Lin, Grace

Background: Cardiac amyloidosis (CA) is associated with sinus node dysfunction (SND) and conduction system disease (CSD) yet data on pacing indications and outcomes is scarce. Methods: Retrospective review of patients (pts) with CA who had device implantation due to pacing indication at our institution. Results: At total of 51 (mean age 67.2±9.2 years, 90.2% male) pts with immunoglobulin light chain (n=27, 52.9%), hereditary transthyretin (n=7, 13.7%) and wild-type transthyretin (n=17, 33.3%) CA were included. Indication for pacing was exercise intolerance (n=16, 31.4%), syncope (n=16, 31.4%), congestive heart failure (n=5, 9.8%) and palpitation (n=2, 3.9%) with SND (n=23, 45.1%), CSD (17=33.3%) and uncontrolled atrial fibrillation (n=11, 21.6%). 16 (31.4%) pts received defibrillators (ICD) for primary prevention, of whom 8 (15.7%) had left ventricular ejection fraction (LVEF) ≤35%. Atrial (P wave: 1.7±1.2mV, threshold: 1.1±0.5mV/0.5±0.2ms) and right ventricular (RV) (R wave: 7.9±3.8mV, threshold: 0.8±0.4mV/0.4±0.1ms) lead parameters were satisfactory at implantation. During follow-up (mean 36.6±33.6 months), 26 (51%) pts reported symptomatic improvement (SI). Syncope was the only predictor of SI (OR 16.4, 95%CI 1.8-145.2, p=0.01) while exercise intolerance was not (OR 0.09, 95%CI 0.02-0.44, p=0.003). First-time life-threatening ventricular arrhythmias (VA) occurred in 6 (11.8%) pts, 3 (5.9%) had ICD implanted for LVEF ≤35%, 3 (5.9%) without ICD and LVEF ≥35%. Syncope was not predictive of first-time VA. RV lead noise led to inappropriate ICD shocks in 1 patient. Atrial lead sensing failure occurred in 6 (11.8%) and loss of capture in 5 (9.8%). Conclusion: Device implantation in patients with cardiac amyloidosis is safe but atrial lead failure is common. Syncope usually improves with pacing whereas other factors should be considered in those presented with exercise intolerance. Selection of pts who need pacing for prophylactic ICD implantation is challenging as neither left ventricular ejection fraction nor syncope are predictive of arrhythmic events.

Background: Clinically significant tricuspid regurgitation (TR) is an important contributor to morbidity and mortality. The Tricuspid Regurgitation Impact on Outcomes (TRIO) score based on 8 parameters (age, gender, chronic heart failure, chronic lung disease, heart rate, creatinine, aspartate transaminase level, and TR severity) is used for risk stratification. The performance of the TRIO score in patients with TR secondary to severe pulmonary hypertension (PH) is unknown. Research Questions: To evaluate whether the TRIO score can be applied in patients with TR and pulmonary hypertension (PH), and to identify other predictors of mortality. Methods: Retrospective study including patients with TR ≥ moderate. Severe PH was defined as right ventricular systolic pressure (RVSP) ≥50 mmHg. The impact of clinical, echocardiographic and laboratory variables on mortality was evaluated with the Cox proportional hazard method. Results: A total of 13,482 patients from the TRIO population were included; severe PH was present in 6,530 (48.4%); mean age 73.4 + 13.3, 55.7% females. TRIO score performance was modest (AUC 0.62) in risk stratification (Figure A). PH patients had significantly higher mortality than those without PH at all levels of TRIO score (Figure B); differences were progressively lower with increasing TRIO scores. At multivariate analysis, only TRIO score [HR = 1.54 (1.35-1.77) per unit change], presence of an elevated NT-proBNP [HR = 1.02 (1.02-1.03) per 1000 pg/ml change], RVSP (HR = 1.08 (1.02-1.16) per 10 mmHg change], presence of RV dysfunction [HR = 1.15, (1.05-1.26)] and pulmonary artery pulsatility index (PAPi) ≤ 4 [HR = 1.34 (1.07-1.67)] were significant predictors of mortality (model AUC 0.65). Conclusions: TRIO score allows risk stratification in PH patients, but performance is modest; incorporating additional factors marginally increased model performance. PH patients have higher mortality at all levels of TRIO score, more so at low scores.

