Oh, Jae K.

Background : Dyssynchrony indexes derived from time to peak systolic velocity and time to peak strain have been reported to predict left ventricular reverse remodeling (RR) after cardiac resynchronization therapy (CRT). The predictive characteristics of these indices have not been validated in a variety of clinical settings. Our objective was to determine the predictive value of strain and tissue velocity derived dyssynchrony indices for RR or clinical response to CRT in a prospective single-center CRT registry. Methods : Prospective registry of all heart failure patients (pts) undergoing CRT with echo before and 3 and 6 months after CRT. Color -coded tissue Doppler imaging in 12 segments was used to calculate the standard deviation of time to peak strain (Tϵ-SD) and time to peak systolic velocity (Tv-SD). RR was defined as a decrease in end systolic volume (ESV; biplane Simpson’s method) ≥15%. Indices were assessed with receiver-operating characteristics (ROC) analysis and the area under the curve (AUC) calculated in all pts and excluding those with atrial fibrillation at implant. Results : To date, of the first 87 patients, 4 died (classified as non-responder); 83 pts had 3 and 59 pts had 6 month echocardiography follow-up. Tϵ-SD (93%) and Tv-SD (98%) were feasible in most pts. RR occurred in 42 pts (51%) at 3 month and 32 patients (54%) at 6 month follow-up. See table . Tϵ-SD was superior to Tv-SD for prediction of RR in all pts and in those without atrial fibrillation. Findings were similar regardless of ischemic (68% of patients) or non-ischemic etiology. Neither baseline Tϵ-SD nor Tv-SD correlated with the improvement in clinical response measured by the change in six minute walk distance or peak VO 2 at 3 or 6 month after CRT (data not shown). Conclusions : In this single center experience, mechanical dyssynchrony measured by strain imaging but not tissue velocity imaging was predictive of RR. Neither index predicted clinical response.

Background: Effect of CRT on the timing of regional myocardial strain is not fully described. We aimed to explore the effect of CRT on the timing of regional myocardial strain using speckle tracking echocardiography (STE). Methods: STE and tissue Doppler imaging were performed in 91 patients before and 6 month after CRT. Time to peak longitudinal strain (Tϵ) from the onset of QRS was measured in 16 segments from three apical views. Time to peak systolic tissue velocity (Tv) was also measured in 12 basal and mid segments. Reverse remodeling was defined as 10% reduction in end-systolic volume. Results: At baseline, Tϵ and Tv demonstrated specific pattern with earlier septal and delayed lateral contraction (Figure ). Tϵ in responders showed significantly earlier timing in mid inferoseptal (p=0.003) and anteroseptal segments (base, P=0.005, mid P=0.007) than in nonresponders, whereas the timing of free wall did not differ between responders and non-responders. After CRT, Tϵ in earlier segments (inferoseptal, anteroseptal and inferior wall) prolonged significantly (p<0.001), whereas other segments did not change timing. Accordingly, SD of Tϵ in 12 segments reduced after CRT (110±46 ms vs. 81±36 ms, p<0.001). Tv did not change in all segments and SD of Tv did not improve after CRT (43±16 vs. 46±16 ms, p=0.20). Conclusions: Simultaneous electrical activation of LV free wall and septum with CRT achieves mechanical synchronization by delaying the timing of earlier contracting segment rather than directly shortening the timing in lateral wall. This could be explained by the increased wall stress on the septum as it contracts simultaneously with the opposing LV free wall. Figure. Change in Regional Timing in Strain and Peak Velocity

