Evaluating cardiac lead safety using observational, real-world data: EP PASSION proof-of-concept study.

BACKGROUND: Traditional post-approval study (PAS) designs have been accepted by regulatory authorities to fulfill postmarketing requirements for cardiac leads, but they have several limitations. OBJECTIVE: We conducted a proof-of-concept study of alternative methods that use real-world data (RWD) to evaluate lead safety in large populations of patients. METHODS: Abbott patient device databases were linked with Medicare Fee-For-Service (FFS) claims to identify lead complications in patients implanted with Abbott Optisure lead. A 1:1 comparison between the PAS method and RWD method of detecting mechanical lead-related complication events was conducted in 444 PAS participants who were enrolled in Medicare FFS. Agreement between methods was evaluated by McNemar test and Cohen κ. Survival free from complications at 3 years was compared between the PAS and RWD cohorts with an equivalence acceptance criterion of ±2.5%. RESULTS: There were 1171 PAS patients and 5804 Medicare FFS patients who received an Optisure lead between August 27, 2014, and June 14, 2016. Patients were observed through December 31, 2018. Complete agreement was found between PAS-reported and claims-detected complications (McNemar P value = 1; Cohen κ = 1). Survival free from complications at 3 years by the RWD method was 98.4% (95% confidence limit, 98.0%-98.7%), which was within the acceptable range of the PAS 98.4% (95% confidence limit, 97.6%-99.0%). CONCLUSION: These results show a close agreement between RWD-detected and PAS-reported lead complication rates, which highlights the potential benefits of RWD-based methods to enhance the generation of clinical evidence for lead safety.

Longitudinal Assessment of Left Atrial Remodeling in Patients With Chronic Severe Aortic Regurgitation.

BACKGROUND: There are significant sex and age differences in left ventricular (LV) remodeling that may lead to disparity in outcomes when used to inform the timing of aortic regurgitation (AR) intervention. OBJECTIVES: The aim of this study was to examine whether left atrial (LA) parameters might represent better criteria than LV parameters to inform the timing of AR intervention. METHODS: Using data on patients with moderate to severe or severe AR with serial echocardiography (2010-2016), the longitudinal trends in left atrial volume index (LAVI) and left atrial reservoir strain (LAr) were evaluated by sex and age. The incremental utility of these parameters in predicting adverse events over LV parameters was also determined. RESULTS: In 525 patients (25.7% women) with 1,687 echocardiograms over a median follow-up period of 2.0 years (Q1-Q3: 1.0-3.6 years), there was significant increase in LAVI (1.0 mL/m2 per year [95% CI: 0.76-1.2 mL/m2 per year]) and decrease in LAr (-1.3% per year [95% CI: -1.6% to -0.92%]), without a significant interaction by sex or age category (P for interaction ≥ 0.17). In addition, both LAVI and LAr were significant predictors of adverse events independent of LV parameters. The optimal discriminatory thresholds were 37 mL/m2 for LAVI and 35% for LAr. These thresholds were similar across categories of sex and age. Within the relatively short-term follow-up, surgery was associated with survival benefit among patients with LAVI ≥37 mL/m2 (HR: 0.33 [95% CI: 0.15-0.72]; P = 0.006) but was not statistically significant among patients with LAVI <37 mL/m2 (HR: 0.46 [95% CI: 0.18-1.17]; P = 0.09). Similarly, surgery was associated with survival for the subgroup with LAr ≤35% but not among those with LAr >35%. CONCLUSIONS: Unlike LV remodeling, LA remodeling demonstrates a similar rate of progression between categories of sex and age among patients with AR. In addition, LA parameters provide incremental prognostic value over LV parameters.

Alterations in the sarcopenia index are associated with inflammation, gut, and oral microbiota among heart failure, left ventricular assist device, and heart transplant patients.

