Tachycardia-induced Cardiomyopathy Research Articles

Outcome after cryoballoon ablation of persistent atrial fibrillation in patients with heart failure with preserved ejection fraction versus tachycardiomyopathy: a propensity score-matched analysis

Abstract Introduction Atrial fibrillation (AF) often coexists with heart failure (HF). The aim of the study was to detect differences in outcome between patients with arrhythmia induced cardiomyopathy (AIC)/tachycardiomyopathy and HFpEF undergoing cryoballoon pulmonary vein isolation (cryo-PVI) using a propensity score-based model. Methods In this retrospective observational study, we analysed persistent AF patients with HFpEF and AIC undergoing cryoballoon ablation between 2014 and 2020. AIC was diagnosed ex juvantibus during the first year after ablation at the 3- and 12-month follow-up when LVEF recovered to > 50% and by more than 10% after ablation and a different aetiology for reduced LVEF was excluded. Propensity score matching was used to pair patients based on their age, sex, CHA2DS2-VASc score and left atrial (LA) area. The primary endpoint was the first documented > 30-s recurrence of atrial arrhythmia after a 3-month blanking period during the one-year follow-up. The secondary endpoints were improvements in NYHA class and reduction of LA area. For identification of independent predictors of atrial arrhythmia recurrence after ablation, univariate and multivariate Cox regression analyses were performed. Results Out of 1293 consecutive patients who underwent cryo-PVI, 148 persistent AF patients with HFpEF and 66 patients with AIC were identified. Propensity score matching yielded 46 patients in each group. HFpEF patients were more symptomatic than AIC patients (NYHA: 2.4 +/- 0.5 vs. 2.0 +/- 0,8; p = 0.002). Other baseline characteristics did not differ between the two groups, except LVEF (57 % [IQR: 52-62%] vs. 41% [QR: 35%-45%]; p= 0.002). Kaplan-Meier curves (Figure 1) demonstrated no difference in recurrence-free survival rate between the groups during the 12-month follow-up (71.7 % vs. 56.5%, log-rank P = 0.16). After the 12-month follow-up, the median LA area decreased significantly in the HFpEF group from 25.8 cm2 (IQR: 23.4-29.5 cm2) to 24.6cm2 (IQR: 22.0-29.6 cm2; p = 0.045) and in the AIC group from 26.6 cm2 (IQR: 22.9-31.1 cm2) to 23.0 cm2 (IQR: 18.3-25.2 cm2; p=0.024). At the 12-month follow-up the median LA-area was significantly higher in the HFpEF than in the AIC cohort (p= 0.007). NYHA class improved significantly in both groups from baseline. At the 1-year follow-up NYHA class was similar between both groups (1.6 +/- 0.8 vs. 1.4 +/- 0,6; p = 0.206). After univariate and multivariate analysis, the following predictors of atrial arrhythmia recurrence were identified: body-mass-index (BMI; HR = 1.082, p = 0.015) and LA area (HR = 1.079, p = 0.003). Conclusions Cryoballoon catheter ablation of persistent AF seems to have similar effectiveness on arrhythmia free survival in patients with HFpEF and AIC. NYHA class and LA enlargement improved after ablation in both groups although LA area in HFpEF was higher than in AIC patients at follow-up. BMI and LA area were identified as predictors of arrhythmia recurrence.

Definition and management of arrhythmia-induced cardiomyopathy: findings from the EHRA SIC survey

Abstract Background Arrhythmia-induced Cardiomyopathy (AiCM) represents a subtype of heart failure (HF) in the context of a sustained arrhythmia. However, clear definitions and management recommendations for AiCM are lacking. Purpose The European Heart Rhythm Association Scientific Initiatives Committee (EHRA SIC) conducted a survey to determine the current definitions and management of patients with AiCM among European and non-European electrophysiologists. Methods A 25-item online questionnaire was developed and distributed among EP research network centres between September 4th and October 5th 2022. Results Out of the 206 respondents, 16% were females and the most (33%) were between 40-49 years old. Most of the respondents were EP-Specialists (81%) working at a University Hospital (47%). While most participants (67%) agreed that AiCM should be defined as a left ventricular ejection fraction (LVEF) impairment after new onset of an arrhythmia and/or LVEF recovery after treatment of the culprit arrhythmia, only 35% identified a specific LVEF drop/improvement to diagnose AiCM, the majority (50%) agreeing with a 10% change in LVEF (Figure) but with the rest of the experts choosing a wide range of values (from 5 to 20% LVEF drop). Most respondents used all available therapies in AiCM patients: catheter ablation was chosen by 93%, electrical cardioversion by 83%, antiarrhythmic drugs by 76% and adjuvant HF treatment were used by 76%. 83% of respondents indicated that adjuvant HF treatment should be started at first diagnosis of HF prior to antiarrhythmic treatment and 84% agreed that the therapy should be stopped within six months after LVEF normalization. Responses for the optimal time point for the first reassessment of LVEF during FU varied markedly (1 day to over 6 months after antiarrhythmic treatment). Conclusion This EHRA Survey reveals varying practices in defining and managing AiCM among European and non-European physicians. There is an unmet need for a consensus in the definition and management of AiCM patients to improve patient care.Figure

Newly diagnosed heart failure in patients with atrial fibrillation referred for catheter ablation - identifying patients with arrhythmia-induced cardiomyopathy

