Al-Shakarchi, Nader

Background Transthyretin amyloid cardiomyopathy (ATTR‐CM) has a specific pathophysiology, with myocardial stiffening and systolic dysfunction only in advanced stages. We aimed to investigate the response to cardiac resynchronization therapy (CRT) in ATTR‐CM compared with heart failure. Methods In this multicenter, observational study, patients with ATTR‐CM receiving CRT (n=101) were matched to patients without amyloid cardiomyopathy by sex, age, and implantation type (CRT with versus without defibrillator versus conduction system pacing, upgrade versus first implant). We evaluated changes in QRS duration and echocardiographic parameters following CRT implantation and at the most recent available assessments. The study end points were all‐cause death alone or combined with heart failure hospitalization. Results Patients with ATTR‐CM (median age, 76 [interquartile range, 72–83] years, 98% men, left ventricular (LV) ejection fraction 30% [26–33]) showed greater QRS shortening after CRT implantation ( P =0.012), but not after a median of around 1 year ( P =0.152). There were no significant differences in the absolute LV ejection fraction changes immediately after implantation (+7 [+2/+10] versus +3 [0/+9] units; P =0.124), or to the last echo ( P =0.796), which was performed after 1.3 years in patients with ATTR‐CM and 2.9 years in patients without amyloid cardiomyopathy. Patients with ATTR‐CM had a shorter survival than controls ( P <0.001 for both end points). Patients with ATTR‐CM experiencing an early improvement in LV ejection fraction had a longer survival (log‐rank, 4.3; P =0.038). Conclusions Following CRT implantation, patients with ATTR‐CM show QRS narrowing and improvement in LV ejection fraction, not different from patients without amyloid cardiomyopathy. Early favorable LV remodeling seems to be associated with a lower risk of all‐cause death.

Background: Carcinoid heart disease (CaHD) typically affects tricuspid and pulmonary valves and is associated with poor survival. To date, the role of right ventricular (RV) and atrial (RA) strain has not been evaluated in such cohort. Research Questions: To evaluate RV and RA strain patterns and assess their impact on survival and congestive heart failure (CHF) development. Methods: Retrospective study of CaHD patients (ICD 9/10 diagnosis of neuroendocrine tumor and echocardiographic evidence of CaHD prior to any surgical intervention; 2004-2019). Longitudinal strain was evaluated using speckle-tracking, RV/RA-focused view was used. RV strain was averaged from 3 and 6 segments for free wall (FWS) and global strain (GS), respectively. Auto-tracking with manual adjustment was done to ensure optimal tracking. The tracing of RV/RA endocardium was done with 15 points using the tricuspid valve annulus as a reference. The impact of strain parameters on mortality and CHF was evaluated with the Kaplan Meier and Cox proportional hazard analyses. Results: A total of 138 patients were included (mean age was 63 ± 10 years; 47% females). Median follow-up was 5.0 years (3.7-8.2). Significant RA and RV enlargement (72 and 79%, respectively) was more common than RV dysfunction (10%). The most common valvular disease > moderate was tricuspid regurgitation (TR; 97%) followed by pulmonary regurgitation (PR; 70%). RV GS mean was -21 + 6%, with FWS of -23 + 7%. The mean RA strain analysis revealed (93% sinus rhythm): a reservoir of 26 + 11%, a conduit of 14 + 8%, and an atrial contraction of 12 + 8%. Strain parameters were not associated with overall mortality. As opposed to PR/TR severity and RV/RA enlargement/dysfunction, patients with low RA reservoir strain (<23%) were more likely to develop CHF (adjusted-HR=1.80, p=0.04, 95% CI 1.04 - 3.134). Conclusions: Our findings suggests that CaHD patients have RV/RA dysfunction with overall reduced strain parameters. Patients with low RA reservoir had higher risk of CHF, but none of the RV/RA strain parameters were associated with excess mortality. This shows how strain analysis could complement other echocardiographic parameters in CaHD morbidity assessment.

