Catheter Ablation as First-Line Therapy in Persistent Atrial Fibrillation: Patient Characteristics and Clinical Outcomes.

BACKGROUND: In patients with persistent atrial fibrillation (PerAF), antiarrhythmic drugs (AADs) are considered a first-line rhythm-control strategy, whereas catheter ablation is a reasonable alternative. OBJECTIVES: This study sought to examine the prevalence, patient characteristics, and clinical outcomes of patients with PerAF who underwent catheter ablation as a first or second-line strategy. METHODS: This multicenter observational study included consecutive patients with PerAF who underwent first-time ablation between January 2020 and September 2021 in 9 medical centers in the United States. Patients were divided into those who underwent ablation as first-line therapy and those who had ablation as second-line therapy. Patient characteristics and clinical outcomes were compared between the groups. RESULTS: A total of 2,083 patients underwent first-time ablation for PerAF. Of these, 1,086 (52%) underwent ablation as a first-line rhythm-control treatment. Compared with patients treated with AADs as first-line therapy, these patients were predominantly male (72.6% vs 68.1%; P = 0.03), with a lower frequency of hypertension (64.0% vs 73.4%; P < 0.001) and heart failure (19.1% vs 30.5%; P < 0.001). During a mean follow-up of 325.9 ± 81.6 days, arrhythmia-free survival was similar between the groups (HR: 1.13; 95% CI: 0.92-1.41); however, patients in the second-line ablation strategy were more likely to continue receiving AAD therapy (41.5% vs 15.9%; P < 0.001). CONCLUSIONS: A first-line ablation strategy for PerAF is prevalent in the United States, particularly in men with fewer comorbidities. More data are needed to identify patients with PerAF who derive benefit from an early intervention strategy.

Development and validation of the Atri-Risk Conduction Index risk score to predict risk of atrial fibrillation after typical atrial flutter ablation.

BACKGROUND: Identification of patients at risk for atrial fibrillation (AF) after typical atrial flutter (tAFL) ablation is important to guide monitoring and treatment. OBJECTIVE: The purpose of this study was to create and validate a risk score to predict AF after tAFL ablation METHODS: We identified patients who underwent tAFL ablation with no AF history between 2017 and 2022 and randomly allocated to derivation and validation cohorts. We collected clinical variables and measured conduction parameters in sinus rhythm on an electrophysiology recording system (CardioLab, GE Healthcare). Univariate and multivariate logistic regressions (LogR) were used to evaluate association with AF development. RESULTS: A total of 242 consecutive patients (81% male; mean age 66 ± 11 years) were divided into derivation (n =142) and validation (n = 100) cohorts. Forty-two percent developed AF over median follow-up of 330 days. In multivariate LogR (derivation cohort), proximal to distal coronary sinus time (pCS-dCS) ≥70 ms (odds ratio [OR] 16.7; 95% confidence interval [CI] 5.6-49), pCS time ≥36 ms (OR 4.5; 95% CI 1.5-13), and CHADS2-VASc score ≥3 (OR 4.3; 95% CI 1.6-11.8) were independently associated with new AF during follow-up. The Atri-Risk Conduction Index (ARCI) score was created with 0 as minimal and 4 as high-risk using pCS-dCS ≥70 ms = 2 points; pCS ≥36 ms = 1 point; and CHADS2-VASc score ≥3 = 1 point. In the validation cohort, 0% of patients with ARCI score = 0 developed AF, whereas 89% of patients with ARCI score = 4 developed AF. CONCLUSION: We developed and validated a risk score using atrial conduction parameters and clinical risk factors to predict AF after tAFL ablation. It stratifies low-, moderate-, and high-risk patients and may be helpful in individualizing approaches to AF monitoring and anticoagulation.

Evaluating temperature gradients across the posterior left atrium with radiofrequency ablation.