Abstract Introduction Atrial tachyarrhythmias are primary drivers in the development of arrhythmia-induced cardiomyopathy (AiCM). The restoration of sinus rhythm in patients with an AF (atrial fibrillation) based AiCM results in enhancement of left ventricular ejection fraction (LV-EF). This study aims to assess the prevalence of undiagnosed and unexplained heart failure among patients with AF referred for catheter ablation and seeks to phenotype these patients. Methods Our registry, a prospective, observational clinical cohort that recruits patients with heart rhythm disorders at a large tertiary-care center since March 2021 was interrogated for AF patients. These patients underwent screening for heart failure based on clinical, laboratory, and imaging characteristics. Undiagnosed heart failure at baseline, lack of heart failure medication and absence of known structural heart disease were considered suspicious for AiCM. Results A total of 1225 patients were analyzed. 35.2% were female, median age 67 (IQR 59;75) years, median LV-EF 55.0 (IQR 50;60) % and median N-terminal pro B-type natriuretic peptide (NT-proBNP) 686 (IQR 210;1630) mg/dl. NYHA class I was reported in 28.3% cases, NYHA class II in 32.2%, NYHA class III in 20.2% and NYHA class IV in 2%. At baseline, 263 patients (17.6%) had an LV-EF < 50% of those 110/263 (42%) with suspected AiCM. Patients with suspected AiCM were 67 (IQR 58;76) years old, 40.9% were female, median LV-EF was 41.0 (IQR 35;41) % and NT-proBNP at admission was 1681 (IQR 775;2352) mg/dl. Patients with suspected AiCM had a significantly reduced TAPSE (19 vs. 22 mm; p<0.001), showed generic characteristics of heart failure (NTproBNP: p<0.001, NYHA class: p=0.049), while EHRA score was significantly lower (p=0.006). In contrast, patients with known cardiomyopathy of non-AiCM origin at baseline and EF < 50% (n=153) had significantly higher LAVI (44.8 vs. 38.8 ml/m2; p=0.002), were predominantly male (76.5 vs. 59.1 %; p=0.004) and had lower GFR (60.2 vs. 68.5 ml/min; p=0.002) compared to AiCM patients. Among 29/110 suspected AiCM patients with available TTE at follow-up (within 12 months post-catheter ablation), 26/29 exhibited an improved LV-EF (40% at baseline vs. 54% at FU; p<0.001). 3/3 patients without LV-EF improvement exhibited arrhythmia recurrence. Conclusion Primary AiCM was suspected in 42% of all AF patients with reduced LV function referred for catheter ablation. These patients exhibited a different phenotype compared to the remaining cohort. After catheter ablation, ejection fraction improved in 90% of AiCM patients. These findings call for structured HF screening in clinical routine in AF patients. In the future, validated scores are required to enable early rhythm control for these patients.Proportion of patients with HFrEFCourse of EF after catheter ablation

Arrhythmia-induced versus arrhythmia-superimposed cardiomyopathy: outcome in patients with atrial fibrillation and heart failure undergoing cryoballoon pulmonary vein isolation

Abstract Introduction The outcome in patients with arrhythmia-induced cardiomyopathy (AIC) compared with that in patients with arrhythmia-mediated/superimposed cardiomyopathy (AMC) undergoing cryoballoon pulmonary vein isolation (cryo-PVI) is also poorly defined. Methods In this retrospective observational study, we analysed patients with AF and reduced left ventricular ejection fraction (LVEF < 50%) who underwent cryoballoon ablation between 2014 and 2020. Patients with LVSD were divided into AIC and AMC. AIC was diagnosed ex juvantibus during first year after ablation at 3- and 12-month follow-up when LVEF recovered to > 50% and by more than 10% after ablation and a different aetiology for reduced LVEF was excluded. AMC was diagnosed when structural heart disease was responsible for LVSD and AF had likely exacerbated pre-existing LVSD. For identification of independent predictors of LVEF non-improvement after ablation, univariate and multivariate logistic regression analyses were performed. LVEF non-improvement was defined when LVEF neither increased by more than 10% nor increased over absolute 50% at 12-month follow-up. The first documented > 30-s atrial arrhythmia recurrence after a 3-month blanking period during the one-year follow-up was compared by Kaplan-Meier analysis. Results Out of 1293 consecutive patients who underwent cryoballoon ablation, 113 AF patients with reduced LVEF (<50%) were identified. After 1-year follow-up these patients were divided into AIC (N= 77) and AMC (N = 36) groups. The prevalence of persistent AF was comparable in both groups (85.7% vs. 77.8 %, p = 0.435). LVEF, left atrial (LA) enlargement, and left ventricular end diastolic diameter (LVEDD) were similar between the groups. After one year, the median LVEF improved significantly in the AIC group from 42% (IQR: 35-45%) to 60% (IQR: 58-63%; p < 0.0001) and in the AMC group from 42% (IQR: 33-45%) to 47.5% (IQR= 43-53%; p=0.015). At follow-up LVEF was significantly higher in the AIC than in the AMC cohort (p < 0,001). After univariate and multivariate analysis, the following parameters were associated with non-LVEF improvement: LVEDD (OR = 1.12, p = 0.012) and atrial arrhythmia recurrence (OR = 5.87, p = 0.031; Figure 1). In the AIC group LA area decreased from 25.6 cm2 (IQR: 22.4-29.5 cm2) to 21.8 cm2 (IQR: 18.3-25.2 cm2; p = 0.012). In AMC patients LA enlargement did not change with respect to baseline. Kaplan-Meier curves demonstrated no difference in recurrence-free survival rate between the groups during the 12-month follow-up (75.3% vs. 75%, log-rank P = 0.89; Figure 2). Conclusions LVEDD and arrhythmia recurrence were identified as predictors of non-LVEF improvement after cryo-PVI. The LVEF increased in both groups after ablation, but in AIC group more than in AMC group. In the AIC group LA atrial area decreased compared to the AMC group. Atrial arrhythmia recurrence rates were comparable between AIC and AMC groups after 12 months.Figure 1Figure 2