Background: Transthyretin cardiac amyloidosis (ATTR-CA) carries an elevated risk of developing ventricular arrhythmias (VA) but there remains limited evidence supporting the role of catheter ablation in this population. Purpose: To assess the safety and efficacy of catheter ablation for VA in ATTR-CA. Methods: An electronic database was used to identify all patients suspected of having ATTR-CA who underwent catheter ablation for VA at our institution between January 2010 and December 2023. Patients who did not meet the diagnosis of ATTR-CA and had a negative workup who underwent catheter ablation for ventricular tachycardia (VT) or premature ventricular contractions (PVCs) were used to form a control group matched for age, sex and left ventricular ejection fraction at a ratio of 2:1. Results: 20 controls and 10 cases of ATTR-CA were identified. Examining the two groups at baseline (Table 1), the mean age at index ablation was 67.7±7.0 and 68.6±8.1 years (p=0.359), mean follow-up time was 4.1±3.1 and 4.2±2.6 years (p=0.494), and the proportion of males was 100% and 90% respectively. The ATTR-CA group had a significantly higher proportion of chronic kidney disease (90% vs. 50%, p=0.032) and prior stroke or thrombotic events compared to the control group (50% vs. 10%, p=0.026) with similar CHA 2 DS 2 VASc scores (4.2±1.6 vs. 3.8±1.3, p=0.233). Both groups had comparable left ventricular ejection fraction (41.4%±14% vs. 46.9%±15.2%, p=0.173), VT/PVCs at presentation (40%/60% vs. 25%/75%, p=0.77), use of antiarrhythmics (70% vs. 60%, p=0.592), and high proportion of atrial fibrillation/flutter (70% vs. 90%, p=0.168). Procedural (261.2±101.2 vs. 265.7±125.6 mins, p=0.449) and total energy delivery time (1442.9±1509.1 vs. 1744.6±956.2 secs, p=0.296) was not significantly different in the two groups. Both groups had a significant decrease in PVC burden postablation with a reduction from 26.8% to 3.8% (p=0.024) and from 27.1% to 13.6% (p=0.028) in the ATTR-CA and control group respectively. A downward trend was seen in antitachycardia pacing events for VT postablation in the ATTR-CA (14.7±9.8 vs. 5.3±6.7, p =0.184) and control (193±387.6 vs. 0.67±1.2. p=0.139) groups. No major complications occurred after ablation (Table 2). Mean time to recurrence post-index ablation was similar between both groups (1620.4±483.8 vs. 1498.8±291.4 days, p=0.987, Figure 1). Conclusions: Catheter ablation appears to be safe and effective for VT and PVCs in patients with ATTR-CA.

Abstract Aims Aortic stenosis (AS) is a common and progressive disease, which, if left untreated, results in increased morbidity and mortality. Monitoring and follow-up care can be challenging due to significant variability in disease progression. This study aimed to develop machine learning models to predict the risks of disease progression and mortality in patients with mild AS. Methods and results A comprehensive database including 9611 patients with serial transthoracic echocardiograms was collected from a single institution across three clinical sites. The data set included parameters from echocardiograms, electrocardiograms, laboratory values, and diagnosis codes. Data from a single clinical site were preserved as an independent test group. Machine learning models were trained to identify progression to severe stenosis and all-cause mortality and tested in their performance for endpoints at 2 and 5 years. In the independent test group, the AS progression model differentiated those with progression to severe AS within 2 and 5 years with an area under the curve (AUC) of 0.86 for both. The feature of greatest importance was aortic valve mean gradient, followed by other valve haemodynamic measurements including valve area and dimensionless index. The mortality model identified those with mortality within 2 and 5 years with an AUC of 0.84 and 0.87, respectively. Smaller reduced-input validation models had similarly robust findings. Conclusion Machine learning models can be used in patients with mild AS to identify those at high risk of disease progression and mortality. Implementation of such models may facilitate real-time, patient-specific follow-up recommendations.

Abstract Aims The viability of cardiac resynchronization therapy (CRT) in inotrope-dependent heart failure (HF) has been a matter of debate. Methods and results We searched Medline, EMBASE, Scopus, and the Cochrane Library until 31 December 2022. Studies were included if (i) HF patients required inotropic support at CRT implantation; (ii) patients were ≥18 years old; and (iii) they provided a clear definition of ‘inotrope dependence’ or ‘inability to wean’. A meta-analysis was performed in R (Version 3.5.1). Nineteen studies comprising 386 inotrope-dependent HF patients who received CRT (mean age 64.4 years, 76.9% male) were included. A large majority survived until discharge at 91.1% [95% confidence interval (CI): 81.2% to 97.6%], 89.3% were weaned off inotropes (95% CI: 77.6% to 97.0%), and mean discharge time post-CRT was 7.8 days (95% CI: 3.9 to 11.7). After 1 year of follow-up, 69.7% survived (95% CI: 58.4% to 79.8%). During follow-up, the mean number of HF hospitalizations was reduced by 1.87 (95% CI: 1.04 to 2.70, P &lt; 0.00001). Post-CRT mean QRS duration was reduced by 29.0 ms (95% CI: −41.3 to 16.7, P &lt; 0.00001), and mean left ventricular ejection fraction increased by 4.8% (95% CI: 3.1% to 6.6%, P &lt; 0.00001). The mean New York Heart Association (NYHA) class post-CRT was 2.7 (95% CI: 2.5 to 3.0), with a pronounced reduction of individuals in NYHA IV (risk ratio = 0.27, 95% CI: 0.18 to 0.41, P &lt; 0.00001). On univariate analysis, there was a higher prevalence of males (85.7% vs. 40%), a history of left bundle branch block (71.4% vs. 30%), and more pronounced left ventricular end-diastolic dilation (274.3 ± 7.2 vs. 225.9 ± 6.1 mL). Conclusions CRT appears to be a viable option for inotrope-dependent HF, with some of these patients seeming more likely to respond.