BACKGROUND: Sarcopenia, characterized by loss of muscle mass and function, is prevalent in heart failure (HF) and predicts poor outcomes. We investigated alterations in sarcopenia index (SI), a surrogate for skeletal muscle mass, in HF, left ventricular assist device (LVAD), and heart transplant (HT), and assessed its relationship with inflammation and digestive tract (gut and oral) microbiota. METHODS: We enrolled 460 HF, LVAD, and HT patients. Repeated measures pre/post-procedures were obtained prospectively in a subset of LVAD and HT patients. SI (serum creatinine/cystatin C) and inflammatory biomarkers (C-reactive protein, interleukin-6, tumor necrosis factor-alpha) were measured in 271 and 622 blood samples, respectively. Gut and saliva microbiota were assessed via 16S ribosomal ribonucleic acid sequencing among 335 stool and 341 saliva samples. Multivariable regression assessed the relationship between SI and (1) New York Heart Association class; (2) pre- versus post-LVAD or HT; and (3) biomarkers of inflammation and microbial diversity. RESULTS: Median (interquartile range) natural logarithm (ln)-SI was -0.13 (-0.32, 0.05). Ln-SI decreased across worsening HF class, further declined at 1 month after LVAD and HT, and rebounded over time. Ln-SI was correlated with inflammation (r = -0.28, p < 0.01), gut (r = 0.28, p < 0.01), and oral microbial diversity (r = 0.24, p < 0.01). These associations remained significant after multivariable adjustment in the combined cohort but not for all individual cohorts. The presence of the gut taxa Roseburia inulinivorans was associated with increased SI. CONCLUSIONS: SI levels decreased in symptomatic HF and remained decreased long-term after LVAD and HT. In the combined cohort, SI levels covaried with inflammation in a similar fashion and were significantly related to overall microbial (gut and oral) diversity, including specific taxa compositional changes.

Cryoballoon pulmonary vein isolation versus radiofrequency ablation of the pulmonary veins and left atrial posterior wall: Patient-reported outcomes.

BACKGROUND: Data are lacking on patient-reported outcomes (PRO) following cryoballoon ablation (CBA) versus radiofrequency ablation (RFA). We sought to evaluate QoL and clinical outcomes of cryoballoon pulmonary vein isolation only (CRYO-PVI-ONLY) versus RFA with PVI and posterior wall isolation (RF-PVI+PWI) in a large prospective PRO registry. METHODS: Patients who underwent AF ablation (2013-2016) at our institution were enrolled in an automated, prospectively maintained PRO registry. CRYO-PVI-ONLY patients were matched (1:1) with RF-PVI+PWI patients based on age, gender, and type of AF (paroxysmal vs. persistent). QoL and clinical outcomes were assessed using PRO surveys at baseline and at 1-year. The atrial fibrillation symptom severity scale (AFSSS) was the measure for QoL. Additionally, we assessed patient-reported clinical improvement, arrhythmia recurrence, and AF burden (as indicated by AF frequency and duration scores). RESULTS: A total of 296 patients were included (148 in each group, 72% paroxysmal). By PRO, a significant improvement in QoL was observed in the overall study population and was comparable between CRYO-PVI-ONLY and RF-PVI+PWI (baseline median AFSSS of 11.5 and 11; reduced to 2 and 4 at 1 year, respectively; p = 0.44). Similarly, the proportion of patients who reported improvement in their overall QoL and AF related symptoms was high and similar between the study groups [92% (CRYO-PVI-ONLY) vs. 92.8% (RF-PVI+PWI); p = 0.88]. Arrhythmia recurrence was significantly more common in the CRYO-PVI-ONLY group (39.7%) compared to RF-PVI+PWI (27.7 %); p = 0.03. Comparable results were observed in paroxysmal and persistent AF. CONCLUSION: CRYO-PVI-ONLY and RF-PVI+PWI resulted in comparable improvements in patient reported outcomes including QoL and AF burden; with RF-PVI+PWI being more effective at reducing recurrences.

Antiplatelet Therapy, Abdominal Aortic Aneurysm Progression, and Clinical Outcomes.