Transient Left Ventricular Dysfunction from Cardiomyopathies to Myocardial Viability: When and Why Cardiac Function Recovers.

Transient left ventricular dysfunction (TLVD), a temporary condition marked by reversible impairment of ventricular function, remains an underdiagnosed yet significant contributor to morbidity and mortality in clinical practice. Unlike the well-explored atherosclerotic disease of the epicardial coronary arteries, the diverse etiologies of TLVD require greater attention for proper diagnosis and management. The spectrum of disorders associated with TLVD includes stress-induced cardiomyopathy, central nervous system injuries, histaminergic syndromes, various inflammatory diseases, pregnancy-related conditions, and genetically determined syndromes. Furthermore, myocardial infarction with non-obstructive coronary arteries (MINOCA) origins such as coronary artery spasm, coronary thromboembolism, and spontaneous coronary artery dissection (SCAD) may also manifest as TLVD, eventually showing recovery. This review highlights the range of ischemic and non-ischemic clinical situations that lead to TLVD, gathering conditions like Tako-Tsubo Syndrome (TTS), Kounis syndrome (KS), Myocarditis, Peripartum Cardiomyopathy (PPCM), and Tachycardia-induced cardiomyopathy (TIC). Differentiation amongst these causes is crucial, as they involve distinct clinical, instrumental, and genetic predictors that bode different outcomes and recovery potential for left ventricular function. The purpose of this review is to improve everyday clinical approaches to treating these diseases by providing an extensive survey of conditions linked with TLVD and the elements impacting prognosis and outcomes.

Definition and management of arrhythmia-induced cardiomyopathy: findings from the European Heart Rhythm Association survey.

Arrhythmia-induced cardiomyopathy (AiCM) represents a subtype of acute heart failure (HF) in the context of sustained arrhythmia. Clear definitions and management recommendations for AiCM are lacking. The European Heart Rhythm Association Scientific Initiatives Committee (EHRA SIC) conducted a survey to explore the current definitions and management of patients with AiCM among European and non-European electrophysiologists. A 25-item online questionnaire was developed and distributed among EP specialists on the EHRA SIC website and on social media between 4 September and 5 October 2023. Of the 206 respondents, 16% were female and 61% were between 30 and 49 years old. Most of the respondents were EP specialists (81%) working at university hospitals (47%). While most participants (67%) agreed that AiCM should be defined as a left ventricular ejection fraction (LVEF) impairment after new onset of an arrhythmia, only 35% identified a specific LVEF drop to diagnose AiCM with a wide range of values (5-20% LVEF drop). Most respondents considered all available therapies: catheter ablation (93%), electrical cardioversion (83%), antiarrhythmic drugs (76%), and adjuvant HF treatment (76%). A total of 83% of respondents indicated that adjuvant HF treatment should be started at first HF diagnosis prior to antiarrhythmic treatment, and 84% agreed it should be stopped within six months after LVEF normalization. Responses for the optimal time point for the first LVEF reassessment during follow-up varied markedly (1 day-6 months after antiarrhythmic treatment). This EHRA Survey reveals varying practices regarding AiCM among physicians, highlighting a lack of consensus and heterogenous care of these patients.

Predictors of systolic function recovery after atrial fibrillation ablation in heart failure patients

Introduction and objectivesAtrial fibrillation (AF) and heart failure (HF) often coexist. AF catheter ablation improves left ventricular ejection fraction (LVEF), but its impact varies between patients. We aimed to identify predictors of LVEF improvement in HF patients with impaired LVEF undergoing AF ablation. MethodsWe conducted a retrospective single-center study in HF patients with LVEF <50% undergoing AF catheter ablation between May 2016 and May 2022. The primary endpoint was the LVEF recovery rate (‘responders’). Secondary endpoints were one-year safety and effectiveness. We also aimed to validate a prediction model for LVEF recovery. ResultsThe study included 100 patients (79% male, median age 60 years, 70% with probable tachycardia-induced cardiomyopathy [TIC], mean LVEF 37%, 29% with paroxysmal AF). After a median follow-up of 12 months after catheter ablation, LVEF improved significantly (36±10% vs. 53±10%, p<0.001), with an 82% responder rate. A suspected diagnosis of TIC (OR 4.916 [95% CI 1.166–20.732], p=0.030), shorter QRS duration (OR 0.969 [95% CI 0.945–0.994], p=0.015), and smaller left ventricle (OR 0.893 [95% CI 0.799–0.999], p=0.049) were independently associated with LVEF improvement. Freedom from any documented atrial arrhythmia was 86% (64% under antiarrhythmic drugs), and the rate of adverse events was 2%. The prediction model had a good discriminative performance (AUC 0.814 [95% CI 0.681–0.947]). ConclusionIn AF patients with HF and impaired LVEF, suspected TIC, shorter QRS duration, and smaller LV diameter were associated with LVEF recovery following AF catheter ablation.