Background: Cardiac resynchronization therapy (CRT) improves global systolic function in left ventricle. However, the impact of CRT on regional myocardial function is less clear. The aim of this study, therefore, is to evaluate regional changes in myocardial strain after CRT. Methods: Speckle tracking echocardiography (STE) was performed in 91 patients before and 6 month after CRT. Peak longitudinal strain was measured in 18 segments at base, mid and apex in three apical views. Left ventricular end-systolic volume (ESV) was measured by biplane Simpson’s method and reverse remodeling was defined as 10 % reduction in ESV at 6 month after CRT. Results: Peak strain improved in basal and mid segments of medial walls (basal inferoseptal, anteroseptal and inferior segments, p<0.05, mid inferoseptal and inferior segments: p<0.01) in entire group after CRT, with a greater degree of improvement in CRT responders than in nonresponders (Figure ). There was no significant improvement in free wall strain, with significant reduction in basal inferolateral segment after CRT (P=0.047) in entire group. Nonresponders had significant reduction in strain at the mid anterolateral segment (P=0.004) (Figure ). Strain of the apical segments also did not improve. Conclusions: CRT induces reverse remodeling by enhancing regional myocardial function in the septum, but suppresses the function in the free wall. Lack of reverse remodeling after CRT was characterized by the reduced function in lateral segments without improvement in septal function..

Background: Radiation therapy (RT) to the chest may induce various combined cardiac problems such as constrictive pericarditis (CP), restrictive myocardial disease, and coronary artery disease. Therefore, it was hypothesized that the MRI and transthoracic echocardiographic (TTE) findings in patients with CP may differ according to the history of RT. Methods: A total of 68 patients with CP who performed both TTE and MRI study at Mayo Clinic from 2002 to 2008 were reviewed and divided into two groups according to the history of RT; RT group (group I, n=13, 53.6±9.8 years, 8 males) versus no RT group (group II, n=55, 59.0±14.8, 45 males). Results: The results of TTE study were summarized in table . Early diastolic velocity of septal mitral annulus (E′) and deceleration time (DT) of mitral inflow was significantly lower, and the ratio of early diastolic mitral inflow velocity (E) to E′ is significantly higher in group I than in group II. Left atrial volume index (LAVI) was significantly lower and LA area and left ventricular end-diastolic dimension (LVEDD) was significantly smaller in group I than in group II. Delayed enhancement of pericardium was the only significant finding in MRI and significantly prevalent in group I than in group II (100.0% in group I vs 63.6% in group II, p=0.012). The other MRI findings including pericardial thickness, left ventricular and right ventricular ejection fraction, and the presence of pericardial and pleural effusion were not different between the groups. Conclusion: In CP patients with the history of RT compared to patients without history of RT, E′ and DT was significantly lower, LAVI and LVEDD were smaller, pericardial DE in MRI was invariably found. The lower E′ velocity and decreased chamber size and volumes may be explained by RT induced coexisting myocardial disease. TTE findings of the patients

Objective: Recent MRI studies have demonstrated the common occurrence of late gadolinium enhancement (LGE) in cardiac amyloidosis (CA). However, the association of LGE presence and pattern with other clinical, morphological, functional, and biochemical parameters has not yet been demonstrated. It is important to define this association, since many of these parameters (NYHA class, ventricular thickness, cardiac biomarkers) have prognostic implications. Methods: Of 151 patients with confirmed systemic amyloidosis who underwent LGE cardiac MRI between January 2006 and December 2007 to evaluate for possible CA, 120 (AL 100, senile 9, and familial 11) were included after meeting of inclusion and exclusion criteria. Cine MRI images were analyzed for morphologic and functional data. LGE images were analyzed for presence and pattern of LGE. Clinical data including ECG’s and cardiac biomarkers was obtained. Results: LGE evidence of CA was present in 95 patients and absent in 25 patients. Three main patterns of LGE were observed. These were global diffuse transmural (homogenous or heterogenous) or subendocardial, suboptimally nulled myocardium without clear hyperenhancement, and focal patchy LGE. Symptoms, morphologic/functional variables, ECG voltages, and cardiac biomarker levels were worst in patients with global diffuse LGE, followed by suboptimally nulled myocardium, focal patchy LGE, and absent LGE groups (Table 1 ). Conclusions: The presence of LGE in amyloidosis patients is associated with worse clinical, morphologic, functional, and biochemical parameters. Amongst patients with abnormal LGE, global diffuse (transmural or subendocardial) LGE is associated with the worst profile. This provides initial evidence that the presence and pattern of LGE in CA is associated with other markers of prognosis.

