Longitudinal strain by speckle tracking and echocardiographic parameters as predictors of adverse cardiovascular outcomes in chronic Chagas cardiomyopathy

To analyze the prognostic value of left ventricular global longitudinal strain (LV-GLS) and other echocardiographic parameters to predict adverse outcomes in chronic Chagas cardiomyopathy (CCM). Prospective cohort study conducted in 177 consecutive patients with different CCM stages. Transthoracic echocardiography measurements were obtained following the American Society of Echocardiography recommendations. By speckle-tracking echocardiography, LV-GLS was obtained from the apical three-chamber, apical two-chamber, and apical four-chamber views. The primary composite outcome (CO) was all-cause mortality, cardiac transplantation, and a left ventricular assist device implantation. After a median follow-up of 42.3 months (Q1 = 38.6; Q3 = 52.1), the CO incidence was 22.6% (95% CI 16.7–29.5%, n = 40). The median LV-GLS value was − 13.6% (Q1 = − 18.6%; Q3 = − 8.5%). LVEF, LV-GLS, and E/e′ ratio with cut-off points of 40%, − 9, and 8.1, respectively, were the best independent CO predictors. We combined these three echocardiographic markers and evaluated the risk of CO according to the number of altered parameters, finding a significant increase in the risk across the groups. While in the group of patients in which all these three parameters were normal, only 3.2% had the CO; those with all three abnormal parameters had an incidence of 60%. We observed a potential incremental prognostic value of LV-GLS in the multivariate model of LVEF and E/e′ ratio, as the AUC increased slightly from 0.76 to 0.79, nevertheless, this difference was not statistically significant (p = 0.066). LV-GLS is an important predictor of adverse cardiovascular events in CCM, providing a potential incremental prognostic value to LVEF and E/e′ ratio when analyzed using optimal cut-off points, highlighting the potential utility of multimodal echocardiographic tools for predicting adverse outcomes in CCM.

Prognostic Value of T1 Mapping and Feature Tracking by Cardiac Magnetic Resonance in Patients With Signs and Symptoms Suspecting Heart Failure and No Clinical Evidence of Coronary Artery Disease

Background The ability of left ventricular ejection fraction (LVEF) and late gadolinium enhancement (LGE) by cardiac magnetic resonance for risk stratification in suspected heart failure is limited. We aimed to evaluate the incremental prognostic value of cardiac magnetic resonance‐assessed extracellular volume fraction (ECV) and global longitudinal strain (GLS) in patients with signs and symptoms suspecting heart failure and no clinical evidence of coronary artery disease. Methods and Results A total of 474 consecutive patients (57±21 years of age, 56% men) with heart failure‐related symptoms and absence of coronary artery disease underwent cardiac magnetic resonance. After median follow‐up of 18 months, 59 (12%) experienced the outcome of all‐cause death or heart failure hospitalization (DeathCHF). In univariate analysis, cardiac magnetic resonance‐assessed LVEF, LGE, GLS, and ECV were all significantly associated with DeathCHF. Adjusted for a multivariable baseline model including age, sex, LVEF and LGE, ECV, and GLS separately maintained a significant association with DeathCHF (ECV, hazard ratio [HR], 1.44 per 1 SD increase; 95% CI 1.13–1.84; P =0.003, and GLS, HR, 1.78 per 1 SD increase; 95% CI, 1.06–2.96; P =0.028 respectively). Adding both GLS and ECV to the baseline model significantly improved model discrimination (C statistic from 0.749 to 0.782, P =0.017) and risk reclassification (integrated discrimination improvement 0.046 [0.015–0.076], P =0.003; continuous net reclassification improvement 0.378 [0.065–0.752], P <0.001) for DeathCHF, beyond LVEF and LGE. Conclusions In patients with signs and symptoms suspecting heart failure and no clinical evidence of coronary artery disease, joint assessment of GLS and ECV provides incremental prognostic value for DeathCHF, independent of LVEF and LGE.