Predicting factors for omitting beta-blockers in patients with tachycardia-induced cardiomyopathy after successful catheter ablation for atrial fibrillation.

Tachycardia induces a reduction in the left ventricular ejection fraction (LVEF), which is defined as tachycardia-induced cardiomyopathy (TIC). Conversion to and maintenance of sinus rhythm by catheter ablation can improve LVEF in patients with TIC due to atrial fibrillation (AF). Beta-blockers are mandatory for the treatment of heart failure with reduced LVEF(HFrEF), but the necessity of beta-blockers in TIC patients even after catheter ablation remains unclear. We examined the effect of beta-blockers on cardiac function in TIC patients after catheter ablation. We retrospectively analyzed 124 patients with a history of heart failure and an LVEF of ≤ 50% who underwent catheter ablation for AF. TIC was defined as a ≥ 10% improvement in the baseline LVEF and an improvement to an LVEF of ≥ 50% at 6months after ablation. Patients with other cardiomyopathy diagnosed before the ablation were excluded. LVEF was significantly increased with the reductions of the left ventricular and left atrial volumes at the 6-month follow-up in all 80 patients with TIC. No beta-blockers were prescribed during the post-ablation follow-up in 21 patients with TIC. The absolute values of and changes in the echocardiographic parameters between before and after ablation were not significantly different between patients with and without beta-blockers after the ablation. A simple score using the history of hospitalization for heart failure and use of beta-blockers or diuretics prior to ablation was useful in identifying TIC patients who did not need prescription of beta-blockers after catheter ablation. LVEF similarly improved in both patients with and without prescription of beta-blockers after the ablation. Beta-blockers may not need to be prescribed after successful catheter ablation for AF in LVEF of ≤ 50% patients without other cause of cardiomyopathy diagnosed before the ablation, a history of hospitalization for heart failure and prescription of beta-blockers and diuretics before the ablation.

Time to Recovery from Systolic Dysfunction Correlates with Left Ventricular Fibrosis in Arrhythmia-Induced Cardiomyopathy.

Arrhythmia-induced cardiomyopathy (AIC) is characterized by the reversibility of left ventricular (LV) systolic dysfunction (LVSD) after rhythm restoration. This study is a cardiac magnetic resonance tomography substudy of our AIC trial with the purpose to investigate whether left ventricular fibrosis affects the time to recovery (TTR) in patients with AIC. Patients with newly diagnosed and otherwise unexplainable LVSD and tachyarrhythmia were prospectively recruited. LV ejection fraction (LVEF) was measured by echocardiography at baseline and 2, 4, and 6 months after rhythm control, and stress markers were assessed. After initial rhythm control, LV fibrosis was assessed through late gadolinium enhancement (LGE). Patients were diagnosed with AIC if their LVEF improved by ≥15% (or ≥10% when LVEF reached ≥50%). Non-responders served as controls (non-AIC). The LGE analysis included 39 patients, 31 of whom recovered (AIC). LV end-systolic diameters decreased and LVEF increased during follow-up. LV LGE content correlated positively with TTR (r = 0.63, p = 0.003), with less LGE favoring faster recovery, and negatively with ΔLVEF (i.e., LVEF at month 2 compared to baseline) as a marker of fast recovery (r = -0.55, p = 0.012), suggesting that LV fibrosis affects the speed of recovery. LV fibrosis correlated positively with the time to recovery in patients with AIC. This correlation may help in the estimation of the recovery period and in the optimization of diagnostic and therapeutic strategies for patients with AIC.

Clinical Characterization of Arrhythmia-Induced Cardiomyopathy in Patients With Tachyarrhythmia and Idiopathic Heart Failure

BackgroundArrhythmia-induced cardiomyopathy (AIC) is a known entity, but prospective evidence for its characterization is limited. ObjectivesThis study aimed to: 1) determine the relative frequency of the pure form of AIC in the clinically relevant cohort of patients with newly diagnosed, otherwise unexplained left ventricular systolic dysfunction (LVSD) and tachyarrhythmia; 2) assess the time to recovery from LVSD; and 3) identify parameters for an early diagnosis of AIC. MethodsPatients were prospectively included, underwent effective rhythm restoration, and were followed-up at 2, 4, and 6 months to evaluate clinical characteristics, biomarkers, and cardiac imaging including cardiac magnetic resonance imaging. Patients with recurred arrhythmia were excluded from analysis. Results41 of 50 patients were diagnosed with AIC 6 months after rhythm restoration. Left ventricular (LV) ejection fraction increased 2 months after rhythm restoration from 35.4% ± 8.2% to 52.7% ± 8.0% in AIC patients vs 37.0% ± 9.5% to 43.3% ± 7.0% in non-AIC patients. From month 2 to 6, LV ejection fraction continued to increase in AIC patients (57.2% ± 6.1%; P < 0.001) but remained stable in non-AIC patients (44.0% ± 7.8%; P = 0.628). Multivariable logistic regression analysis revealed that lower LV end-diastolic diameter at baseline could be used for early diagnosis of AIC, whereas biomarkers and other morphological or functional parameters, including late LV gadolinium enhancement, did not show suitability for early diagnosis. ConclusionsWe observed a high prevalence of AIC in patients with otherwise unexplained LVSD and concomitant tachyarrhythmia, suggesting that this condition may be underdiagnosed in clinical practice. Most patients recovered fast, within months, from LVSD. A low initial LV end-diastolic diameter may constitute an early marker for diagnosis of AIC.

