Abozied, Omar

Abstract Aims Echo-derived left atrial (LA) stiffness index improves prognostication in patients with heart failure preserved ejection fraction but has not been studied in adults with repaired coarctation of aorta (COA). We hypothesized that, among adults with COA, those with high LA stiffness index would have worse disease severity indices [peak VO2, NT-proBNP, and right ventricular to pulmonary artery (RV-PA) coupling], heart failure hospitalization, and all-cause mortality. Methods and results LA stiffness index was estimated using the baseline echocardiogram as the quotient of septal E/e′ and LA reservoir strain (E/e′/LARS). Using the median septal LA stiffness index as the cut-off, patients were divided into high LA stiffness index (LA stiffness index >0.28) vs. low LA stiffness index groups (LA suggests index ≤0.28). The study comprised of 729 patients [age 36 ± 16 years; males 437 (60%)]. LA stiffness index correlated with RV-PA coupling (r = −0.56, P < 0.001), NT-proBNP (r = 0.62, P < 0.001), and predicted peak VO2 (r = −0.51, P < 0.001). High LA stiffness index was associated with heart failure hospitalization (adjusted HR 3.17, 95% confidence interval (CI) 1.84–7.36, P = 0.007) and all-cause mortality (adjusted HR 2.81, 95% CI 1.28–12.32, P = 0.005). LA stiffness index had superior prognostic performance for predicting 5-year risk of heart failure hospitalization (AUC 0.803, 95% CI 0.756–0.849, P < 0.001) and all-cause mortality (AUC 0.786, 95% CI 0.742–08.30, P < 0.001) compared with conventional echocardiographic indices of left heart diastolic function. Conclusion LA stiffness index improves prognostication in adults with COA and can potentially be used to guide timing of intervention or monitor response to therapy.

BACKGROUND: The purpose of this study was to assess the feasibility and prognostic value of cardiac output (CO) reserve assessment using exercise echocardiography in Fontan patients. We hypothesized that adults with Fontan palliation had lower CO reserve compared with controls, and impaired CO reserve was associated with greater congestion (NT-proBNP [N-terminal pro-B-type natriuretic peptide]) and cardiovascular events (death/transplant/heart failure hospitalization) in Fontan patients. METHODS: Thirty-seven Fontan patients and 61 controls underwent exercise echocardiography using a supine cycle ergometer. Doppler-derived CO and oxygen consumption (VO 2 ) were assessed at rest and every stage of exercise. CO reserve was calculated as ∆CO/Watt (∆CO/W) and ∆CO/∆VO 2 . RESULTS: Assessment of CO reserve was feasible in 95% of the Fontan group with modest reproducibility. Although both groups had similar CO at rest, the Fontan group had lower CO reserve with exercise as evidenced by lower ∆CO/W ratio (46±17 versus 57±19 mL/W; P <0.001) and lower ∆CO/∆VO 2 ratio (4.48±1.02 versus 5.37±2.18 mL/mL; P =0.03). There was a correlation between ∆CO/W ratio and log NT-proBNP (r=0.65; P <0.001), and between ∆CO/∆VO 2 ratio and log NT-proBNP (r=0.53; P =0.009). Impaired CO reserve was associated with congestion and cardiovascular events and provided improved prognostication (higher area under the curve and C statistics) above conventional echocardiographic indices and treadmill peak VO 2 . CONCLUSIONS: Patients with Fontan palliation had lower CO reserve, and impaired CO reserve was associated with congestion and cardiovascular events. Further studies are required to determine whether cardiac interventions can improve CO reserve and whether changes in CO reserve can be used as a surrogate end point for therapeutic response.

Background: Patients with Fontan palliation have reduced aerobic capacity because of impaired cardiac, pulmonary, and skeletal muscle function. However, the assessment of aerobic capacity in this population still relies on comparisons with people without cardiovascular disease, rather than comparison with the expected aerobic capacity of other Fontan patients. The purpose of this study was to determine the expected aerobic capacity of adults with Fontan palliation. Method: Adults with Fontan palliation who underwent cardiopulmonary exercise test at Mayo Clinic (2003-2023) were stratified into quartiles based on the predicted peak VO 2 . We assessed the correlates of predicted peak VO 2 , and the relationship between predicted peak VO 2 quartiles and cardiovascular outcomes (death/transplant). Results: Of 323 patients (age 29±9 years; 177 [55%] men), the median peak VO2 was 19.1 (15.2 - 23.9) ml/kg/min, and this corresponds to a predicted peak VO 2 of 51% (range 19 -88; interquartile range 41 - 62). The correlates of higher predicted peak VO 2 were smaller body mass index, higher systemic saturation, and lower Fontan pressures. The top, 2 nd ,3 rd , and bottom quartile of predicted peak VO 2 corresponds to predicted peak VO 2 of 63-88%, 51-62%, 41-50%, and 19-40%, respectively. Using the top quartile as the reference, the 3 rd quartile (HR 1.13, 95% CI 1.03-1.28, p=0.02), and 4 th quartile were associated with a higher risk of death/transplant (HR 1.32, 95% CI 1.16-1.69, p<0.001). Conclusions: The results of the current study would help calibrate the interpretation of exercise test data in adults with Fontan palliation and improve risk stratification in this population.

