Spertus, John A

BACKGROUND: Recent randomized trials have demonstrated that for patients with severe tricuspid regurgitation (TR), transcatheter tricuspid valve interventions (TTVI) improve patients’ symptoms, function, and quality of life and that the amount of health status improvement correlates with the extent of TR reduction. Defining this relationship in greater detail can potentially provide insight into device selection and patient-specific treatment goals. We therefore sought to better understand the relationship between both baseline TR severity and change in TR after TTVI and the extent of improvement in health status after TTVI. METHODS: As part of the Tri-QOL (Kansas City Cardiomyopathy Questionnaire Validation in Tricuspid Valve Disease) study, data from 11 studies of TTVI devices were transferred to the US Food and Drug Administration to harmonize and anonymize before analysis by an independent center. This secondary, observational analysis used patient-level data from the 6 single-arm studies of patients who underwent TTVI to explore the association of change in KCCQ-OS with TR grade using multivariable models, adjusted for age, sex, chronic lung disease, and baseline KCCQ-OS. The primary model included TR grade at baseline, TR grade at 1 month, and the interaction between the two. RESULTS: Among 1056 patients with ≥severe TR who underwent TTVI, mean age was 79.1±7.1 years, 60.3% were female, and mean baseline Kansas City Cardiomyopathy Questionnaire-overall summary score [KCCQ-OS] was 49.5±22.3. Baseline TR grade was severe in 33.5%, massive in 35.9%, and torrential in 30.6%. One-month after TTVI, TR was none/trace in 21.7%, mild in 27.2%, moderate in 28.1%, and ≥evere in 23.1%, while the mean change in KCCQ-OS was 17.0±21.3 points. In a multivariable model that included TR grade at baseline, TR grade at 1 month, and their interaction, there was a strong association between reduction in TR and improvement in KCCQ-OS, with no consistent evidence of a threshold of TR grade below which there was no further improvement in KCCQ-OS. However, among patients with baseline torrential TR, the extent of health status improvement plateaued for patients achieving moderate or less TR at 1 month (ie, a 3-grade improvement from baseline). CONCLUSIONS: Health status improvement after TTVI was most strongly associated with the degree of TR reduction, although there was minimal additional improvement for most patients beyond a 3-grade reduction in TR. These findings support the goal of achieving mild or less TR with TTVI, although patients with torrential TR at baseline may be well served if moderate TR can be achieved.

BACKGROUND: Validly measuring disease-specific health status is critical in patients with severe tricuspid regurgitation (TR) to quantify the benefit of different interventions. The Kansas City Cardiomyopathy Questionnaire (KCCQ) has been used to assess health status in patients with severe TR, but its content validity in this patient population is unknown, including whether additional questions are needed to supplement the KCCQ. METHODS: Twenty participants with symptomatic severe TR from 2 midwestern clinical sites were interviewed in 2023 using a semistructured guide. The interview guide addressed symptoms, physical and social functioning, and quality of life concepts of the KCCQ, as well as other potential TR symptoms not represented in the KCCQ. Interview transcripts were analyzed using inductive and deductive coding and content analysis, with additional participants recruited until thematic saturation occurred. RESULTS: Mean age of the participants was 80 (41–89), and 75% were female. Shortness of breath and fatigue were reported by virtually all participants (n=20 and n=19, respectively) and had a marked negative impact on their physical and social functioning and quality of life. Lower limb edema was also reported by 10 participants. Although these concepts are captured by the KCCQ, other symptoms were also reported, including appetite loss (n=8) and upper body edema (n=4), but did not seem to markedly affect participants’ function or quality of life. In addition, all participants who experienced these other symptoms reported symptoms that were already captured by the KCCQ. CONCLUSIONS: All participants experienced symptoms captured by the KCCQ, and these symptoms had a substantial impact on their physical and social functioning and quality of life. Although some participants reported additional symptoms not assessed by the KCCQ, their incorporation would only marginally improve content validity. Thus, the current KCCQ appears to be appropriate for capturing the disease-specific health status of patients with severe TR.