Clinical Features of Tachycardia-induced Cardiomyopathy in Patients with Atrial Fibrillation.

Objective Atrial fibrillation (AF) is the most common cause of tachycardia-induced cardiomyopathy (TIC). However, which patients with AF are prone to developing TIC remains unclear. In this study, we investigated the clinical features of AF patients with TIC. Methods This single-center study included 722 patients with AF (average age, 63.1±10.2 years old; 191 women) who underwent radiofrequency catheter ablation. We defined TIC as an initial left ventricular ejection fraction (LVEF) of <40% and a >20% recovery of the LVEF after successful AF ablation and compared the clinical characteristics between the TIC and control groups. Results The proportions of type 2 diabetes (30.5% vs. 14.7%), renal dysfunction (34.2% vs. 23.8%), hypertension (67.1% vs. 54.8%), and persistent AF (62.2% vs. 32.2%) were significantly higher in the TIC group (n=82) than in the control group (n=640). The atrioventricular nodal effective refractory period (AVNERP) (303±72 ms vs. 332±86 ms; p=0.017) was significantly shorter in the TIC group than in the control group. A multivariable analysis found that persistent AF [odds ratio (OR), 3.19; 95% confidence interval (CI), 1.94-5.24], renal dysfunction (OR, 1.87; 95% CI, 1.06-3.32), and type 2 diabetes (OR, 2.30; 95% CI, 1.31-4.05) were significantly associated with TIC. Conclusion Comorbid renal dysfunction and type 2 diabetes were clinical features of AF patients with TIC. Persistent AF, and short AVNERP may be involved in the development of TIC.

Cryoballoon ablation for pulmonary vein isolation in the treatment of chronic heart failure with reduced left ventricular ejection fraction following tachycardia-induced cardiomyopathy

Cryoballoon ablation for pulmonary vein isolation in the treatment of chronic heart failure with reduced left ventricular ejection fraction following tachycardia-induced cardiomyopathy

Severity of Left Ventricular Dysfunction in Patients With Tachycardia-Induced Cardiomyopathy: Impacts on Remodeling After Atrial Flutter Ablation

Tachycardia-induced cardiomyopathy is defined as a reversible left ventricular (LV) systolic dysfunction (SeD) resulting from a sustained fast heart rate. LV remodeling in patients with severe LV dysfunction at diagnosis remains poorly understood. In this retrospective cohort study, we described LV remodeling in 50 patients who underwent atrial flutter ablation. These patients were divided into severe LV SeD (LV ejection fraction [EF] ≤30%) and LV nonsevere SeD (LVEF 31% to 50%) at baseline. All continuous variables are expressed as median and interquartile range. LVEF was 18% (13 to 25) and 38% (34 to 41) in the SeD (n=29) and LV nonsevere SeD (n=21) groups, respectively. At baseline, patients with SeD had higher LV end-diastolic diameter (56 [54 to 59] vs 49mm [47 to 52], p<0.01), LV end-systolic diameter (48 [43 to 51] vs 36mm [34 to 41], p<0.01), LV end-diastolic volume (71 [64 to 85] vs 56ml/m2 [46 to 68], p<0.01), LV end-systolic volume (56 [53 to 70] vs 36ml/m2 [27 to 42], p<0.01), and lower tricuspid annular plane systolic excursion (12 [10 to 13] vs 16mm [13 to 19], p<0.01). At last follow-up, LVEF was not statistically significantly different between groups. However, LV end-systolic diameter (36 [34 to 39] vs 32mm [32 to 34], p=0.01) and LV end-systolic volume (29 [26 to 35] vs 25ml/m2 [20 to 29], p=0.02) remained larger in the SeD group. Seven patients (14%), all from the SeD group, had a LVEF ≤35% 2months after rhythm control, and reverse remodeling was observed up to 9months. In conclusion, more than half of patients with tachycardia-induced cardiomyopathy and atrial flutter had LVEF ≤30% at baseline. LVEF recovery and LV remodeling were observed beyond 2months, highlighting the importance of rhythm control and early guideline-directed medical therapy in these patients.

Tachycardia-induced metabolic rewiring as a driver of contractile dysfunction.

Prolonged tachycardia-a risk factor for cardiovascular morbidity and mortality-can induce cardiomyopathy in the absence of structural disease in the heart. Here, by leveraging human patient data, a canine model of tachycardia and engineered heart tissue generated from human induced pluripotent stem cells, we show that metabolic rewiring during tachycardia drives contractile dysfunction by promoting tissue hypoxia, elevated glucose utilization and the suppression of oxidative phosphorylation. Mechanistically, a metabolic shift towards anaerobic glycolysis disrupts the redox balance of nicotinamide adenine dinucleotide (NAD), resulting in increased global protein acetylation (and in particular the acetylation of sarcoplasmic/endoplasmic reticulum Ca2+-ATPase), a molecular signature of heart failure. Restoration of NAD redox by NAD+ supplementation reduced sarcoplasmic/endoplasmic reticulum Ca2+-ATPase acetylation and accelerated the functional recovery of the engineered heart tissue after tachycardia. Understanding how metabolic rewiring drives tachycardia-induced cardiomyopathy opens up opportunities for therapeutic intervention.