Prognostic value of left atrial function in patients with severe primary mitral regurgitation undergoing mitral valve repair

Background Timing of mitral valve surgery for primary mitral regurgitation (MR) remains challenging. Since MR has a significant hemodynamic impact on the left atrium (LA), assessment of LA function may have prognostic value in these patients which is incremental to LA volume and left ventricular (LV) remodeling parameters. Purpose This study sought to investigate whether preoperative assessment of LA reservoir strain (LASr) by speckle tracking echocardiography is associated with long-term outcome in patients undergoing mitral valve repair for severe primary MR. Methods Echocardiography was performed prior to mitral valve surgery in 566 patients (age 64±12 years, 66% men) with severe primary MR. Complete clinical information was collected and the endpoint was all-cause mortality after operation. The study population was divided based on a cut-off value of LASr (22%) derived from a spline curve analysis (hazard ratio for all-cause mortality &gt;1). Results Patients with LASr ≤22% (n=277) were significantly older, had more impaired renal function and were more symptomatic (NYHA functional class III to IV) compared to patients with LASr &gt;22% (n=289). In terms of echocardiographic data, patients with LASr ≤22% had significantly lower LV ejection fraction and LV global longitudinal strain (LV-GLS) and significantly higher systolic pulmonary artery pressures and LA volume index compared with patients with LASr &gt;22%. During a median follow-up of 95 (56 – 147) months, 129 patients (22.8%) died. Patients with LASr ≤22% experienced significantly higher mortality rates compared to patients with LASr &gt;22% (log rank chi-square 35.1; p&lt;0.001) (Figure). On multivariable analysis, age (hazard ratio (HR): 1.06; 95% confidence interval (CI): 1.03 to 1.09; p&lt;0.001), LV-GLS (HR: 1.08; 95% CI: 1.02 to 1.15; p=0.014) and LASr (HR: 0.96; 95% CI: 0.93 to 0.99; p=0.014) were independently associated with all-cause mortality. The addition of LASr to a clinical model (including: age, coronary artery disease, estimated glomerular filtration rate, NYHA class III-IV, atrial fibrillation, LV end-diastolic volume index, LV ejection fraction, LV-GLS, LA volume index and systolic pulmonary artery pressure) showed a significant increase in the chi-square value (chi-square differences = 6.9; p=0.011), demonstrating the incremental prognostic value of LASr in patients with primary MR. Conclusions Preoperative LASr is independently associated with all-cause mortality in patients undergoing mitral valve repair for primary MR, has incremental prognostic value over LA volume and LVEF and might therefore be helpful to guide surgical timing. FUNDunding Acknowledgement Type of funding sources: Other. Main funding source(s): Jan Stassen has received an ESC training grant (Appehab724.011364741) Association of LASr and outcome

RV free wall longitudinal strain as an independent predictor of survival in wtATTR-CA patients