Background Differences in quality of life (QoL) after coronary artery bypass grafting (CABG) compared with percutaneous coronary intervention (PCI) are not well characterized. We aimed to compare the short‐ and long‐term effects of CABG versus PCI on QoL. Methods and Results We performed a systematic review and meta‐analysis of randomized controlled trials comparing CABG versus PCI using the Seattle Angina Questionnaire (SAQ)‐Angina Frequency, SAQ‐QoL, SAQ‐Physical Limitations, EuroQoL‐5D, and Short‐Form Questionnaire. We calculated mean changes within each group from baseline to 1, 6, 12, and 36 to 60 months (latest follow‐up) and the weighted mean differences between groups using inverse‐variance methods. A total of 10 760 patients were enrolled in 5 trials. From baseline to 12 months and 36 to 60 months, the mean change in SAQ‐Angina Frequency was >22 points (95% CI, 21.0–25.6) after both PCI and CABG. The mean difference in SAQ‐Angina Frequency was similar between procedures at 1 month and at 36 to 60 months but favored CABG at 12 months (1.97 [95% CI, 0.68–3.26]). SAQ‐QoL favored PCI at 1 month (−2.92 [95% CI, −4.66 to −1.18]) and CABG at 6 (2.50 [95% CI, 1.02–3.97]), 12 (3.30 [95% CI, 1.78–4.82]), and 36 to 60 months (3.17 [95% CI, 0.54 5.80). SAQ‐Physical Limitations (−12.61 [95% CI, −16.16 to −9.06]) and EuroQoL‐5D (−0.07 [95% CI, −0.08 to −0.07) favored PCI at 1 month. Short‐Form Questionnaire‐Physical Component favored CABG at 12 months (1.18 [95% CI, 0.46–1.90]). Conclusions Both PCI and CABG improved long‐term disease‐specific and generic QoL.

ImportanceTafamidis reduced all-cause mortality and cardiovascular-related hospitalizations and minimized patient-reported health status deterioration at 30 months in patients with transthyretin (ATTR) amyloidosis. However, the clinical significance of health status changes remains unclear, particularly in patients with New York Heart Association (NYHA) class III symptoms who experienced more cardiovascular-related hospitalizations than those with NYHA class I-II symptoms.ObjectiveTo evaluate the health status of patients taking tafamidis with baseline NYHA class III symptoms.Design, Setting, and ParticipantsThis randomized clinical trial post hoc analysis evaluated data for patients with transthyretin (ATTR) cardiac amyloidosis and NYHA class I-III symptoms at baseline who were enrolled in ATTR-ACT, a placebo-controlled study of tafamidis held at 48 sites in 13 countries.InterventionsTafamidis meglumine, 80 mg or 20 mg (pooled cohort), vs placebo.Main Outcomes and MeasuresEstablished thresholds for clinical benefit on the Kansas City Cardiomyopathy Questionnaire Overall Summary (KCCQ-OS) were used to define response groups (very large decline to very large improvement); the proportion of patients in each group was calculated within each baseline NYHA class.ResultsAmong 441 patients (264 tafamidis, 177 placebo), the mean (SD) age was 74.3 (7.0) years; 398 (90%) were male and 43 (10%) were female. Mean (SD) baseline KCCQ-OS scores were 67.3 (21.4) in the tafamidis group and 65.9 (21.7) in the placebo group (range: 0-100, with 100 indicating the best health). There was a significant shift toward better KCCQ-OS scores in patients receiving tafamidis (odds ratio for 10-point improvement 2.4; 95% CI, 1.6-3.4; P < .001). More patients taking tafamidis were alive and not worse at all time points (37% vs 15% at month 30). These findings were similar in patients with NYHA class III symptoms. In patients with NYHA class III symptoms alive at 30 months, improvements in health status were more common (35% vs 10%) and declines were less common (38% vs 57%) with tafamidis vs placebo.Conclusions and RelevanceIn ATTR-ACT, although patients with baseline NYHA class III symptoms had worse overall outcomes, treatment with tafamidis yielded better health status compared with placebo.Trial RegistrationClinicalTrials.gov Identifier: NCT01994889