Left ventricular fibrosis influences the time to recovery in patients with arrhythmia-induced cardiomyopathy

Abstract Background The hallmark of arrhythmia-induced cardiomyopathy (AIC) is reversibility of left ventricular systolic dysfunction (LVSD) following rhythm restoration. Atrial fibrillation and LVSD very frequently co-exist and hence AIC is likely to be under recognized in daily practice. We tested the hypothesis, that left ventricular fibrosis has an influence on the time to recovery (TTR) in patients with AIC. Method We prospectively screened patients hospitalized for newly diagnosed and otherwise unexplainable LVSD (i.e. left ventricular ejection fraction (LVEF) &amp;lt;50%) and coexisting tachyarrhythmia (atrial fibrillation/flutter + heart rate (HR) &amp;gt;100/min). Causes other than tachyarrhythmic for LVSD had to be excluded (e.g. valvular, ischaemic, inflammatory). Left ventricular function was assessed by echocardiography at presentation and at follow-up visits 2, 4, and 6 months after rhythm control. Left ventricular (LV) late gadolinium enhancement (LGE) was measured via magnetic resonance imaging after rhythm restoration. Patients were classified AIC, if LVEF significantly recovered after 6 months (increase by ≥15% or above 50% with an increase of ≥10%) and then correlated with LGE as an indicator for fibrosis. Results 39 patients were included in the LGE analysis, 31 of them recovered and were classified AIC. Although we found no difference in LGE content in AIC vs. non-AIC patients (mean ± SEM 7.7 ± 0.9% vs. 6.5 ± 1.4%; p = 0.542) and contingency analysis of AIC/non-AIC vs. LGE-positive/LGE-negative patients revealed no difference between the groups (p = 0.682), there was a negative correlation of ΔLVEF (month 2 minus baseline) with LGE (Fig. 1) and a positive correlation of the TTR with LGE (Fig. 2) in LGE-positive patients, suggesting an influence of LV fibrosis on the speed of recovery. Conclusion Reliable criteria for recovery of LVEF in patients with newly diagnosed LVSD and coexisting arrhythmia are lacking. We found, that LV LGE correlated with the time to recovery of LVEF in patients with AIC. These results may help to estimate the recovery period and thereby optimize the diagnostic and therapeutic strategy for patients with AIC.Figures 1 and 2.

Impact of pharmacological treatment for heart failure after myocardial recovery in arrhythmia-induced cardiomyopathy

Abstract Introduction There is scarce evidence regarding the optimal medical treatment of patients with heart failure and recovered LVEF. To date, no study has analyzed the efficacy of maintaining neurohormonal blockade in patients with arrhythmia-induced cardiomyopathy (AiCM) after LVEF normalization. Purpose The aim of this study is to analyze impact of pharmacological treatment for heart failure in preventing heart failure relapse after myocardial recovery in AiCM. Methods We analyze data from a single-center cohort of 200 patients admitted for heart failure and ventricular dysfunction initially attributed to AiCM between 2008 and 2020. Myocardial recovery was defined as an improvement in LVEF up to &amp;gt; = 50% (complete recovery) or an increase of &amp;gt; = 10% up to a value of LVEF &amp;gt;= 40% (partial recovery). Heart failure relapse was defined as a decrease in LVEF to &amp;lt;50% in those with previous complete recovery or a decrease of &amp;gt; = 10% in patients with partial recovery, unplanned Emergency Department (ED) visit or hospital admission for heart failure. As drug prescriptions are not constant over follow up, changes in medication have been recorded and time varying covariates were used for statistical analysis. A Fine and Gray competing-risk multivariate regression was performed, adjusting for initial LVEF at admission, degree of myocardial recovery (complete or partial), presence of underlying cardiomyopathy and age, considering death as competing risk. Results Over a median of 6.14 years, most of the patients had a complete myocardial recovery (n = 164; 82.0%). 24 patients (12%) had partial recovery and 12 patients (6.0%) did not show significant improvement in ventricular function. At the moment of myocardial recovery, ACEI/ARB/ARNI were prescribed in 160 patients (85.11%); beta-blockers in 170 (90.43%); ARB in 112 (59.57%); iSGLT2 in 8 (4.26%); antiarrhythmic drugs in 75 (39.89%) and Digoxin in 40 (21.28). From 188 patients with initial LVEF recovery, 64 (34.04%) had a relapse of systolic dysfunction. 65 patients (34.57%) required unplanned Emergency Department (ED) visits and 40 patients (21.28%) needed hospital admission for heart failure. Maintenance of ACEI/ARB/ARNI and beta-blockers after myocardial recovery was associated with a significant lower risk of HF relapse [sHR 0.43 (95% CI 0.26 - 0.73), p 0.002 for ACEI/ARB/ARNI]; [sHR 0.52 (95% CI 0.29 - 0.92), p 0.025 for beta-blockers]. ARM was associated with a non-significant lower risk of HF relapse [sHR 0.67 (95% CI 0.42 - 1.09), p 0.093]. Treatment with antiarrhythmic drugs [sHR 0.90 (95% CI 0.54 - 1.51), p 0.696] and Digoxin [sHR 0.90 (95% CI 0.54 - 1.51), p 0.696] did not show benefit in this study. Conclusions Maintenance of ACEI/ARB/ARNI and beta-blockers after myocardial recovery was associated with a significant lower risk of HF relapse after myocardial recovery in patients with AiCM.Risk of HF relapse - ACEI ARB ARNIRisk of HF relapse - BetaBlockers