Abstract Purpose To assess incidence and risk factors for anthracycline-induced left ventricular dysfunction, and associated mortality in order to inform patients and providers of the risk, as well as for clinical trial endeavours. Background Anthracyclines (ACs) are very effective cancer therapeutics, but their use is confronted by the risk of cardiotoxicity. Estimates of AC-induced cardiotoxicity based on systematic analyses are limited and have not recently been defined. We present here a systematic review and meta-analysis of the incidence of anthracycline induced subclinical (AC-LVD) and clinical LV dysfunction (AC-CHF) and AC-CHF related mortality in non-liposomal AC recipients over the last 3 decades. Methods We searched Ovid MEDLINE(R), Embase, Cochrane Database and other major databases from their inception until June 22, 2023 for studies examining the rate of AC induced cardiomyopathy in patients receiving ACs and anthraquinones for haematologic, breast (BC) and sarcomatous malignancies. Covidence was used to aid with the management of our systematic review. Screening of abstracts and data extraction was independently performed by 2 reviewers. Results 6,365 abstracts were reviewed, of which 74 were included in the final analysis. 72 studies (n=41,138) reported data on AC-LVD, and 47 studies (n=27,012) reported data on AC-CHF. The average age was 53 years and 50% of the patients were female. Data on cardiac function at baseline was available in only 70% of the studies. Overall, AC-LVD occurred in 8.2% (95% CI 6.8%-10.2% I2 97%) (Fig 1). AC-CHF was noted in 2.2% (95% CI 1.6% to 2.9%, I2 91%) (Fig 2A), mortality related to decompensated AC-CHF was 0.5% (95% CI 0.3%-0.9%, I2 88%) (Fig 2B) while total mortality rate among AC recipients was 24.9% (95% CI 14.8-38.7%, I2 99%). Incidence of AC-LVD was higher in doxorubicin recipients (vs other ACs 10.5% vs 5-5.6%), studies from North America & Asia (vs other regions; 9.3-9.6% vs 6.7%), and prospective studies (vs retrospective studies; 8.7% vs 7.5%). AC-LVD was more common in BC patients (vs other cancers; 8.7% vs 3.5-7.2%) while AC-CHF was more common in lymphoma patients (8.5% vs 1.6-4.1%). AC-LVD was 4.6 times (95% CI 1.2-17.1, p=0.02) more likely in patients with a mean age &gt;70 (vs &lt;70). 21 definitions for AC-LVD were used across the studies. The most common definition (15 studies; n=7904) was "any decline in LVEF from baseline" resulting in a 5.8% rate of AC-LVD. Conclusions AC-LVD and AC-CHF has been reported in up to 10% and 3% of AC recipients, respectively. AC-CHF related mortality occurs in &lt;1% of anthracycline recipients and has a 2-3% share in overall mortality among these patients. The type of malignancy and anthracycline can influence the rate of AC-LVD, AC-CHF and AC-CHF related mortality. Global region, age of the patient population and study design also seem to influence incidence rates. There is noteworthy heterogeneity in definitions for cardiotoxicity across studies.

Background There are limited data about the impact of timing of pulmonary valve replacement (PVR) on right heart reverse remodeling in patients with pulmonary regurgitation following intervention for isolated pulmonary valve stenosis (PS). This study compared differences in postprocedural right heart reverse remodeling after early versus late PVR (defined as PVR before versus after attainment of the conservative consensus criteria proposed by Bokma et al, 2018) in patients with prior intervention for PS, using patients with tetralogy of Fallot as the reference group. Method and Results Right atrial reservoir strain and right ventricular free wall strain was measured at baseline, 1 and 3 years after PVR. There were 114 patients with PS (early PVR, 87 [76%]; late PVR, 27 [24%]) and 291 patients with tetralogy of Fallot (early PVR, 197 [67%]; late PVR, 96 [33%]). The PS group had greater improvement in right atrial reservoir strain at 1 year (12%±4% versus 8%±4%; P <0.001) and 3 years (15%±6% versus 9%±6%; P <0.001), and a greater improvement in right ventricular free wall strain at 1 year (12%±4% versus 7%±3%, P =0.008) and 3‐years (16%±6% versus 12%±5%; P =0.01) after PVR compared with the tetralogy of Fallot group. There was no difference in right heart reverse remodeling between patients who underwent early versus later PVR within the PS group. In contrast, late PVR was associated with less right heart reverse remodeling within the tetralogy of Fallot group. Conclusions These data suggest that patients with palliated PS presenting pulmonary regurgitation have a more benign clinical course, and hence delaying PVR in this population may be appropriate.