Background: Clinical and anatomical characteristics are often considered key factors in deciding between percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) in patients with complex coronary artery disease (CAD) such as left-main CAD or 3-vessel disease. However, little is known about the interaction between self-reported preprocedural physical/mental health and clinical outcomes after revascularization. Methods: This subgroup analysis of the SYNTAXES trial (SYNTAX Extended Survival), which is the extended follow-up of the randomized SYNTAX trial (Synergy Between PCI With Taxus and Cardiac Surgery) comparing PCI with CABG in patients with left-main CAD or 3-vessel disease, stratified patients by terciles of Physical (PCS) or Mental Component Summary (MCS) scores derived from the preprocedural 36-Item Short Form Health Survey, with higher PCS and MCS scores representing better physical and mental health, respectively. The primary end point was all-cause death at 10 years. Results: A total of 1656 patients with preprocedural 36-Item Short Form Health Survey data were included in the present study. Both higher PCS and MCS were independently associated with lower 10-year mortality (10-point increase in PCS adjusted hazard ratio, 0.84 [95% CI, 0.73–0.97]; P =0.021; in MCS adjusted hazard ratio, 0.85 [95% CI, 0.76–0.95]; P =0.005). A significant survival benefit with CABG over PCI was observed in the highest PCS (>45.5) and MCS (>52.3) terciles with significant treatment-by-subgroup interactions (PCS P interaction =0.033, MCS P interaction =0.015). In patients with both high PCS (>45.5) and MCS (>52.3), 10-year mortality was significantly higher with PCI compared with CABG (30.5% versus 12.2%; hazard ratio, 2.87 [95% CI, 1.55–5.30]; P =0.001), whereas among those with low PCS (≤45.5) or low MCS (≤52.3), there were no significant differences in 10-year mortality between PCI and CABG, resulting in a significant treatment-by-subgroup interaction ( P interaction =0.002). Conclusions: Among patients with left-main CAD or 3-vessel disease, patient-reported preprocedural physical and mental health status was strongly associated with long-term mortality and modified the relative treatment effects of PCI versus CABG. Patients with the best physical and mental health had better 10-year survival with CABG compared with PCI. Assessment of self-reported physical and mental health is important when selecting the optimal revascularization strategy. Registration: URL: https://www.clinicaltrials.gov ; SYNTAXES Unique identifier: NCT03417050. URL: https://www.clinicaltrials.gov ; SYNTAX Unique identifier: NCT00114972.

Background: The Kansas City Cardiomyopathy Questionnaire (KCCQ) has been psychometrically evaluated in multiple heart failure (HF) populations, but the comparability of its psychometric properties between men and women is unknown. Methods: Data from 3 clinical trials (1 in stable HF with preserved ejection fraction, 1 each in stable and acute HF with reduced ejection fraction) and 1 prospective cohort study (stable HF with reduced ejection fraction), incorporating 6773 men and 3612 women with HF, were used to compare the construct validity, internal and test-retest reliability, ability to detect change, predict mortality and hospitalizations and minimally important differences between the 2 sexes. Interactions of the KCCQ overall summary and subdomain scores by sex were independently examined. Results: The KCCQ-Overall Summary score correlated well with New York Heart Association functional class in both sexes across patients with stable (correlation coefficient: −0.40 in men versus −0.49 in women) and acute (−0.37 in men versus −0.34 in women) HF. All KCCQ subdomains demonstrated concordant relationships with relevant comparison standards with no significant interactions by sex in 19 of 21 of these construct validity analyses. All KCCQ scores were equally predictive and other psychometric evaluations showed similar results by sex: test-retest reliability (intraclass correlation coefficient 0.94 in men versus 0.92 in women), responsive to change (standardized response mean 1.01 in both sexes), as were the minimally important differences and internal reliability. Conclusions: The psychometric properties of the KCCQ, in terms of validity, prognosis, reliability, and sensitivity to change, are comparable in men and women with HF with preserved ejection fraction and HF with reduced ejection fraction.

