Citations

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.

AbstractBackgroundWe assessed the long‐term clinical outcomes of an intermediate lesion (IL) according to the presence of a combined culprit lesion (CCL).HypothesisLong‐term clinical outcomes of IL may be affected by the presence of a CCL.MethodsAngiographic findings (n = 1096) and medical chart were reviewed. Patients with IL were divided into two groups: IL without CCL group (n = 383, 64.5%) and IL with CCL group (n = 211, 35.5%).ResultsThe major adverse cardiovascular events (MACE) in the IL with CCL group were significantly higher than those in the IL without CCL group (death: 12.3% vs. 7.0%, myocardial infarction: 3.3%vs. 0.5%, stroke: 6.6% vs. 2.6%, and revascularization [RVSC]: 25.1% vs. 7.6%) during a mean follow up period of 118.4 ± 5.5 months. IL related RVSC rate in the IL with CCL group was higher than that in the IL without CCL group (5.7% vs. 2.1%, p = 0.020). RVSC rate related to IL in total subjects was lower than that related to stented lesion (3.4% vs. 6.4%). The important predictors of total MACE in total subjects were the presence of CCL, IL percent diameter stenosis, hypertension, history of percutaneous coronary intervention, blood glucose and ejection fraction. The predictors of IL related RVSC were IL percent diameter stenosis and IL located in the right coronary artery.Conclusion10‐year clinical outcomes of an IL (especially IL without CCL) were better than those of stented lesions. This study suggests that the IL can be safely followed up in sites that do not have ability to assess functional study.

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.

Introduction: Patients with heart failure with preserved ejection fraction (HFpEF) may have elevated left ventricular filling pressure with exercise (LVFP-ex), despite normal LVFP at rest. We aimed to assess the diagnostic value of resting left atrial strain (LAS) in detecting elevated LVFP-ex in dyspneic patients evaluated by exercise stress echocardiography. Methods: We performed 2D-speckle tracking analysis for LAS in 669 consecutive patients (mean age 64 ± 14, men 53%) who underwent treadmill echocardiography evaluation and had LV ejection fraction ≥50%. Assessment of LVFP at rest was based on the 2016 ASE Guidelines for diastolic function assessment. We used the 2019 ESC HFA-PEEF diagnostic algorithm to define elevated LVFP-ex (early mitral inflow wave/septal early diastolic tissue velocity (E/e’) ≥ 15 after exercise) and calculate a continuous HFA-PEEF score. Results: LAS reservoir was lowest in patients with elevated LVFP at rest (n=81) and lower in those with normal resting FP who developed elevated LVFP-ex (n=108) compared to those who maintained normal LVFP-ex (29.0 ± 5.2% vs. 33.1 ± 5.0% vs.39.3 ± 4.8%, p < 0.001). In patients with normal or indeterminate LVFP at rest (n=587), LAS reservoir and pre-exercise HFA-PEEF score demonstrated an area-under-the-curve (AUC) of 0.82 and 0.7 respectively for elevated LVFP-ex. There was a 28% higher odds of developing elevated LVFP-ex per 1% decrease in LAS reservoir (odds ratio, 95%CI: 0.78, 0.74 - 0.82). In patients with the intermediate score (n=461), 123 patients developed elevation in LVFP with exercise and were classified as having HFpEF per the diagnostic algorithm. Addition of LAS reservoir improved the predictive value of HFA-PEEF score for HFpEF (AUC increased from 0.71 to 0.80, p for ΔAUC =0.01). Conclusions: LAS reservoir has a potential to identify patients at intermediate-risk for HFpEF who may develop elevated LVFP with exercise only, and therefore a promising parameter to aid in the diagnosis of HFpEF when exercise testing is not feasible.

Introduction: A low cardiac power output (CPO), measured invasively, identifies critically ill patients at increased risk of mortality. CPO can also be measured non-invasively with transthoracic echocardiography (TTE), although prognostic data in critically ill patients is not available. Hypothesis: Reduced CPO measured by TTE is associated with increased hospital mortality in cardiac intensive care unit (CICU) patients. Methods: Using a database of CICU patients admitted between 2007 and 2018, we identified patients with TTE within one day (before or after) of CICU admission who had data necessary for calculation of CPO. Multivariable logistic regression determined the relationship between CPO and adjusted hospital mortality. Results: We included 5,585 patients with a mean age of 68.3±14.8 years, including 36.7% females. Admission diagnoses included acute coronary syndrome (ACS) in 57%, heart failure (HF) in 50%, cardiac arrest (CA) in 12%, and cardiogenic shock (CS) in 13%. The mean left ventricular ejection fraction (LVEF) was 47±16%, and the mean CPO was 1.0±0.4 W. CPO was inversely associated with the risk of hospital mortality (Figure A), including among patients with ACS, HF, and CS (Figure B). On multivariable analysis, lower CPO was associated with higher hospital mortality (OR 0.96 per 0.1 W, 95% CI 0.0.93-0.99, p=0.03). Hospital mortality was highest in patients with low CPO coupled with reduced LVEF, increased vasopressor requirements, or higher admission lactate. Hospital mortality was higher among patients with a CPO <0.6 W (adjusted OR 1.57, 95% CI 1.13-2.19, p = 0.007), particularly in the presence of admission lactate level >4 mmol/L (50.9%). Conclusions: Echocardiographic CPO was inversely associated with hospital mortality in CICU patients, particularly among patients with increased lactate and vasopressor requirements. Routine measurement of CPO provides important information beyond LVEF and should be considered in CICU patients.

Objectives To evaluate outcomes of patients achieving a post‐treatment pathological stage of <ypT2N0 at radical cystectomy (RC) following neoadjuvant chemotherapy (NAC) for muscle‐invasive bladder cancer (MIBC) to identify an optimal definition of pathological response. Patients and Methods Patients from 10 international centres who underwent NAC for cT2–4aN0–1 MIBC and achieved <ypT2N0 disease at RC were included. The primary outcome was time to recurrence, either local or distant. Kaplan–Meier and Cox proportional hazards regression were used to evaluate associations between clinicopathological variables and outcomes. Results A total of 625 patients were included. The median age was 66 years and 80% were male. Gemcitabine and cisplatin (GC, 56%) and methotrexate, vinblastine, doxorubicin and cisplatin (MVAC)/dose‐dense (dd)MVAC (32%) were the most common NAC regimens. ypT0, pure ypTis, ypTa ±ypTis and ypT1 ± ypTis were attained in 58.1%, 20.0%, 7.6% and 14.2% of patients, respectively. The cumulative incidence of recurrence at 5 years was 9%, 16%, 29% and 30%, respectively. Pathological stage was prognostic for recurrence, with ypTa ± Tis (hazard ratio [HR] 3.20, 95% confidence interval [CI] 1.40–7.30) and ypT1 ± Tis disease (HR 4.03, 95% CI 2.13–7.63) associated with a significantly higher recurrence risk. Pure ypTis (HR 1.66, 95% CI 0.82–3.38) and the type of NAC regimen (ddMVAC: HR 1.59, 95% CI 0.55–4.56; MVAC: HR 1.18, 9%% CI 0.25–5.54; reference: GC) were not associated with recurrence. Conclusion We propose that optimal pathological response after NAC be defined as attainment of ypT0N0/ypTisN0 at RC. Patients with ypTaN0 or ypT1N0 disease (with or without Tis) at RC displayed a significantly higher risk of recurrence and may be candidates for trials investigating adjuvant therapy.