INTRODUCTION: Esophageal injury is a well-known complication associated with catheter ablation. Though novel methods to mitigate esophageal injury have been developed, few studies have evaluated temperature gradients with catheter ablation across the posterior wall of the left atrium, interstitium, and esophagus. METHODS: To investigate temperature gradients across the tissue, we developed a porcine heart-esophageal model to perform ex vivo catheter ablation on the posterior wall of the left atrium (LA), with juxtaposed interstitial tissue and esophagus. Circulating saline (5 L/min) was used to mimic blood flow along the LA and alteration of ionic content to modulate impedance. Thermistors along the region of interest were used to analyze temperature gradients. Varying time and power, radiofrequency (RF) ablation lesions were applied with an externally irrigated ablation catheter. Ablation strategies were divided into standard approaches (SAs, 10-15 g, 25-35 W, 30 s) or high-power short duration (HPSD, 10-15 g, 40-50 W, 10 s). Temperature gradients, time to the maximum measured temperature, and the relationship between measured temperature as a function of distance from the site of ablation was analyzed. RESULTS: In total, five experiments were conducted each utilizing new porcine posterior LA wall-esophageal specimens for RF ablation (n = 60 lesions each for SA and HPSD). For both SA and HPSD, maximum temperature rise from baseline was markedly higher at the anterior wall (AW) of the esophagus compared to the esophageal lumen (SA: 4.29°C vs. 0.41°C, p < .0001 and HPSD: 3.13°C vs. 0.28°C, p < .0001). Across ablation strategies, the average temperature rise at the AW of the esophagus was significantly higher with SA relative to HPSD ablation (4.29°C vs. 3.13°C, p = .01). From the start of ablation, the average time to reach a maximum temperature as measured at the AW of the esophagus with SA was 36.49 ± 12.12 s, compared to 16.57 ± 4.54 s with HPSD ablation, p < .0001. Fit to a linear scale, a 0.37°C drop in temperature was seen for every 1 cm increase in distance from the site of ablation and thermistor location at the AW of the esophagus. CONCLUSION: Both SA and HPSD ablation strategies resulted in markedly higher temperatures measured at the AW of the esophagus compared to the esophageal lumen, raising concern about the value of clinical intraluminal temperature monitoring. The temperature rise at the AW was lower with HPSD. A significant time delay was seen to reach the maximum measured temperature and a modest increase in distance between the site of ablation and thermistor location impacted the accuracy of monitored temperatures.

Right Ventricular Dysfunction During Endurance Exercise as Determined by Pressure-Volume Analysis.

A 37-year-old athlete completed invasive endurance (90 km) bicycle exercise testing for right ventricular pressure-volume analysis. Increased right ventricular afterload caused declines in ventricular-arterial coupling and cardiac output, causing increased arteriovenous oxygen difference to maintain oxygen uptake. These findings demonstrate effects of changes in right ventricular performance on exercise capacity. (Level of Difficulty: Intermediate.).

Limitations of Unipolar Signals in Guiding Successful Outflow Tract Premature Ventricular Contraction Ablation.

BACKGROUND: Unipolar electrograms (UniEGMs) are commonly used to annotate earliest local activation of focal arrhythmias. However, their utility in guiding premature ventricular contractions (PVCs) ablation may be limited when the PVC source is less superficial. OBJECTIVES: The authors sought to compare bipolar electrograms (BiEGMs) vs UniEGMs in guiding successful ablation of right ventricular outflow tract (RVOT) vs intramural outflow tract (OT) PVCs. The authors hypothesized that: 1) earliest bipolar local activation time (LATBi) would better guide mapping and ablation, vs UniEGM dV/dt (LATUni) or QS morphology; and 2) LAT differences using bipolar vs unipolar EGMs (ΔLATBi-Uni) would be greater for intramural OT than RVOT PVCs. METHODS: Consecutive patients undergoing successful PVC ablation 2017 to2020 requiring only RVOT or RVOT+left ventricular OT (RVOT+LVOT) ablation were retrospectively analyzed. BiEGMs and UniEGMs at successful ablation sites were compared. RESULTS: Of 70 patients, 50 required RVOT-only, and 20 required RVOT+LVOT ablation for acute and long-term PVC suppression. Mean ΔLATBi-Uni was lower for RVOT vs RVOT+LVOT groups (9.3 ± 6.4 ms vs 17.4 ± 9.9 ms; P < 0.01). QS UniEGM was seen in 78% of RVOT, compared with 53% of RVOT+LVOT patients (P < 0.016). RVOT+LVOT sites most frequently included the posteroseptal RVOT and adjacent LVOT (73%), and 43% lacked a QS unipolar EGM. ΔLATBi-Uni ≥15 ms best distinguished sites in which RVOT-only vs RVOT+LVOT ablation achieved acute PVC suppression (area under the curve: 0.77). CONCLUSIONS: Earliest BiEGM activation guides successful ablation of OT PVCs better than UniEGM-guided analysis, especially when an intramural PVC source is present.