Background Wild type transthyretin cardiac amyloidosis (wtATTR-CA) is increasingly recognized as a cause of heart failure with preserved ejection fraction (HFpEF) but prognosis is often limited due to late or misdiagnosis.Longitudinal left ventricular strain and biomarkers are established as markers of disease severity, but the role of RV free wall strain, reflecting RV contractility, is less well understood. Purpose We sought to determine whether RV free wall strain might add incremental prognostic value in wtATTR-CA. Methods Consecutive patients diagnosed with wtATTR-CA with tissue confirmation at Mayo clinic between 2013 and 2015 were included. Patients with TTR gene mutations were excluded. Baseline characteristics and transthoracic echocardiography measurements were obtained from the medical records. Speckle tracking RV free wall longitudinal 2D strain and peak LA longitudinal 2D strain were measured using Tom Tec Imaging System. Survival was determined using Kaplan Meier estimates and using the cox proportional hazard ratio, univariate and multivariable analysis were performed to identify predictors of mortality in patients with wtATTR. Results The study group comprised 139 patients (mean age 74.9±8.6, 92.8% male), of which 102 had adequate image quality for RV strain, and 99 for LA strain. Amongst these, 102 (73.3%) had AF and 118 patients (84.8%) had HF. During 3.23±2.0 years of follow up, 66 patients died. Both mean RV and LA strain were impaired at baseline: RV free wall strain was −14.7±4.9, and peak atrial longitudinal strain (PALS) was 13.2±8.8%. Using ROC analysis, RV strain of −16.8% was an independent predictor of all-cause mortality. In univariate modeling, higher levels of NT-proBNP (HR: 1.1 per 1000 pg.ml; 95%, CI 1.05–1.15, p&lt;0.001) and Troponin T (HR: 2.0 per 0.1ng/ml; 95% CI 1.49–2.61, p&lt;0.001) were associated with increased all-cause mortality. In addition, LV GLS (HR: 1.13 per 1%; 95% CI1.04–1.24, p=0.003), RV free wall LS (HR: 2.16 per 5%; 95%, CI 1.57–3.03, p&lt;0.0001), and PALS (HR: 0.91 per1%; 95% CI 0.85–0.96, p&lt;0.0001) were univariate predictors of all-cause mortality. In multivariate analysis using a stepwise regression model, RV free wall longitudinal strain (HR: 1.81; 95% CI 1.29–2.62, p&lt;0.001) and Troponin T (HR: 1.7; 95% CI 1.25–2.26, p=0.001) remained independent predictors. Kaplan-Meier survival analysis demonstrated a higher mortality rate above −16.8 RV strain cut-off (Wilcoxon &lt;0.0001). All stages were divided into two groups by −16.8% RV strain, and survival in individual stages analyzed. Stage 1 and 2 with &lt;−16.8 RV free wall strain value had higher mortality than ≤-16.8% RV strain (Stage 1: Wilcoxon = 0.0041 and Stage 2: Wilcoxon = 0.023). However, there was not a survival difference between two RV strain groups in stage3 (Wilcoxon = 0.34) Conclusion RV free wall strain is an independent predictor of survival in wtATTR patients and may add incremental prognostic value to NT-proBNP and Troponin. FUNDunding Acknowledgement Type of funding sources: None. Kaplan-Meier curve of all patients Kaplan-Meier curve of stages

Mortality among patients undergoing dipyridamole 99mTc Sestamibi SPECT: impact of blunted heart rate response and abnormal scans

Background Blunted heart rate response (BHRR) caused by cardiac neuropathy associated with dipyridamole stress, has been linked to cardiovascular (CV) outcome events. Whether BHRR is necessarily associated with abnormal perfusion is unknown. The aim of the study was to assess the incremental prognostic value of BHRR in a single center population undergoing Dipyridamole 99mTc Sestamibi SPECT test (DSPECT) for predicting late CV events. Methods 388 patients (aged 73±10 years, 45% females, 51% with known coronary disease) that underwent DSPECT over 3 years period were included. Abnormal DSPECT and BHRR were evaluated in relation to late death. Results Mean follow up period was 1560±565 (15–2431) days. During follow up period, 90 patients died. Mode of death was CV in 20 and non-CV in 70. BHRR (&lt;20% heart rate increase), abnormal DSPECT, post-stress LVEF &lt;60% and reversible defects were observed in 63%, 41%, 23% and 20% of patients, respectively. BHRR (HR -2.41, p&lt;0.0006) and abnormal DSPECT (HR-1.62, p=0.02) were predictors of all-cause death. BHRR had incremental prognostic value over abnormal DSPECT (Figure, p&lt;0.0005). Multivariable analysis identified age, dyspnea, insulin treated diabetes mellitus and dialysis as independent predictors of death while DSPECT and BHRR did not. However, BHRR remained a significant predictor of CV death [HR 8.1 (1.06, 62.0), p&lt;0.05]. Conclusions In this contemporary DSPECT cohort, BHRR and DSPECT failed to predict all-cause mortality. However, BHRR was an independent predictor of CV death. FUNDunding Acknowledgement Type of funding sources: None. BHRR stratifies abnormal DSPECT