Importance: Preclinical studies suggest a potential role for aspirin in slowing abdominal aortic aneurysm (AAA) progression and preventing rupture. Evidence on the clinical benefit of aspirin in AAA from human studies is lacking. Objective: To investigate the association of aspirin use with aneurysm progression and long-term clinical outcomes in patients with AAA. Design, Setting, and Participants: This was a retrospective, single-center cohort study. Adult patients with at least 2 available vascular ultrasounds at the Cleveland Clinic were included, and patients with history of aneurysm repair, dissection, or rupture were excluded. All patients were followed up for 10 years. Data were analyzed from May 2022 to July 2023. Main Outcomes and Measures: Clinical outcomes were time-to-first occurrence of all-cause mortality, major bleeding, or composite of dissection, rupture, and repair. Multivariable-adjusted Cox proportional-hazard regression was used to estimate hazard ratios (HR) for all-cause mortality, and subhazard ratios competing-risk regression using Fine and Gray proportional subhazards regression was used for major bleeding and composite outcome. Aneurysm progression was assessed by comparing the mean annualized change of aneurysm diameter using multivariable-adjusted linear regression and comparing the odds of having rapid progression (annual diameter change >0.5 cm per year) using logistic regression. Results: A total of 3435 patients (mean [SD] age 73.7 [9.0] years; 2672 male patients [77.5%]; 120 Asian, Hispanic, American Indian, or Pacific Islander patients [3.4%]; 255 Black patients [7.4%]; 3060 White patients [89.0%]; and median [IQR] follow-up, 4.9 [2.5-7.5] years) were included in the final analyses, of which 2150 (63%) were verified to be taking aspirin by prescription. Patients taking aspirin had a slower mean (SD) annualized change in aneurysm diameter (2.8 [3.0] vs 3.8 [4.2] mm per year; P = .001) and lower odds of having rapid aneurysm progression compared with patients not taking aspirin (adjusted odds ratio, 0.64; 95% CI, 0.49-0.89; P = .002). Aspirin use was not associated with risk of all-cause mortality (adjusted HR [aHR], 0.92; 95% CI, 0.79-1.07; P = .32), nor was aspirin use associated with major bleeding (aHR, 0.88; 95% CI, 0.76-1.03; P = .12), or composite outcome (aHR, 1.16; 95% CI, 0.93-1.45; P = .09) at 10 years. Conclusions: In this retrospective study of a clinical cohort of 3435 patients with objectively measured changes in aortic aneurysm growth, aspirin use was significantly associated with slower progression of AAA with a favorable safety profile.

Endocarditis after Transcatheter Aortic Valve Replacement.

Transcatheter aortic valve replacement (TAVR) use is gaining momentum as the mainstay for the treatment of aortic stenosis compared to surgical aortic valve replacement (SAVR). Unfortunately, TAVR-related infective endocarditis (TAVR-IE) is expected to be detected more and more as a result of the ever-expanding indications in younger patients. Given the overall poor prognosis of TAVR-IE, it is imperative that clinicians familiarize themselves with common presentations, major risk factors, diagnostic pitfalls, therapeutic approaches, and the prevention of TAVR-IE. Herein, we review all of the above in detail with the most updated available literature.

Catheter ablation of atrial fibrillation in elderly and very elderly patients: safety, outcomes, and quality of life.

BACKGROUND: Atrial fibrillation (AF) risk increases with age. We aim to assess the efficacy and safety of catheter ablation in the older population. METHODS: All patients undergoing AF ablation (2013-2021) at our institution were enrolled in a prospectively maintained registry. The primary endpoint was AF recurrence. Patients were divided into 3 groups: non-elderly (< 65 years), elderly (65-75 years), and very elderly (> 75 years). Patient surveys at baseline and during follow-up were used to calculate quality of life (QoL) metrics: the AF severity score as well as the AF burden. RESULTS: A total of 7020 patients were included (42% non-elderly, 42% elderly, and 16% very elderly). Periprocedural major complications were low (< 1.5%) and similar in all groups besides pericardial effusion which was more frequent with older age and similar between the elderly and very elderly. At 3 years, AF recurrence for persistent AF (PersAF) was highest in the very elderly group (48%), followed by the elderly group (42%), and was the lowest in the non-elderly group (36%). In paroxysmal AF (PAF), there was no difference in AF recurrence between the elderly and non-elderly, while the very elderly remained associated with a significantly increased risk. Multivariable Cox analysis confirmed these findings (PersAF; elderly: HR = 1.23, P = 0.003; very elderly: HR = 1.44, P < 0.001) (PAF; elderly: HR = 1.04, P = 0.62; very elderly: HR = 1.30, P = 0.01). Catheter ablation resulted in a significant improvement in quality of life, irrespective of age group. CONCLUSION: Catheter ablation in elderly and very elderly patients is safe, efficacious, and associated with QoL benefits. Overall, major complications were minimal and did not differ significantly between age groups, with the exception of pericardial effusions which were higher in the elderly and very elderly compared to non-elderly adults. Very elderly patients had a higher rate of AF recurrence when compared with elderly or non-elderly patients. Nevertheless, ablation resulted in a remarkable improvement in QoL and a reduction of AF burden and AF symptoms with a similar magnitude, irrespective of age.