New insights into resting and exertional right ventricular performance in the healthy heart through real-time pressure-volume analysis.

KEY POINTS: Despite growing interest in right ventricular form and function in diseased states, there is a paucity of data regarding characteristics of right ventricular function - namely contractile and lusitropic reserve, as well as ventricular-arterial coupling, in the healthy heart during rest, as well as submaximal and peak exercise. Pressure-volume analysis of the right ventricle, during invasive cardiopulmonary exercise testing, demonstrates that that the right heart has enormous contractile reserve, with a three- or fourfold increase in all metrics of contractility, as well as myocardial energy production and utilization. The healthy right ventricle also demonstrates marked augmentation in lusitropy, indicating that diastolic filling of the right heart is not passive. Rather, the right ventricle actively contributes to venous return during exercise, along with the muscle pump. Ventricular-arterial coupling is preserved during submaximal and peak exercise in the healthy heart. ABSTRACT: Knowledge of right ventricular (RV) function has lagged behind that of the left ventricle and historically, the RV has even been referred to as a 'passive conduit' of lesser importance than its left-sided counterpart. Pressure-volume (PV) analysis is the gold standard metric of assessing ventricular performance. We recruited nine healthy sedentary individuals free of any cardiopulmonary disease (42 ± 12 years, 78 ± 11 kg), who completed invasive cardiopulmonary exercise testing during upright ergometry, while using conductance catheters inserted into the RV to generate real-time PV loops. Data were obtained at rest, two submaximal levels of exercise below ventilatory threshold, to simulate real-world scenarios/activities of daily living, and maximal effort. Breath-by-breath oxygen uptake was determined by indirect calorimetry. During submaximal and peak exercise, there were significant increases in all metrics of systolic function by three- to fourfold, including cardiac output, preload recruitable stroke work, and maximum rate of pressure change in the ventricle (dP/dtmax ), as well as energy utilization as determined by stroke work and pressure-volume area. Similarly, the RV demonstrated a significant, threefold increase in lusitropic reserve throughout exercise. Ventricular-arterial coupling, defined by the quotient of end-systolic elastance and effective arterial elastance, was preserved throughout all stages of exercise. Maximal pressures increased significantly during exercise, while end-diastolic volumes were essentially unchanged. Overall, these findings demonstrate that the healthy RV is not merely a passive conduit, but actively participates in cardiopulmonary performance during exercise by accessing an enormous amount of contractile and lusitropic reserve, ensuring that VA coupling is preserved throughout all stages of exercise.

Red Blood Cell Fragmentation Syndrome After Placement of MitraClip.

An 87-year-old woman with a history of trastuzumab-induced left ventricular dysfunction underwent the MitraClip (Abbott Vascular, Santa Clara, California) procedure for myxomatous mitral regurgitation. She presented a month later with severe intravascular hemolytic anemia, attributed to the MitraClip. She underwent surgical mitral valve replacement and had resolution of hemolysis. (Level of Difficulty: Advanced.).

Natural History of Patients Postacute Coronary Syndrome Based on Heart Failure Status.