Left Atrioventricular Coupling Index to Predict Incident Heart Failure: The Multi-Ethnic Study of Atherosclerosis

Background: Although left atrial (LA) and left ventricular (LV) structural and functional parameters have independent prognostic value as predictors of heart failure (HF), the close physiological relationship between the LA and LV suggest that the assessment of LA/LV coupling could better reflect left atrioventricular dysfunction and be a better predictor of HF.Aim: We investigated the prognostic value of a left atrioventricular coupling index (LACI), measured by cardiovascular magnetic resonance (CMR), as well as change in LACI to predict incident HF in the Multi-Ethnic Study of Atherosclerosis (MESA).Materials and Methods: In the MESA, 2,250 study participants, free of clinically recognized HF and cardiovascular disease (CVD) at baseline, had LACI assessed by CMR imaging at baseline (Exam 1, 2000–2002), and 10 years later (Exam 5, 2010–2012). Left atrioventricular coupling index was defined as the ratio of LA to LV end-diastolic volumes. Univariable and multivariable Cox proportional hazard models were used to evaluate the associations of LACI and average annualized change in LACI (ΔLACI) with incident HF after adjustment for traditional MESA-HF risk factors. The incremental risk prediction was calculated using C-statistic, categorical net reclassification index (NRI) and integrative discrimination index (IDI).Results: Among the 2,250 participants (mean age 59.3 ± 9.3 years and 47.6% male participants), 50 incident HF events occurred over 6.8 ± 1.3 years after the second CMR exam. After adjustment, greater LACI and ΔLACI were independently associated with HF (adjusted HR 1.44, 95% CI [1.25–1.66] and adjusted HR 1.55, 95% CI [1.30–1.85], respectively; both p &lt; 0.0001). Adjusted models for LACI showed significant improvement in model discrimination and reclassification compared to currently used HF risk score model for predicting HF incidence (C-statistic: 0.81 vs. 0.77; NRI = 0.411; IDI = 0.043). After adjustment, ΔLACI showed also significant improvement in model discrimination compared to the multivariable model with traditional MESA-HF risk factors for predicting incident HF (C-statistic: 0.82 vs. 0.77; NRI = 0.491; IDI = 0.058).Conclusions: In a multi-ethnic population, atrioventricular coupling (LACI), and coupling change (ΔLACI) are independently associated with incident HF. Both have incremental prognostic value for predicting HF events over traditional HF risk factors.

Prognostic value of heart rate reserve in patients with suspected coronary artery disease undergoing stress myocardial perfusion imaging

Background Chronotropic incompetence is common in patients with cardiovascular disease and is associated with increased risk of adverse events. We assessed the incremental prognostic value of heart rate reserve (HRR) over stress myocardial perfusion single-photon emission computed tomography (MPS) findings in patients with suspected coronary artery disease (CAD). Methods We studied 866 patients with suspected CAD undergoing exercise stress-MPS as part of their diagnostic program. The primary study endpoint was all-cause mortality. All patients were followed for at least 5 years. HRR was calculated as the difference between peak exercise and resting HR, divided by the difference of age-predicted maximal and resting HR and expressed as percentage. Results During 7 years follow-up, 61 deaths occurred, with a 7% cumulative event rate. Patients experiencing death were older (P < .001), and had a higher prevalence of male gender (P < .001) and diabetes (P < .05). Patients with event also had lower values of HRR (65% ± 27% vs 73% ± 18%, P < .0001) and higher prevalence of stress-induced myocardial ischemia (25% vs 8%, P < .0001). Male gender, HRR and stress-induced ischemia were independent predictors of all-cause mortality (all P < .01). HRR improved the prognostic power of a model including clinical data and MPS findings, increasing the global χ2 from 66 to 82 (P < .005). Conclusions Chronotropic incompetence has independent and incremental prognostic value in predicting all-cause mortality in patients with suspected CAD undergoing exercise stress-MPS. Hence, the evaluation of HRR may further improve patients’ risk stratification.