary arteries did not differ between WT mice and TfR1 hetero knockout mice under normoxic conditions. In contrast, TfR1 hetero knockout mice exposed to 4 weeks hypoxia showed attenuated pulmonary vascular remodeling, RV systolic pressure, and RV hypertrophy compared with WT mice. In addition, the depletion of TfR1 by RNA interference attenuated human pulmonary artery smooth muscle cells proliferation induced by platelet-derived growth factor-BB (PDGF-BB) in vitro. Conclusions These results suggest that TfR1 plays an important role in the development of hypoxia-induced pulmonary vascular remodeling.

Background: Little evidence exists on the effects of exercise guidance in patients with acute aortic dissection after a period of complete bed rest. Few studies have examined changes in skeletal muscle during such periods in patients with cardiovascular disease. This retrospective study sought to investigate changes in skeletal muscle in the standard rehabilitation period in patients with aortic dissection and to discuss an optimal rehabilitation approach to promote safe early return to the community. Methods: Subjects were 54 patients with conservatively treated acute aortic dissection in whom serial computed tomography (CT) was performed for assessment of complications and follow-up observation of the aortic dissection. Using CT images, cross-sectional areas of the erector spinae muscle at the 7th cervical (A) and 3rd lumber vertebrae (B), the rectus abdominis muscle at the umbilical level (C), and the psoas major muscle at the 5th lumbar vertebra (D), were compared at different time points. Results: All patients were hypertensive, with the proportion of untreated patients being higher than that of treated patients. Cross-sectional areas of (A) and (B) significantly decreased approximately one week after admission compared with those at admission (p=0.0001). Cross-sectional area of (D) significantly decreased approximately one month after admission (near discharge) (p=0.0002). The decrease in the cross-sectional area of these muscles persisted up to two months after admission (p=0.0002). There were no changes over time with (C). Conclusion: Muscle weakness not only leads to reduced activities of daily living but also adverse events such as a fall. Development of a rehabilitation program involving resistance training is needed to promote early return to the community, although control of blood pressure is a prerequisite.

Right ventricular (RV) dysfunction assessed by RV strain imaging is a new marker for prognosis in patients with pulmonary hypertension (PH). The objective was to test the hypothesis that right atrial (RA) strain has additive prognostic value. We studied 153 patients with pre-capillary PH, aged 55±

Vector flow mapping (VFM) can quantify left ventricular (LV) flow mechanics noninvasively. VFM can measure LV energy loss and pump efficiency. However, the association of LV energy loss to symptom severity and serum biomarkers in heart failure patients with reduced ejection fraction (HFrEF) is

Vector Flow mapping (VFM) enables noninvasive quantification of cardiac flow dynamics. The impact of diastolic dysfunction on energy loss by VFM in heart failure (HF) patients is unclear. Our aim was to assess the association of VFM diastolic energy loss with conventional measures of diastolic

Lung transplantation is important therapeutic option for scleroderma patients with end stage lung disease. The means to determine long term prognosis after transplantation remains unclear. We studied 59 scleroderma patients before lung transplantation with routine and speckle tracking echo. A

Subarachnoid hemorrhage (SAH) can be associated with an acute stress cardiac injury. A reverse takotsubo pattern with apical sparing has been described, but not clearly understood. From our prospective study (R01NR04221), 221 patients with acute aneurysmal SAH had a strain echo on 2.3 days from

Left atrial (LA) function is important in heart failure. LA strain is a novel method to quantify LA function. We hypothesized that LA strain has prognostic significance in peripartum cardiomyopathy (PPCM). We studied 100 PPCM patients in the multicenter Pregnancy Associated Cardiomyopathy study [LV

Background: Diastolic dysfunction determines symptoms and prognosis in patients with left ventricular (LV) dysfunction. Diastolic wall strain (DWS) is associated with poor outcomes in heart failure with preserved ejection fraction. However, the utility of DWS is still unknown in heart failure with reduced ejection fraction (HFrEF). Our aim is to determine whether DWS is predictive of the outcome in HFrEF. Methods: We studied 54 HFrEF patients (LVEF Results: DWS increased after the induction of beta-blockade (0.32±0.11 vs 0.25±0.12,pmedian during 7 years (Log-rank p =0.025). DcT, EF, E’, HR at rest and log BNP before the induction of beta blockade were not significant predictors of HF outcome (Log-rank p=0.263, 0.504, 0.0796, 0.289 and 0.877) respectively. Conclusions: Induction of beta-blockade provided an improvement in DWS. DWS might be useful as an index of myocardial stiffness to predict the outcomes in HFrEF patients with chronic beta-blockade therapy.

There are some difficulties and limitations for the quantification of mitral regurgitation (MR) severity and integrated approaches using echocardiography are recommended. Recently, left ventricular early inflow-outflow index (LVEIO index), which is calculated by dividing the mitral E-wave velocity