The natural history of patients hospitalized for acute coronary syndrome (ACS) with pre-existing versus (vs) de novo heart failure (HF) has not been previously reported over an extended duration of follow-up. The IMPROVE-IT trial enrolled 18,144 patients hospitalized for ACS and randomized them to combination simvastatin (40 mg)/ezetimibe (10 mg) vs simvastatin (40 mg). Subjects were divided into 3 groups: pre-existing HF (i.e., defined by past medical history), de novo HF (i.e., defined by Killip class II or greater during index admission), and no HF. The final analytical cohort included 14,792 patients (82%) with HF status recorded at baseline. In total, 790 patients (5.3%) reported a pre-existing diagnosis of HF and 1374 patients (9.3%) experienced de novo HF. Patients with pre-existing or de novo HF were older, more likely to be woman, and had a greater prevalence of atrial fibrillation and diabetes mellitus. The incidences of death/HF-hospitalizations at 5 years were 32%/20% for pre-existing HF, 18%/7% for de novo HF, and 8%/3% for no HF. After adjusting for potential confounders, a history of pre-existing or de novo HF was independently associated with increased risk of death (pre-existing HF: hazard ratio [HR] 1.93, 95% confidence interval [CI] 1.68 to 2.22, p < 0.001; de novo HF: HR 1.51, 95% CI 1.33 to 1.72, p < 0.001) and hospitalizations for HF (pre-existing HF: HR 2.96, 95% CI 2.36 to 3.71, p < 0.001; de novo HF: HR 1.88, 95% CI 1.49 to 2.38, p < 0.001). There was no interaction among baseline HF status (i.e., pre-existing or de novo), lipid lowering therapy (i.e., simvastatin/ezetimibe vs simvastatin alone), and clinical outcomes. In conclusion, patients hospitalized for ACS with pre-existing or de novo HF were older and had a greater burden of medical co-morbidities. In conclusion, HF was independently associated with increased risk of long-term morbidity and mortality with the pre-existing HF cohort demonstrating the highest overall risk.

Post-Traumatic Stress Disorder and Heart Failure in Men Within the Veteran Affairs Health System.

Patients with post-traumatic stress disorder (PTSD) are at risk of multiple co-morbidities and are more likely to develop incident heart failure with reduced ejection fraction (HFrEF). The relation of PTSD with clinical outcomes in HFrEF is not established. US veterans diagnosed with HFrEF from January 2007 to January 2015 and treated nationwide in the Veterans Affairs (VA) Health System were included in the study. Patients with HFrEF were identified through International Classification of Diseases, Ninth Revision (ICD-9) codes. Mortality data were obtained from the VA's death registry. We compared characteristics of patients with HFrEF with and without PTSD. We identified 111,970 VA patients with HFrEF and 11,039 patients with concomitant PTSD (9.9%). Patients with PTSD and HFrEF tended to be younger (64 vs 69 years) and have a higher rate of coronary artery disease (73% vs 64%), chronic obstructive pulmonary disease (42% vs 31%), and hypertension (80% vs 64%, p <0.01 for all variables). Patients with PTSD and HFrEF were more commonly on a high-dose ß blocker (70% vs 68%, p <0.01) and angiotensin-converting enzyme inhibitors (96% vs 93%, p <0.01). PTSD was associated with significantly increased mortality at 7 years compared with patients with heart failure without PTSD (adjusted 1.54, 95% confidence interval 1.30 to 1.82, p <0.01). In conclusion, nearly 10% of veterans with HFrEF have PTSD. Patients with HFrEF with PTSD have a higher burden of co-morbidities, and PTSD is associated with a higher rate of all-cause death. Our findings support greater attention to the treatment of patients with PTSD and the causes associated with the poor outcomes.

Is Time of the Essence? The Impact of Time of Hospital Presentation in Acute Heart Failure: Insights From ASCEND-HF Trial.