Introduction: Isolated functional tricuspid regurgitation (FTR) in the absence of structural heart disease may develop secondary to elevation in left heart pressures caused by left ventricular diastolic dysfunction (DD), as in heart failure with preserved ejection fraction (HFpEF). FTR may also herald the presence of occult DD or indicate greater risk for new-onset DD. However, prevalence and incidence of diastolic dysfunction (DD) in isolated FTR have not been studied. Aims: Investigate the prevalence and incidence of DD across the different severities of FTR of unclear cause. Methods: Adults with normal EF and without structural heart disease undergoing echocardiography at a tertiary medical center with a repeat study ≥6 months from baseline were identified. Severe DD was defined by ≥3/4 abnormal DD parameters (medial e’, medial E/e’, tricuspid regurgitation velocity, left atrial volume index) and moderate DD by ≥2. Results: Among 30,428 patients (median age 60; 50% women), FTR was absent in 73%, mild in 22%, moderate in 4%, and severe in 0.4%. Severe DD was present in 2%, 5%, 11%, and 13% patients, respectively, (p<.001) and moderate DD in 9%, 19%, 31%, and 48%, respectively (p<.001). The association of DD with increasing FTR was independent of all clinical characteristics. Over median 3.0 (IQR 1.5-5.4) years, incident severe and moderate DD developed more frequently with increasing FTR severity ( Figure) . Findings were confirmed in a propensity-matched subset where patients were matched for age, sex, BMI, atrial fibrillation, and comorbidities and in patients without lung disease or ≥moderate right ventricular enlargement. Conclusions: Patients with FTR of undefined etiology commonly have DD suggesting the presence of underlying left heart disease. Patients without apparent DD or HF at baseline who have FTR remain at significantly increased risk of developing DD over follow-up and may be a target population for therapies to prevent progression to clinical HFpEF.

Abstract Background Atrial functional mitral regurgitation (AFMR) is an increasingly recognized cause of functional MR thought to result from left atrial enlargement and myopathy in the setting of preserved left ventricular geometry and function. AFMR mostly occurs in patients with atrial fibrillation (AF) and/or heart failure with preserved ejection fraction. Purpose We investigated whether the use of an artificial intelligence-based electrocardiogram (AI-ECG) can identify patients with new-onset AF and sinus rhythm (SR) who are at highest risk of developing AFMR. Methods Adults with a new diagnosis of AF between 2010 and 2021 who had a transthoracic echocardiogram (TTE) within 1 month after AF diagnosis were identified. Similarly, adults in SR who never had AF diagnosis and had a TTE during the same period were identified. Exclusion criteria from both groups included &gt;mild MR at baseline, primary mitral valve disease, cardiomyopathy, ≥moderate aortic valve disease, current or previous low ejection fraction, enlarged left ventricle, cardiac devices, previous cardiac surgeries, and the absence of follow-up TTE ≥6 months from baseline. Only patients who had ECG within 10 days of the TTE were included. When multiple ECGs were available, the closest was considered. A previously trained AI-ECG algorithm to detect the probability of AF was utilized. Incident AFMR was defined as &gt;mild functional MR in the absence of &gt;mild left ventricle enlargement or dysfunction. Diastolic dysfunction was defined according to ASE/EACVI guidelines. Results Overall, 1,570 patients with new-onset AF (median age 67 years; 34% females) and 16,802 patients in SR (median age 59 years; 46% females) were included. The median AI ECG probability for AF was 43% (IQR 26%-59%) in the new-onset AF group and 2% (0.5%-7%) in the SR group, Figure 1. Incident AFMR occurred in 152 patients in the AF group over median 3.06 (IQR 1.5-5.2) years of follow-up and in 482 patients in the SR group over median 3.0 (1.5-5.6) years of follow-up. The probability of silent AF by the AI-ECG was associated with incident AFMR in the new-onset AF group [hazard ratio 1.19 (95% CI 1.11-1.28) per 10%, p &lt;.001] and the SR group [hazard ratio 1.19 (95% CI 1.12-1.25) per 10%, p &lt;.001]. The AI ECG-derived AF probability remained as an independent risk factor for AFMR in multivariable analysis in both AF and SR, Table 1. Conclusion The AI ECG for AF might be able to reflect the degree of left atrial myopathy and thus the risk of incident AFMR in patients with AF and SR.Distribution of AI ECG probability of AFMultivariable risk factors for AFMR