Abstract Background Isolated tricuspid regurgitation (TR) repair or replacement carries significant operative mortality risk mainly due to delayed referral. We have recently developed the Tricuspid Regurgitation Impact on Outcomes (TRIO) score to assess risk in TR based on 8 simple variables (age, sex, severe TR, creatinine&gt;2 mg/dl, history of heart failure, history of chronic lung disease, AST &gt;40 units/L, heart rate &gt;90). Whether this score can be used in assessment of TR surgical risk and long term outcome is unknown. Purpose To examine the impact of TRIO scores on the postoperative outcomes of isolated tricuspid valve surgery. Methods Adult patients with severe functional TR who underwent isolated tricuspid valve replacement or repair between 2000-2022 were identified. Postoperative outcomes were compared across low (0-3), intermediate (4-6), and high (7-12) TRIO risk score groups. Results 177 patients were included. Mean age was 70.7 ± 12.2 years, 69 (39%) were male, 34 (19%) were low TRIO score, 111 (63%) intermediate score and 32 (18%) high score. Tricuspid repair was performed in 43 (24.3%) and valve replacement in 134 (75.7%), reflecting the advanced disease stages of this patient cohort. At short term, higher TRIO scores were associated with more frequent need for urgent surgery, prolonged ventilation (&gt;72h) and postoperative dialysis (p&lt;0.05 for all). Perioperative 30-day mortality increased with the TRIO risk score (low: 0%; intermediate: 4.5%; high: 9.4%) but differences did not reach statistical significance (p=0.187). Low risk patients had a shorter hospital and ICU stay (Figure 1A-B). During a mean follow-up of 5.2 ± 3.2 years, 98 (55.4%) patients died. At long term follow-up, lower TRIO scores were associated with improved survival after tricuspid surgery (Figure 1C). Conclusions Patients with higher TRIO scores have more postoperative complications, require longer hospital stay and have higher all-cause mortality at long-term follow-up. Our findings suggest that TRIO score may also be used for risk stratification in patients considered for surgical management of isolated functional TR.

Abstract Background Inotrope-dependent heart failure (HF) carries a poor prognosis. Advanced mechanical supports have been viewed as primary treatment modalities for these patients, but cardiac resynchronization therapy (CRT) is an emerging alternative. Whether CRT is viable in HF patients who require inotropic support is uncertain. Purpose To assess outcomes of CRT in end-stage inotrope-dependent HF. Methods Following PRISMA guidelines, we searched Medline, EMBASE, Scopus, and Cochrane Library until December 31st 2022, with the following terms: "end-stage heart failure," "catecholamine-dependent overt heart failure," "inotrope-dependent heart failure," "advanced heart failure," "New York Heart Association class IV," "NYHA class IV." These terms were combined with "cardiac resynchronization therapy" OR "CRT" OR "biventricular device". Studies were included if: 1) HF patients required on inotropic support at CRT implantation; 2) patients were at least 18 years old; and 3) provided a clear definition of "inotrope dependence" or "inability to wean." A meta-analysis with random effects was performed in R (Version 3.5.1) with data presented as mean ± standard error. Results 19 studies comprised of 386 inotrope-dependent HF patients (mean age 64.4 ± 1.2 years, 76.9% male, 54.6% non-ischemic cardiomyopathy, mean QRS duration 168.0 ± 4.6 ms, mean follow-up 778 ± 110.7 days) were included for meta-analysis. A large majority of patients survived until discharge at 90% (95% CI: 81.0%-96.8%, I2=51%, p=0.04, Figure 1A), 88.6% were weaned off inotropes (95% CI: 77.5%-96.8%, I2=64%, p&lt;0.01), and mean time to discharge post-CRT was 7.8 days (95% CI: 3.9-11.7, I2= 84%, p&lt;0.01). After one year of follow-up 69.5% survived (95% CI: 59.2%-78.9%, I2=53%, p=0.02, Figure 1B) and 59.1% (95% CI: 50.1%-67.8%, I2=58%, p&lt;0.01, Figure 1C) were alive at the end of follow-up. During follow-up the mean number of hospital admission for HF was reduced by 1.87 (95% CI: 2.70-1.04, I2=77%, p=0.04). Post-CRT mean QRS duration was reduced by 29.0 ms (95% CI: 41.33-16.68, I2=69%, p=0.006, Fig) and mean left ventricular ejection fraction increased by 4.83% (95% CI: 3.09%-6.57%, I2=16%, p=0.31, Fig). The mean NYHA class post-CRT was 2.7 (95% CI: 2.5-3.0, I2=56%, p=0.03, Figure 2A), 39.6% (95% CI: 18,.7%-62.3%, I2=83%, p&lt;0.01, Figure 2C) improved to NYHA class III and 34.6% (95% CI: 16.4%-55.2%, I2=79%, p&lt;0.01, Figure 2D) improved to NYHA class II. Responders to CRT tended be male (85.7% vs. 40%, p=0.015), have a history of left bundle branch block (71.4% vs. 30%, p=0.036) or an increased left ventricular end-diastolic volume (274.3 mL vs. 225.9 mL, p=0.038). Conclusion(s) Our results suggest that CRT is an alternative option for end-stage inotrope-dependent HF, improving survival, NYHA status, and HF readmission. CRT responders appear to be male with evidence of preserved diastolic function or a history of a left bundle branch block.