OBJECTIVES: As the largest acute heart failure (AHF) trial conducted to date, the global ASCEND-HF (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure) trial database presented an opportunity to systematically describe the relationship among time of hospital presentation, clinical profile, inpatient management, and outcomes among patients admitted with AHF. BACKGROUND: Time of hospital presentation has been shown to impact outcomes among patients hospitalized with many conditions. However, the association among time of presentation and patient characteristics, management, and clinical outcomes among patients hospitalized with AHF has not been well characterized. METHODS: A post hoc analysis of the ASCEND-HF trial was performed, which enrolled 7,141 patients hospitalized for AHF. Patients were divided based on when they presented to the hospital; regular hours were defined as 9 am to 5 pm, Monday through Friday, and off hours were defined as 5 pm to 9 am, Monday through Friday and weekends. Clinical characteristics and outcomes were compared by time of presentation. RESULTS: Overall, 3,298 patients (46%) presented during off hours. Off-hour patients were more likely to have orthopnea (80% vs. 74%, respectively) and rales (56% vs. 49%, respectively) than regular-hour patients. Off-hour patients were more likely to receive intravenous (IV) nitroglycerin (18% vs. 11%, respectively) and IV loop diuretics (92% vs. 86%, respectively) as initial therapy and reported greater relief from dyspnea at 24 h (odds ratio [OR]: 1.14; 95% confidence interval [CI]: 1.04 to 1.24; p = 0.01) than regular-hour patients. After adjustment, off-hour presentation was associated with significantly lower 30-day mortality (OR: 0.74; 95% CI: 0.57 to 0.96; p = 0.03) and 180-day mortality (hazard ratio [HR]: 0.82; 95% CI: 0.72 to 0.94; p = 0.01) but similar 30-day rehospitalization rates (p = 0.40). CONCLUSIONS: In this AHF trial, patients admitted during off hours exhibited a distinct clinical profile, experienced greater dyspnea relief, and had lower post-discharge mortality than regular-hour patients. These findings have implications for future AHF trials.

Hospitalization for Recently Diagnosed Versus Worsening Chronic Heart Failure: From the ASCEND-HF Trial.

BACKGROUND: It is unclear how patients hospitalized for acute heart failure (HF) who are long-term chronic HF survivors differ from those with more recent HF diagnoses. OBJECTIVES: The goal of this study was to evaluate the influence of HF chronicity on acute HF patient profiles and outcomes. METHODS: The ASCEND-HF (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure) trial randomized 7,141 hospitalized patients with acute HF with reduced or preserved ejection fraction (EF) to receive nesiritide or placebo in addition to standard care. The present analysis compared patients according to duration of HF diagnosis before index hospitalization by using pre-specified cutoffs (0 to 1 month [i.e., "recently diagnosed"], >1 to 12 months, >12 to 60 months, and >60 months). RESULTS: Overall, 5,741 (80.4%) patients had documentation of duration of HF diagnosis (recently diagnosed, n = 1,536; >1 to 12 months, n = 1,020; >12 to 60 months, n = 1,653; and >60 months, n = 1,532). Across HF duration groups, mean age ranged from 64 to 66 years, and mean ejection fraction ranged from 29% to 32%. Compared with patients with longer HF duration, recently diagnosed patients were more likely to be women with nonischemic HF etiology, higher baseline blood pressure, better baseline renal function, and fewer comorbidities. After adjustment, compared with recently diagnosed patients, patients with longer HF duration were associated with more persistent dyspnea at 24 h (>1 to 12 months, odds ratio [OR]: 1.20; 95% confidence interval [CI]: 0.97 to 1.48; >12 to 60 months, OR: 1.34; 95% CI: 1.11 to 1.62; and >60 months, OR: 1.31; 95% CI: 1.08 to 1.60) and increased 180-day mortality (>1 to 12 months, hazard ratio [HR]: 1.89; 95% CI: 1.35 to 2.65; >12 to 60 months, HR: 1.82; 95% CI: 1.33 to 2.48; and >60 months, HR: 2.02; 95% CI: 1.47 to 2.77). The influence of HF duration on mortality was potentially more pronounced among female patients (interaction p = 0.05), but did not differ according to age, race, prior ischemic heart disease, or ejection fraction (all interactions, p ≥ 0.23). CONCLUSIONS: In this acute HF trial, patient profile differed according to duration of the HF diagnosis. A diagnosis of HF for ≤1 month before hospitalization was independently associated with greater early dyspnea relief and improved post-discharge survival compared to patients with chronic HF diagnoses. The distinction between de novo or recently diagnosed HF and worsening chronic HF should be considered in the design of future acute HF trials. (A Study Testing the Effectiveness of Nesiritide in Patients With Acute Decompensated Heart Failure; NCT00475852).

Aerobic exercise training and general health status in ambulatory heart failure patients with a reduced ejection fraction-Findings from the Heart Failure and A Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION)trial.