Abstract Background Atrial fibrillation (AF) is associated with increased risk of incident tricuspid regurgitation (TR), but types of incident TR in AF versus sinus rhythm (SR) are not well-defined. Purpose We aimed to compare the risk of the different types of incident ≥moderate TR in AF and SR. Methods Adults first diagnosed with AF (2010-2021) who had a transthoracic echocardiogram (TTE) within 30 days after AF and adults with no diagnosis of AF who had a TTE in the same period were identified. Patients with previous cardiac surgeries, congenital heart disease, cardiomyopathy, cardiac devices, primary valve disease, previous or current ejection fraction (EF) &lt;50%, severe diastolic dysfunction (SDD), ≥moderate left-sided valve disease (LVD), right ventricular systolic pressure (RVSP) ≥50 mmHg, ≥moderate TR, any tricuspid stenosis, or with no follow-up TTE ≥6 months from baseline were excluded. Patients were followed for the development of ≥moderate TR, the type of which was identified in a hierarchal order: 1) pacemaker-associated TR, 2) LVD-associated TR in the setting of ≥moderate LVD, 3) low EF or SDD-related TR, 4) pulmonary hypertension (PH)-associated TR if RVSP was ≥50 mmHg, 5) other ventricular functional TR (VFTR) if there was &gt;mild RV enlargement or dysfunction, and 6) atrial functional TR (AFTR) when none of the previous was present. Patients were also followed for the occurrence of risk factors for TR (pacemaker insertion, ≥moderate LVD, low EF or SDD, PH, &gt;mild RV enlargement or dysfunction) in a hierarchal order, and both the prevalence and future risk of the corresponding type of ≥moderate TR was determined at the onset of these conditions in AF and SR. Results Overall, 1,360 patients with new-onset AF (median age 67 years, 34% females) and 20,438 patients in SR (median age 60 years; 54% females) were included. Over median 3.8 (IQR 1.8-6.6) years, incident ≥moderate TR occurred in 110 patients with new-onset AF [2.13 per 100-person years] compared to 378 patients in SR [0.41 per 100-person years, p &lt;.001]. All types of incident ≥moderate TR occurred more frequently in AF (p &lt;.001 for all). The distribution and incidence of each type of TR in AF and SR are shown in Figure 1. The incidence of risk factors associated with the development of TR was higher in the AF group, except for pre-capillary PH, Figure 2A. At time of diagnosis or occurrence of these conditions, the prevalence of the corresponding TR types was higher in AF, except for pacemaker-TR, Figure 2B. The incidence of the corresponding TR type after occurrence of TR risk factors was higher in the AF group for LVD-TR and low EF/SDD-associated TR (p ≤0.03); although numerically higher in AF, the association was only borderline for PH-TR (p =0.05), Figure 2C. Conclusion Incident ≥moderate TR of all types occurred more frequently in patients with AF vs. SR and the distribution of TR types differed by rhythm. Patients with AF may benefit from a closer follow-up.Distribution and incidence rates of TRIncidence of TR risk factors & TR after

Abstract Background Atrial fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF) are closely associated diseases that frequently coexist. However, due to the overlapping symptoms, the diagnosis of HFpEF can be overlooked with symptoms being attributed to AF. Purpose We aimed to investigate the prevalence of diastolic dysfunction (DD) in patients with new-onset AF compared to sinus rhythm (SR), study changes in diastolic function parameters over time in the two groups and compare the incidence of DD at follow-up. Methods Adults with new diagnosis of AF and adults in SR were identified. Patients with previous cardiac surgeries, congenital heart disease, hypertrophic or infiltrative cardiomyopathy, primary mitral disease, left-sided valve disease, low ejection fraction, enlarged left ventricle, or with no 6-month follow-up echocardiogram were excluded. Diastolic function was assessed through 4 components: mitral medial e’ &lt;0.07 m/sec, mitral medial E/e’ &gt;15 in SR and &gt;11 in AF, TR velocity &gt;2.80 m/sec, and left atrial volume index &gt;34 ml/m2, with severe DD (SDD) defined by ≥3/4 findings and moderate DD (MDD) by ≥2/4 abnormal diastolic function parameters. Annualized changes were calculated as the difference between follow-up and baseline values divided by years in between. In a secondary analysis, patients with new-onset AF were propensity score-matched to patients with SR in a 3:1 ratio based on age, sex, body mass index, and comorbidities. Results Overall, 1,747 patients with incident AF (median age 67 years; 34% females) and 29,623 in SR (median age 59 years; 51% females) were included. New-onset AF was independently associated with the presence of SDD vs SR (8% vs 2%) and MDD (25% vs 11%, p&lt;.001 for both in adjusted analysis). Over median follow-up of 3.2 (IQR 1.6-5.8) years, annualized severity progression in each of the 4 diastolic function parameters was greater in the AF group (p&lt;.001 for all), Table. The incidence rates of SDD and MDD were 3.7 and 8.8 per 100-person year, respectively, in AF versus 1.1 and 3.6 per 100-person years, respectively, in SR (p&lt;.001 for both at univariate and multivariable analysis), Figure. Results were similar in the propensity-score matched analysis. Conclusions Patients with new-onset AF more commonly have moderate or severe diastolic dysfunction that indicates the presence of potentially overlooked clinical HFpEF (when symptoms exist) or preclinical HFpEF (when symptoms are absent) compared to patients in SR. In long-term follow-up, patients with AF display accelerated progression in DD; suggesting that therapies to prevent progression to symptomatic HFpEF may be highest value in this patient population.