Long-term outcomes of patients with tachycardia-induced cardiomyopathy

Abstract Introduction Tachycardia-induced cardiomyopathy (TCM) is a reversible type of heart failure that occurs after sustained tachyarrhythmia. TCM can occur on its own (pure TCM) or superimposed on another type of CM (impure TCM). Survival data for such patients are lacking. Purpose We aimed to compare the 5-year survival rates of pure and impure TCM patients compared to other types of CM. Methods We retrospectively identified patients with reduced ejection fraction (≤50%) and/or atrial fibrillation or flutter with a left ventricular ejection fraction (LVEF) that improved from baseline (≥ 15% in LVEF at follow-up (FU)) through retrospective chart review. Patients were then divided into four groups (pure TCM, impure TCM, ischemic CM and nonischemic CM). The primary outcome was defined as a composite of death, life-threatening arrhythmia or cardiogenic shock. Secondary outcome was cardiovascular re-admission during FU. Results 238 patients were included (mean age 68 ± 12 years, 31% women). Patients were classified as pure TCM in 35%, impure TCM in 18%, ischemic CM in 24% and non-ischemic CM in 23%. Median FU was 5 (IQR 4-6) years. 13 (5.5%) patients reached the composite outcome at FU. While patients with pure TCM showed similar survival rates as patients with ischemic or nonischemic CM (Figure), a significant difference in survival was observed between impure CM and ischemic and non-ischemic CM with respect to the composite outcome (11% vs 2.7%, p = 0.024). Patients with impure CM showed comparable rates of cardiovascular re-admission during FU compared to patients with ischemic and non-ischemic CM (45% vs. 49%, p = 0.91). Conclusions TCM patients have survival rates similar to patients with another type of CM. Patients with TCM on top of a non-ischemic or ischemic CM (impure TCM) demonstrated the lowest 5-year survival rates. Early detection and treatment of cardiac arrhythmias in patients with impure TCM seem to be warranted.Figure

Treatment with catheter ablation for patients with arrhythmia-induced cardiomyopathy caused by atrial fibrillation promises a good prognosis.

Clinical outcomes after catheter ablation in patients with reduced left ventricular (LV) ejection fraction (EF) and atrial fibrillation (AF) remain unclear. This study aimed to explore the clinical outcomes of patients with arrhythmia-induced cardiomyopathy (AIC) and the influence of pharmacological treatment on clinical outcomes in patients with AIC after the procedure. Ninety-six patients with AF with a reduced LVEF (LVEF < 50%, 66.7 ± 10.9years; 72 males) underwent AF ablation. AIC was defined as patients whose LVEF recovered ≥ 50% after catheter ablation (n = 67) and patients whose LVEF remained reduced were defined as non-AIC (n = 29). During a median follow-up of 25 (13-40) months, Kaplan-Meier analysis demonstrated that patients with AIC were associated with less frequent cardiovascular death (p = 0.025) and hospitalization for worsening heart failure (p < 0.001) than those without AIC. Freedom from AF recurrence was similar between the two groups (p = 0.47). In multivariate analysis, the LV end-diastolic diameter (p = 0.0002) and the CHA2DS2-VASc scores (p = 0.0062) were independent predictors of AIC. Among the 67 patients with AIC, no significant differences in baseline characteristics, except for LV chamber size and cryoballoon use, were observed between patients with AIC with (n = 31) and without renin-angiotensin system (RAS) inhibitors (n = 36). In the Kaplan-Meier analysis, cardiovascular death, hospitalization for worsening heart failure, and AF recurrence after catheter ablation did not differ between patients treated with and without RAS inhibitors (all p > 0.05). Catheter ablation in patients with AIC due to AF is associated with a good post-procedural prognosis.IRB information The study was approved by the Research Ethics Committee of the University of Fukui (No. 20220151) and clinical trial registration (UMIN000050391).

Benefit of Catheter Ablation for Atrial Fibrillation in Heart Failure Patients with Different Etiologies.