Evaluating troponin elevation in patients with chronic kidney disease and suspected acute coronary syndrome.

Many patients with chronic kidney disease have chronically elevated cardiac troponin levels, and if they present with symptoms suggesting an acute coronary syndrome, it is often difficult to determine if this is the correct diagnosis. This article briefly reviews the major challenges in diagnosing acute coronary syndrome in patients with chronic kidney disease, describes the mechanisms and prognostic significance of troponin elevation in chronic kidney disease, and provides a diagnostic algorithm to risk-stratify patients with chronic kidney disease who have troponin elevation and suspected acute coronary syndrome.

Impact of obesity on catheter ablation of atrial fibrillation: Patient characteristics, procedural complications, outcomes, and quality of life.

INTRODUCTION: Obesity is a well-known risk factor for atrial fibrillation (AF). We aim to evaluate the effect of baseline obesity on procedural complications, AF recurrence, and symptoms following catheter ablation (CA). METHODS: All consecutive patients undergoing AF ablation (2013-2021) at our center were enrolled in a prospective registry. The study included all consecutive patients with available data on body mass index (BMI). Primary endpoint was AF recurrence based on electrocardiographic documentation. Patients were categorized into five groups according to their baseline BMI. Patients survey at baseline and at follow-up were used to calculate AF symptom severity score (AFSS) as well as AF burden (mean of AF duration score and AF frequency score; scale 0: no AF to 10: continuous and 9 frequencies/durations in between). Patients were scheduled for follow-up visits with 12-lead electrocardiogram at 3, 6, and 12 months after ablation, and every 6 months thereafter. RESULTS: A total of 5841 patients were included (17% normal weight, 34% overweight, 27% Class I, 13% Class II, and 9% Class III obesity). Major procedural complications were low (1.5%) among all BMI subgroups. At 3 years AF recurrence was the highest in Class III obesity patients (48%) followed by Class II (43%), whereas Class I, normal, and overweight had similar results with lower recurrence (35%). In multivariable analyses, Class III obesity (BMI ≥ 40) was independently associated with increased risk for AF recurrence (hazard ratio, 1.30; confidence interval, 1.06-1.60; p = .01), whereas other groups had similar risk in comparison to normal weight. Baseline AFSS was lowest in normal weight, and highest in Obesity-III, median (interquartile range) 10 (5-16) versus 15 (10-21). In all groups, CA resulted in a significant improvement in their AFSS with a similar magnitude among the groups. At follow-up, AF burden was minimal and did not differ significantly between the groups. CONCLUSION: AF ablation is safe with a low complication rate across all BMI groups. Morbid obesity (BMI ≥ 40) was significantly associated with reduced AF ablation success. However, ablation resulted in improvement in QoL including reduction of the AFSS, and AF burden regardless of BMI.

Clinical outcomes following tricuspid transcatheter edge-to-edge repair with PASCAL: A meta-analysis.