Abstract Background and Aims Atrial fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF) are intimately associated disorders; HFpEF may be overlooked in AF when symptoms are simply attributed to dysrhythmia, and incident AF may identify patients at risk for developing diastolic dysfunction (DD). This study aimed to investigate the prevalence and incidence of DD in patients with new-onset AF compared with sinus rhythm (SR). Methods Adults with new-onset AF (n = 1747) or SR (n = 29 623) and no structural heart disease were identified. Propensity score matching was performed (1:3 ratio) between AF and SR based on age, sex, body mass index, and comorbidities. Severe DD (SDD) was defined by ≥3/four abnormal parameters (medial e’, medial E/e’, tricuspid regurgitation velocity, and left atrial volume index) and ≥moderate DD (&gt;MDD) by ≥2/4. Annualized changes in DD indices were determined. Results New-onset AF was independently associated with SDD (8% vs. 3%) and ≥MDD (25% vs. 16%); 62% of patients with AF had high-risk H2FPEF scores, and 5% had clinically recognized HFpEF. Over a median follow-up of 3.2 (interquartile range 1.6–5.8) years, DD progressed two–four-fold more rapidly in those with new-onset AF (P &lt; .001 for all). The risk for incident DD was increased in new-onset AF [hazard ratio (95% confidence interval) 2.69 (2.19–3.32) for SDD and 1.73 (1.49–2.02) for ≥MDD]. Conclusions Patients with new-onset AF display high-risk features for HFpEF at diagnosis, emphasizing the importance of evaluating for HFpEF among symptomatic patients with AF. Patients with new-onset AF have accelerated progression in DD over time, which may identify patients with preclinical HFpEF, where preventive therapies may be tested.

Abstract Aims Atrial functional mitral regurgitation (AFMR) has been associated with atrial fibrillation (AF) and heart failure with preserved ejection fraction. However, data on incident AFMR are scarce. We aimed to study the incidence, risk factors, and clinical significance of AFMR in AF or sinus rhythm (SR). Methods and results Adults with new diagnosis of AF and adults in SR were identified. Patients with &gt;mild MR at baseline, primary mitral disease, cardiomyopathy, left-sided valve disease, previous cardiac surgery, or with no follow-up echocardiogram were excluded. Diastolic dysfunction (DD) was indicated by ≥2/4 abnormal diastolic function parameters [mitral medial e′, mitral medial E/e′, tricuspid regurgitation velocity, left atrial volume index (LAVI)]. Overall, 1747 patients with AF and 29 623 in SR were included. Incidence rate of &gt;mild AFMR was 2.6 per 100 person-year in new-onset AF and 0.7 per 100 person-year in SR, P &lt; 0.001. AF remained associated with AFMR in a propensity score-matched analysis based on age, sex, and comorbidities between AF and SR [hazard ratio: 3.80 (95% confidence interval 3.04–4.76)]. Independent risk factors associated with incident AFMR were age ≥65 years, female sex, LAVI, and DD in both AF and SR, in addition to rate (vs. rhythm) control in AF. Incident AFMR was independently associated with all-cause death in both groups (both P &lt; 0.001). Conclusions AF conferred a three-fold increase in the risk of incident AFMR. DD, older age, left atrial size, and female sex were independent risk factors in both SR and AF, while rhythm control was protective. AFMR was universally associated with worse mortality.