Objective: In AL amyloidosis, early detection of cardiac involvement is desirable because of prognostic and therapeutic implications. Recent pilot MRI studies have demonstrated that late gadolinium enhancement (LGE) is a common finding in cardiac amyloidosis (CA) and reflects interstitial expansion due to amyloid infiltration. However it is not known whether evaluation of the myocardial substrate via LGE MRI may allow for earlier detection of CA compared with morphological assessment on the basis of increased left ventricular thickness (LVT). Methods: Between January 2006 and December 2007, 100 patients with confirmed AL amyloidosis underwent LGE MRI at our institution to evaluate for CA. Morphological evidence of CA was considered to be present when LVT was increased (mean of septum and inferolateral wall > 12 mm). LGE images were analyzed for presence and pattern of LGE. Clinical data was also reviewed. Results: Increased LVT was present in 69 patients. Abnormal LGE images were present in 76 patients (global diffuse transmural or subendocardial LGE in 43, suboptimally nulled myocardium in 18, and focal patchy LGE in 15 patients). LGE was present in 21 of 22 patients with a diagnosis of CA on cardiac biopsy. Seven patients (10%) with increased LVT did not have LGE. Conversely of 31 pts with normal LVT, 14 (45%) had abnormal LGE on MRI (usually suboptimally nulled myocardium or focal patchy LGE) and also had significantly higher incidence of low voltage ECG (50% vs. 0%), lower absolute limb lead voltage (6.5±3 vs. 9.7±2.6 mm), increased RV thickness (4.9±1.1 vs. 4.1±1) and higher BNP (316±376 vs. 107±103) compared to 17 patients without LGE (Table 1 ). Conclusions: MRI LGE is common in patients with CA and evaluation of the myocardial substrate using this technique may allow for earlier detection of cardiac involvement in AL amyloidosis compared with morphological assessment on the basis of increased LVT.

Background: Transcatheter aortic valve replacement (TAVR) is an alternative to surgical aortic valve replacement in patients at high surgical risk. We investigated the impact of TAVR on left (LV) and right ventricular (RV) function using conventional echocardiography parameters. Methods and results: A total of 202 consecutive patients (age 80.6±8.0 years, aortic valve area 0.80±0.16cm 2 ) who underwent TAVR at Mayo Clinic between 2008 and 2013 were included in the study. LV ejection fraction (EF) and RV systolic function including tricuspid annular plane systolic excursion (TAPSE), fractional area change (FAC) and, systolic excursion velocity (S’) were compared before (median 33.5 days) and after TAVR procedure (median 30 days). Patients who underwent pacemaker implantation after TAVR were excluded. LV EF significantly improved following TAVR (55.3±12.6% pre vs 58.5±11.1% post; p<0.05). In contrast, RV systolic function significantly decreased after TAVR (pre vs post; TAPSE: 18.8±6.3 mm vs 17.4±6.3 mm, FAC: 42.6±9.8% vs 37.3±8.2%; S’: 10.7±2.6 cm/s vs 10.2±2.6 cm/s; p<0.05 for all). Stratifying RV functional change by TAVR approach site, patients undergoing trans-femoral TAVR (n=100) showed RV deterioration only by FAC (see Table). In contrast, RV systolic dysfunction was more prominent in trans-apical approach group (n=87) with significant decline in all parameters of RV systolic function (see Table). Conclusion: TAVR is associated with early enhancement in LV systolic function. However, there is evidence of worsening RV function in a significant number of patients. Further studies are necessary to determine whether this deterioration in RV function is related to anatomic access site or to other factors, and to evaluate its prognostic significance.