BACKGROUND: Patients with severe tricuspid regurgitation (TR) exhibit high morbidity and mortality. Tricuspid transcatheter edge-to-edge repair (T-TEER) is a rapidly evolving strategy to address the unmet clinical need of severe TR therapies. OBJECTIVE: Organize the current body of evidence on outcomes following use of the PASCAL (Edwards Lifesciences) system for T-TEER. METHODS: For this meta-analysis, we searched the MEDLINE/PubMed, Embase, and Cochrane databases for keywords ["tricuspid"] and ["transcatheter" or "edge-to-edge"] and ["PASCAL" or "leaflet repair" or "valve repair"] from the database inception until January 11, 2023. Primary outcomes of interest were procedural success, mortality, New York Heart Association (NYHA) functional class, 6-min walking distance (6MWD), and TR severity. RESULTS: A total of 549 patients undergoing PASCAL or PASCAL Ace T-TEER were included. The mean age ranged from 71.0 to 80.3 years, with 25.0 to 63.6% females. The follow-up duration ranged from 30 days to 1 year. The success rate was 83.5% (409/490). There was improvement in symptoms based on NYHA classification (at 1- to 6-months; NYHA ≥3 RR 0.27 [95% CI 0.19-0.39]; p < 0.001) and 6MWD (at 1-month; 50.96 [95% CI 32.34-69.59]; p < 0.001) post-procedure. On imaging, there was improvement in TR severity post-procedure (at 1- to 12-months; ≥ severe TR 0.21 [95% CI 0.14-0.31]; p < 0.001), which remained significant with each study removed. CONCLUSION: PASCAL for T-TEER is associated with high procedural success rates along with improvements in NYHA functional class, TR severity, 6MWD, and patient-reported outcomes.

The Difference Between Cystatin C- and Creatinine-Based Estimated GFR in Heart Failure With Reduced Ejection Fraction: Insights From PARADIGM-HF.

RATIONALE & OBJECTIVE: The clinical implications of the discrepancy between cystatin C (cysC)- and serum creatinine (Scr)-estimated glomerular filtration rate (eGFR) in patients with heart failure (HF) and reduced ejection fraction (HFrEF) are unknown. STUDY DESIGN: Post-hoc analysis of randomized trial data. SETTING & PARTICIPANTS: 1,970 patients with HFrEF enrolled in PARADIGM-HF with available baseline cysC and Scr measurements. EXPOSURE: Intraindividual differences between eGFR based on cysC (eGFRcysC) and Scr (eGFRScr; eGFRdiffcysC-Scr). OUTCOMES: Clinical outcomes included the PARADIGM-HF primary end point (composite of cardiovascular [CV] mortality or HF hospitalization), CV mortality, all-cause mortality, and worsening kidney function. We also examined poor health-related quality of life (HRQoL), frailty, and worsening HF (WHF), defined as HF hospitalization, emergency department visit, or outpatient intensification of therapy between baseline and 8-month follow-up. ANALYTICAL APPROACH: Fine-Gray subdistribution hazard models and Cox proportional hazards models were used to regress clinical outcomes on baseline eGFRdiffcysC-Scr. Logistic regression was used to investigate the association of baseline eGFRdiffcysC-Scr with poor HRQoL and frailty. Linear regression models were used to assess the association of WHF with eGFRcysC, eGFRScr, and eGFRdiffcysC-Scr at 8-month follow-up. RESULTS: Baseline eGFRdiffcysC-Scr was higher than +10 and lower than-10mL/min/1.73m2 in 13.0% and 35.7% of patients, respectively. More negative values of eGFRdiffcysC-Scr were associated with worse outcomes ([sub]hazard ratio per standard deviation: PARADIGM-HF primary end point, 1.18; P=0.008; CV mortality, 1.34; P=0.001; all-cause mortality, 1.39; P<0.001; worsening kidney function, 1.31; P=0.05). For a 1-standard-deviation decrease in eGFRdiffcysC-Scr, the prevalences of poor HRQoL and frailty increased by 29% and 17%, respectively (P≤0.008). WHF was associated with a more pronounced decrease in eGFRcysC than in eGFRScr, resulting in a change in 8-month eGFRdiffcysC-Scr of-4.67mL/min/1.73m2 (P<0.001). LIMITATIONS: Lack of gold-standard assessment of kidney function. CONCLUSIONS: In patients with HFrEF, discrepancies between eGFRcysC and eGFRScr are common and are associated with clinical outcomes, HRQoL, and frailty. The decline in kidney function associated with WHF is more marked when assessed with eGFRcysC than with eGFRScr. PLAIN-LANGUAGE SUMMARY: Kidney function assessment traditionally relies on serum creatinine (Scr) to establish an estimated glomerular filtration rate (eGFR). However, this has been challenged with the introduction of an alternative marker, cystatin C (cysC). Muscle mass and nutritional status have differential effects on eGFR based on cysC (eGFRcysC) and Scr (eGFRScr). Among ambulatory patients with heart failure enrolled in PARADIGM-HF, we investigated the clinical significance of the difference between eGFRcysC and eGFRScr. More negative values (ie, eGFRScr>eGFRcysC) were associated with worse clinical outcomes (including mortality), poor quality of life, and frailty. In patients with progressive heart failure, which is characterized by muscle loss and poor nutritional status, the decline in kidney function was more pronounced when eGFR was estimated using cysC rather than Scr.