Introduction: The relative diagnostic and prognostic performance of left ventricular global longitudinal strain (LVGLS) as compared to LV ejection fraction (LVEF), and the role of LVGLS for detecting early stages of LV systolic dysfunction in adults with repaired coarctation of aorta (COA) is unknown. Objective: The purpose of this study was to address these knowledge gaps. Methods: Retrospective cohort study of adults with repaired COA that underwent transthoracic echocardiogram (2003-2020). LV systolic function was assessed using LVEF (derived from volumetric analysis) and LVGLS (derived from speckle-tracking echocardiography). Results: Of the 795 patients (age 36±14 years), mean LVEF and LVGLS were 62±11%, and 21±4%, respectively. The prevalence of LV systolic dysfunction was higher when assessed using LVGLS as compared to LVEF (20% versus 6%, p<0.001). Of 795 patients, 94 (12%) patients died, of which 75 (9%) died from cardiovascular causes. LVGLS provided more robust prognostic power in predicting all-cause mortality as compared to LVEF as evidenced by a higher C -statistic (0.743, 95%CI 0.730-0.755 versus 0.782, 95% CI 0.771-0.792, p<0.001). Furthermore, patients with normal LVEF in the setting of reduced LVGLS had a higher risk of all-cause mortality (as compared to patients with normal LVGLS and LVEF) and were at risk for temporal decline in LVEF during follow-up. Conclusions: These findings suggest that the use of LVGLS for risk stratification can help identify high-risk patients, and provide opportunities for interventions, which would, in turn, improve clinical outcomes. Further studies are required to empirically test these postulates.

Introduction: Right ventricular (RV) systolic dysfunction and pulmonary hypertension is present in 20% of adults with repaired coarctation of aorta (COA). However, the prognostic value of RV to pulmonary artery (RV-PA) coupling in this population is unknown. Objective: The purpose of this study was to assess the relationship between RV-PA coupling and clinical outcomes (heart failure hospitalization and all-cause mortality) in this population. Methods: Retrospective cohort study of adults with repaired COA and normal RV systolic function defined as RV-free wall strain ≥-24%. RV-PA coupling was assessed using tricuspid annular plane systolic excursion/ RV systolic pressure (TAPSE/RVSP) ratio. Results: Of 509 patients (median age 32 [20-45] years; men 290 [57%]), the average TAPSE and RVSP were 22±5 mm and 33±9 mmHg, respectively, and TAPSE/RVSP ratio was 0.78 (0.56-0.96) mm/mmHg. Of 509 patients, 51 (10%) died and 43 (8%) were hospitalized for heart failure. TAPSE/RVSP was associated with all-cause mortality (hazard ratio 0.82, 95% confidence interval 0.78-0.86, per 0.1 mm/mmHg), and heart failure hospitalization (hazard ratio 0.86, 95% confidence interval 0.79-0.83, per 0.1 mm/mmHg) after adjustment for anatomic lesions, cardiovascular interventions, comorbidities, and echocardiographic indices. The inclusion of TAPSE/RVSP ratio in the risk models improved the prognostic power of the models to predict all-cause mortality (C-statistics difference 0.046, p<0.001), and heart failure hospitalization (C-statistics difference 0.031, p=0.007). Conclusions: TAPSE/RVSP ratio was associated with outcomes in COA patients with normal RV systolic function, suggesting that abnormal RV-PA coupling may be present prior to the onset of overt RV systolic function in this population.