(1) Background: A plethora of studies have elucidated the safety and efficacy of catheter ablation (CA) for patients afflicted with atrial fibrillation (AF) and concomitant reduction in left ventricular ejection fraction (LVEF). Nevertheless, the literature on the benefits of CA in the specific etiological context of heart failure (HF) remains limited. This study delineates a comparative assessment of outcomes for patients with AF and reduced LVEF across the primary etiologies. (2) Methods: Our inquiry encompassed 216 patients diagnosed with congestive heart failure and an LVEF of less than 50 percent who were referred to our institution for circumferential pulmonary vein isolation (CPVI) between the years 2016 and 2020. The selection criteria included a detailed medical history while excluding those suffering from valvular disease, congenital heart disease, and hypertrophic cardiomyopathy. In an effort to scrutinize varying etiologies, patients were stratified into three categories: dilated cardiomyopathy (DCM, n = 56, 30.6%), ischemic cardiomyopathy (ICM, n = 68, 37.2%), and tachycardia-induced cardiomyopathy (TIC, n = 59, 32.2%). (3) Results: Following an average (±SD) duration of 36 ± 3 months, the prevalence of sinus rhythm was 52.1% in the DCM group, 50.0% in the ICM group, and 68.14% in the TIC group (p = 0.014). This study revealed a significant disparity between the DCM and TIC groups (p = 0.021) and the ICM and TIC groups (p = 0.007), yet no significant distinction was discerned between the TIC and ICM groups (p = 0.769). Importantly, there were no significant variations in the application of antiarrhythmic drugs or recurrence of procedures among the three groups. The mortality rates were 14.29% for the DCM group and 14.71% for the ICM group, which were higher than the 3.39% observed in the TIC group (DCM vs. TIC p = 0.035 (HR = 4.50 (95%CI 1.38-14.67)), ICM vs. TIC p = 0.021 (HR = 5.00 (95%CI 1.61-15.50))). A noteworthy enhancement in heart function was evidenced in the TIC group in comparison to the DCM and ICM groups, including a higher LVEF (p < 0.001), diminution of LV end-diastolic diameter (p < 0.001), and an enhanced New York Heart Association classification (p = 0.005). Hospitalization rates for heart failure were discernibly lower in TIC patients (0.98 (0,2) times) relative to those with DCM (1.74 (0,3) times, p < 0.01) and TIC (1.78 (0,4) times, p < 0.001). Patients with paroxysmal atrial fibrillation and brief episodes were found to achieve superior clinical outcomes through a catheter ablation strategy. (4) Conclusion: Patients diagnosed with TIC demonstrated a more pronounced benefit from catheter ablation compared to those with DCM and ICM. This encompassed an augmented improvement in cardiac function, an enhanced maintenance of sinus rhythm, and a reduced mortality rate.

SAT504 Thyroidal Pax de Deux: 2 Cases of Resistance to Thyroid Hormone and Coexisting Thyroid Disease

Abstract Disclosure: S.V. Ribeiro: None. T. Moreno: None. A. Varela: None. P. Freitas: None. D.M. Carvalho: None. Resistance to thyroid hormone (RTH) is a rare clinical syndrome defined by hyposensitivity to thyroid hormone (TH) and characterized by elevated TH levels in the absence of TSH suppression. In most subjects with RTH, treatment is not required as tissue resistance is adequately compensated for by an increase in the endogenous supply of TH. This is not the case in patients with limited thyroidal reserve. Here we describe the clinical features of two unrelated patients with RTH and coexisting thyroid disease. Patient 1 was an 18-year-old female medical student referred to our consultation from Pediatrics. She had been diagnosed with autoimmune thyroiditis at age of 7 following the development of an obvious goiter. By then her thyroid-function tests (TFT) showed elevated TSH (8.75 µIU/mL, NR 0.41-3.67) and a normal free T4 (1.3 ng/dL, NR 0.82-1.76). She tested positive for the presence of antibodies to thyroperoxidase and thyroglobulin. The cytological findings on aspiration biopsy were consistent with Hashimoto’s thyroiditis. Throughout the years, despite levothyroxine supplementation she displayed systematically elevated TSH and normal FT4. The results of a thyrotropin stimulation test were normal. The suspicious of erratic compliance to therapy was raised.Follow-up at our outpatient clinic confirmed requirement for unusually high replacement doses of levothyroxine in order to maintain TSH within normal limits at expense of elevated FT4 and FT3 levels, suggesting the possibility of RTH. She was found with a THRβ c.1292T&amp;gt;C p.(Iso431Thr) heterozygous mutation. She remains clinically euthyroid under supplementation. Patient 2 was an asymptomatic 54-year-old female who consulted us for further evaluation of a thyroid nodule. Thyroid-FT showed an elevated FT3, at 3.86 μg/dL (NR, 1.75 to 3.71), an elevated FT4 at 1.86 ng/dL (NR 0.70 to 1.48), and a normal TSH level at 1.55 µIU/mL (NR, 0.40 to 4.50). A diffuse goiter was revealed by scintigraphy and the ultrasound showed no relevant findings. A diagnosis of RTH was genetically confirmed (THRβ c.1707C&amp;gt;G p.(P453A)). After a 6-year follow-up, she was diagnosed with supraventricular tachyarrhythmia for which she was started on amiodarone. Shortly after, her TFT revealed elevated TSH that normalized a few months after amiodarone withdrawal. Three years later, she was admitted to the intensive care unit due to cardiogenic shock attributed to tachycardia-induced cardiomyopathy and restarted on amiodarone. Her subsequent TFT showed elevated TSH (42.07 µIU/mL), with decreasing levels of TH (FT3 2.02 μg/dL, FT4 1.06 ng/dL). A diagnosis of amiodarone-induced hypothyroidism was made and levothyroxine supplementation was initiated and adjusted considering the patient’s symptoms. These cases show that the coexistence of RTH with other thyroidal disease can make diagnosis and management challenging and requires awareness and long-term follow-up. Presentation Date: Saturday, June 17, 2023