Pulsatility and flow patterns across macro- and microcirculatory arteries of continuous-flow left ventricular assist device patients.

BACKGROUND: Reduced arterial pulsatility in continuous-flow left ventricular assist devices (CF-LVAD) patients has been implicated in clinical complications. Consequently, recent improvements in clinical outcomes have been attributed to the "artificial pulse" technology inherent to the HeartMate3 (HM3) LVAD. However, the effect of the "artificial pulse" on arterial flow, transmission of pulsatility into the microcirculation and its association with LVAD pump parameters is not known. METHODS: The local flow oscillation (pulsatility index, PI) of common carotid arteries (CCAs), middle cerebral arteries (MCAs) and central retinal arteries (CRAs-representing the microcirculation) were quantified by 2D-aligned, angle-corrected Doppler ultrasound in 148 participants: healthy controls, n = 32; heart failure (HF), n = 43; HeartMate II (HMII), n = 32; HM3, n = 41. RESULTS: In HM3 patients, 2D-Doppler PI in beats with "artificial pulse" and beats with "continuous-flow" was similar to that of HMII patients across the macro- and microcirculation. Additionally, peak systolic velocity did not differ between HM3 and HMII patients. Transmission of PI into the microcirculation was higher in both HM3 (during the beats with "artificial pulse") and in HMII patients compared with HF patients. LVAD pump speed was inversely associated with microvascular PI in HMII and HM3 (HMII, r2 = 0.51, p < 0.0001; HM3 "continuous-flow," r2 = 0.32, p = 0.0009; HM3 "artificial pulse," r2 = 0.23, p = 0.007), while LVAD pump PI was only associated with microcirculatory PI in HMII patients. CONCLUSIONS: The "artificial pulse" of the HM3 is detectable in the macro- and microcirculation but without creating a significant alteration in PI compared with HMII patients. Increased transmission of pulsatility and the association between pump speed and PI in the microcirculation indicate that the future clinical care of HM3 patients may involve individualized pump settings according to the microcirculatory PI in specific end-organs.

Impact of Age and Sex on Left Ventricular Remodeling in Patients With Aortic Regurgitation.

BACKGROUND: Current guidelines for aortic regurgitation (AR) recommend the same linear left ventricular (LV) dimension for intervention regardless of age and sex. OBJECTIVES: The purpose of this study was to evaluate the impact of age and sex on the degree of LV remodeling and outcomes. METHODS: We included consecutive patients with severe AR who were serially monitored by echocardiogram between 2010 and 2016. The 2 main endpoints were as follows: 1) LV end-systolic volume indexed to body surface area (LVESVi) and LV end-diastolic volume indexed to body surface area; and 2) adverse events (AE). We evaluated the longitudinal rate of LV remodeling and determined the association between LV volume and AE by age and sex. RESULTS: A total of 525 adult patients (26% women) with a median echocardiogram follow-up of 2.0 years (IQR: 1.0-3.6 years) were included. At baseline, older patients (age ≥60 years) had smaller LV volumes compared with younger patients (age <60 years), eg, the mean LVESVi was 27.3 mL/m2 vs 32.3 mL/m2, respectively. Similarly, women had smaller LV volumes compared with men (mean LVESVi was 23.3 mL/m2 vs 32.4 mL/m2). On serial evaluation, older patients and women maintained smaller LV volumes compared with younger patients and men, respectively. There were 210 (40%) AE during follow-up. The optimal discriminatory threshold for AE varies by age and sex, eg, the LVESVi threshold was highest for young men (50 mL/m2), intermediate for older men (35 mL/m2), and lowest for women (27 mL/m2). CONCLUSIONS: On serial evaluation, older patients and women with chronic AR maintained smaller LV volumes than younger patients and men, respectively, and develop AE at lower LV volumes.