BACKGROUND: Although aerobic exercise improves quality of life as assessed by a disease-specific instrument in ambulatory HF patients with a reduced ejection fraction (EF), the impact of an exercise intervention on general health status has not been previously reported. METHODS: A secondary analysis was performed of the HF-ACTION trial (ClinicalTrials.gov Number: NCT00047437), which enrolled 2331 medically stable outpatients with HF and an EF ≤35% and randomized them to aerobic exercise training, consisting of 36 supervised sessions followed by home-based training versus usual care for a median follow-up of 30 months. The EuroQOL 5-dimension questionnaire (EQ-5D) was administered to study participants at baseline, 3 months, and 12 months. EQ-5D includes functional dimensions (ie, mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), which were mapped to corresponding utility scores (ie, 0=death and 1=perfect health), and a visual analogue scale (VAS) ranging from 0 (ie, "worst imaginable health state") to 100 (ie, "best imaginable health state"). RESULTS: Study participants had a median (25th, 75th) age of 59 (51, 68) years and 71% were male. A history of ischemic heart disease was reported in 51% of participants and the EF was 25% (20%, 30%). Baseline VAS and mapped utility scores were 65±19 and 0.81±0.14. Exercise training led to an improvement in VAS score compared with usual care from baseline to 3 months (exercise training: 6±17 vs usual care: 3±20; P <.01) although there were no further significant changes at 12 months. Aerobic exercise training did not favorably change mapped utility scores over either timeframe. After multivariable adjustment, lower mapped utility (hazard ratio [HR] 1.19 per 0.1 decrease, 95% CI 1.09-1.29; P < .0001) and VAS scores (HR 1.05 per 10 point decrease, 95% CI 1.02-1.08; P < .01) at baseline were associated with increased risk of death or hospitalization. CONCLUSION: Ambulatory HF patients with a reduced EF had impaired health status at baseline which was associated with increased morbidity and mortality, in part mitigated by a structured aerobic exercise regimen.

Body Weight Change During and After Hospitalization for Acute Heart Failure: Patient Characteristics, Markers of Congestion, and Outcomes: Findings From the ASCEND-HF Trial.

OBJECTIVES: This study sought to examine the relationships between in-hospital and post-discharge body weight changes and outcomes among patients hospitalized for acute heart failure (AHF). BACKGROUND: Body weight changes during and after hospitalization for AHF and the relationships with outcomes have not been well characterized. METHODS: A post hoc analysis was performed of the ASCEND-HF (Acute Study of Clinical Effectiveness of Nesiritide and Decompensated Heart Failure) trial, which enrolled patients admitted for AHF regardless of ejection fraction. In-hospital body weight change was defined as the difference between baseline and discharge/day 10, whereas post-discharge body weight change was defined as the difference between discharge/day 10 and day 30. Spearman rank correlations of weight change, urine output (UOP), and dyspnea relief as assessed by a 7-point Likert scale are described. Logistic and Cox proportional hazards regression was used to evaluate the relationship between weight change and outcomes. RESULTS: Study participants with complete body weight data (n = 4,172) had a mean age of 65 ± 14 years, and 66% were male. Ischemic heart disease was reported in 60% of patients and the average ejection fraction was 30 ± 13%. The median change in body weight was -1.0 kg (interquartile range: -2.1 to 0.0 kg) at 24 h and -2.3 kg (interquartile range: -5.0 to -0.7 kg) by discharge/day 10. At hour 24, there was a weak correlation between change in body weight and UOP (r = -0.381), and minimal correlation between body weight change and dyspnea relief (r = -0.096). After risk adjustment, increasing body weight during hospitalization was associated with a 16% increase per kg in the likelihood of 30-day mortality or HF readmission for patients showing weight loss ≤1 kg or weight gain during hospitalization (odds ratio per kg increase 1.16, 95% confidence interval [CI]: 1.09 to 1.27; p < 0.001). Among the subset of patients experiencing >1-kg increase in body weight post-discharge, increasing body weight was associated with higher risk of 180-day mortality (hazard ratio per kg increase 1.16; 95% CI: 1.09 to 1.23; p < 0.001). CONCLUSIONS: A substantial number of patients experienced minimal weight loss or frank weight gain in the context of an AHF trial, and increasing body weight in this subset of patients was independently associated with a worse post-discharge prognosis.