Introduction: Adults with repaired tetralogy of Fallot (TOF) have right atrial (RA) remodeling and dysfunction, and RA function can be measured using speckle-tracking echocardiography. There is limited data about the role of RA strain imaging in risk stratification in this population. Hypothesis: We hypothesized that RA reservoir strain could identify TOF patients at risk of developing atrial arrhythmia. We assessed the relationship between RA reservoir strain and atrial arrhythmias in adults with repaired TOF to test this hypothesis. Methods: Retrospective cohort study of adults with repaired TOF, and no prior history of atrial arrhythmias. Atrial arrhythmia was defined as atrial fibrillation, atrial flutter/atrial tachycardia, and categorized as new onset versus recurrent atrial arrhythmias. Results: We identified 426 patients (age 33±12 years; males 208 (49%)) that met the inclusion criteria. The mean RA reservoir, conduit, and booster strains were 34±11%, 20±9%, and 15±12%, respectively. Of 426 patients, 73 (17%) developed new-onset atrial arrhythmias (atrial flutter/tachycardia n=42; atrial fibrillation n=31); annual incidence 1.9%. RA reservoir strain was associated with new-onset atrial arrhythmias (adjusted HR 0.95, 95% CI 0.93-0.97) after multivariable adjustment. Of 73 patients with new-onset atrial arrhythmia, 41 (56%) had recurrent atrial arrhythmia (atrial flutter/tachycardia n=18; atrial fibrillation n=23); annual incidence 11.2%. Similarly, RA reservoir strain was associated with recurrent atrial arrhythmias (adjusted HR 0.92, 95% CI 0.88-0.96) after multivariable adjustment. Conclusions: RA strain indices can identify patients at risk for atrial arrhythmias, and this can, in turn, be used to guide the type/intensity of therapy in such patients.

BACKGROUND: There are limited data about changes in cardiac function (cardiac reverse remodeling) and heart failure indices after transcatheter tricuspid valve-in-valve replacement (TT-VIVR). The purpose of this study was to evaluate cardiac reverse remodeling and temporal changes in heart failure indices after TT-VIVR in adults with congenital heart disease. METHODS: Retrospective cohort study of adults with congenital heart disease that underwent TT-VIVR and had >6 months of follow-up (January 1, 2011, to April 30, 2023). Echocardiographic indices of cardiac remodeling and heart failure indices (New York Heart Association class, NT-proBNP (N-terminal pro-brain natriuretic peptide), glomerular filtration rate, and model for end-stage liver disease excluding international normalized ratio score) were assessed preintervention and at 1-, 3-, and 5-year postintervention. RESULTS: Of 39 patients (age 39 [32–46] years), 14 (36%) and 25 (64%) received Melody valve and Sapien valve prosthesis, respectively. At 1-year post-TT-VIVR, there was a temporal improvement in right atrial reservoir strain (17±8% versus 22±8%, P <0.001), right atrial volume (81 [59–108] versus 63 [48–82] mL/m 2 , P <0.001), right atrial pressure (12±4% versus 6±4%, P <0.001), and right ventricular global longitudinal strain (−15±7% versus −20±7%, P <0.001). Similarly, there was a temporal improvement in NT-proBNP, glomerular filtration rate, model for end-stage liver disease excluding international normalized ratio score, and New York Heart Association class. The temporal improvements in heart failure indices and valve function were maintained at 3- and 5-year post-TT-VIVR. CONCLUSIONS: Considering the significant mortality risk associated with reoperations for tricuspid valve replacement, these data suggest favorable outcomes after TT-VIVR, and support TT-VIVR as a viable alternative to surgical tricuspid valve replacement, especially in high-risk patients.

BACKGROUND: The prognostic role of the congenital heart disease (CHD) anatomic/physiologic classification has not been systematically studied. The purpose of this study was to determine whether CHD physiologic stage provided improvement in prognostic power (to predict all-cause mortality) beyond conventional clinical risk models. METHODS: Retrospective study of adults with CHD at the Mayo Clinic (2003–2019). The CHD physiologic stage was assessed at baseline and 36 (24–48) months, and patients were classified into stages A to D at these time points. Clinical stability (remaining in the same stage), clinical improvement (moving to less advanced stage), and clinical deterioration (moving to more advanced stage) were determined at 36 months. We defined conventional clinical risk indices as age/sex, functional class, comorbidities, cardiac procedures, hepatorenal dysfunction, and ventricular/valvular dysfunction. RESULTS: Of 5321 patients, 1649 (31%), 1968 (37%), 1224 (23%), and 480 (9%) were in stages A, B, C, and D at baseline. Of 5321 patients, 4588 (86%) also had assessments at 36 months, and of these patients, 3347 (73%), 386 (8%), and 855 (19%) had clinical stability, deterioration, and improvement, respectively. Patients with clinical improvement were more likely to have undergone cardiac procedures between both assessments. Both baseline CHD physiologic stage (hazard ratio, 1.13 [95% CI, 1.09–1.17]; P <0.001, per unit increase in stage) and change in CHD physiologic stage (hazard ratio, 1.46 [95% CI, 1.32–1.61]; P =0.007, per unit increase in stage) were associated with mortality after adjustments for conventional risk indices and provided incremental improvement in prognostic power beyond conventional clinical risk models as evidence by an increase in C statistic from 0.702 (0.681–0.724) to 0.769 (0.754–0.787). CONCLUSIONS: The CHD physiologic stage can potentially be used for risk stratification, as well as to monitor disease progression and response to therapy.