Introduction: Whether echocardiographic (echo) markers of left ventricular (LV) remodeling and diastolic dysfunction contribute incremental and independent prognostic information to clinical risk markers in patients (Pts) with coronary artery disease and severe LV systolic dysfunction is unclear. We sought to determine which echo variables provide the greatest prognostic value in the Surgical Treatment for Ischemic Heart Failure (STICH) population. Methods: Pts enrolled in STICH for whom transmitral Doppler (E/A ratio) was available on a baseline echo interpreted by an echo core laboratory blinded to treatment and outcomes formed the analysis cohort. Comprehensive datasets to account for missing echo data were created by multiple imputation and the impact on all-cause mortality was determined with the Cox’s regression model. Results: E/A ratio could be measured in 1511 of the 2136 Pts enrolled in STICH. Amongst markers of diastolic dysfunction, E/A ratio was the most significant predictor of mortality (χ 2 41.05, p <0.001) with a non-linear, u-shaped, relationship. Mortality was lowest with E/A ratio = 1.0, and increased for E/A ratio <0.6 and >1.0 up to 2.3, beyond which there was no further increase in risk. The combination of larger LV end-systolic volume index (LVESVI), low or high E/A ratio, and mitral regurgitation severity grade, had highly significant incremental negative effects on mortality (χ 2 69.65, p<0.001) when added to a multivariable model with clinical risk markers. Overall, creatinine (χ 2 30.00, p <0.001), followed by LVESVI (χ 2 27.26, p<0.001), age, and E/A ratio (χ 2 12.46, p<0.001) were among the most significant predictors of mortality and accounted for 74% of the total prognostic information. LVESVI and E/A ratio were stronger predictors of poor prognosis than New York Heart Association (NYHA) functional class, hemoglobin, diabetes, stroke, or atrial fibrillation. Conclusions: Echo markers of advanced LV remodeling and diastolic dysfunction add incremental prognostic value to clinical risk markers and are more predictive of poor prognosis than advanced NYHA functional class or anemia. LVESVI and E/A ratio outperformed other echo markers and should be considered standard in assessing risk in Pts with ischemic LV dysfunction.

Introduction: Diastolic dysfunction impairs exercise capacity and has prognostic value in exercise echocardiography. We aimed to assess whether left atrial strain (LAS), which is reduced with worsening in diastolic function, is associated with all-cause death or heart failure hospitalization in patients undergoing treadmill echocardiography. Methods: We performed 2D-speckle tracking analysis of LAS in 1636 consecutive patients (mean age 64±13 and 59% men) who underwent treadmill echocardiography between 1/2013 and 1/2014. We used the 2016 ASE recommendation to define diastolic function and elevated LV filling pressure. Results: Of 1636 study subjects, 95% had LV ejection fraction ≥ 50%. Diastolic function was normal in 44% of patients and abnormal in the remaining (23% grade I, 9% grade II, 1% grade III, and 23% indeterminate). During a mean follow-up of 5.5±1.8 years, 210 patients (12.8%) experienced the composite outcome (157 death and 88 heart failure hospitalization). Lower LASreseroivr, LASbooster and LA emptying fraction (LAEF) were all associated with increased risk for the adverse outcome independent of age, sex, clinical and echocardiographic parameters, and after further adjustment for diastolic function (abnormal vs. normal) (all p≤0.001). The association of LASbooster with the outcome attenuated in a model with LASreservoir or LAEF (both p>0.1). Adding LASreservoir to clinical and echocardiographic parameters provided incremental prognostic value (continuous net reclassification improvement=0.09, p=0.04), but not LAEF or LASbooster. Patients with LASreservoir <34.2% (lowest tertile) had more than doubled risk for death or heart failure hospitalization than those with LASreservoir ≥34.2% after multivariable adjustment in the entire cohort (adjusted hazard ratio 2.2, 95%CI: 1.53 - 3.23), as well as in those with normal stress test (n=1217, adjusted HR, 3.53, 95%CI: 2.29 - 5.53) or those without elevated resting LV filling pressure (n=1466, adjusted HR: 2.08, 95%CI: 1.46 - 2.96). Conclusions: LASreservoir provides independent prognostic information in patients undergoing exercise echocardiography.