Background: Ischemia with no obstructive coronary artery disease (INOCA) is common and has an adverse prognosis. We set out to describe the natural history of symptoms and ischemia in INOCA. Methods: CIAO-ISCHEMIA (Changes in Ischemia and Angina over One Year in ISCHEMIA Trial Screen Failures With INOCA) was an international cohort study conducted from 2014 to 2019 involving angina assessments (Seattle Angina Questionnaire) and stress echocardiograms 1 year apart. This was an ancillary study that included patients with a history of angina who were not randomly assigned in the ISCHEMIA trial. Stress-induced wall motion abnormalities were determined by an echocardiographic core laboratory blinded to symptoms, coronary artery disease status, and test timing. Medical therapy was at the discretion of treating physicians. The primary outcome was the correlation between the changes in the Seattle Angina Questionnaire angina frequency score and changes in echocardiographic ischemia. We also analyzed predictors of 1-year changes in both angina and ischemia, and we compared CIAO participants with ISCHEMIA participants with obstructive coronary artery disease who had stress echocardiography before enrollment, as CIAO participants did. Results: INOCA participants in CIAO were more often female (66% of 208 versus 26% of 865 ISCHEMIA participants with obstructive coronary artery disease, P <0.001), but the magnitude of ischemia was similar (median 4 ischemic segments [interquartile range, 3–5] both groups). Ischemia and angina were not significantly correlated at enrollment in CIAO ( P =0.46) or ISCHEMIA stress echocardiography participants ( P =0.35). At 1 year, the stress echocardiogram was normal in half of CIAO participants, and 23% had moderate or severe ischemia (≥3 ischemic segments). Angina improved in 43% and worsened in 14%. Change in ischemia over 1 year was not significantly correlated with change in angina (ρ=0.029). Conclusions: Improvement in ischemia and angina were common in INOCA but not correlated. Our INOCA cohort had a degree of inducible wall motion abnormalities similar to concurrently enrolled ISCHEMIA participants with obstructive coronary artery disease. Our results highlight the complex nature of INOCA pathophysiology and the multifactorial nature of angina. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02347215.

Abstract Aims To assess gender differences in in-hospital mortality and 90-day readmission rates among patients undergoing transcatheter aortic valve replacement (TAVR) in the USA. Methods and results Hospitalizations for TAVR were retrospectively identified in the National readmissions database (NRD) from 2012 to 2017. Gender based differences in in-hospital mortality and 90-day readmissions were explored using multivariable logistic regression models. During the study period, an estimated 171 361 hospitalizations for TAVR were identified, including 79 722 (46.5%) procedures in women and 91 639 (53.5%) in men. Unadjusted in-hospital mortality and 90-day all-cause readmissions were significantly higher for women compared with men (2.7% vs. 2.3%, P = 0.002; 25.1% vs. 24.1%, P = 0.012, respectively). After adjusting for baseline characteristics, women had 13% greater adjusted odds of in-hospital mortality [adjusted odds ratio (aOR): 1.13, 95% confidence interval (CI): 1.02–1.26, P = 0.017], and 9% greater adjusted odds of 90-day readmission compared with men (aOR: 1.09, 95% CI: 1.05–1.14, P &lt; 0.001). During the study period, there was a steady decrease in-hospital mortality (5.3% in 2012 to 1.6% in 2017; Ptrend &lt; 0.001) and 90-day (29.9% in 2012 to 21.7% in 2017; Ptrend &lt; 0.001) readmission rate in both genders. Conclusion In-hospital mortality and readmission rates for TAVR hospitalizations have decreased over time across both genders. Despite these improvements, women undergoing TAVR continue to have a modestly higher in-hospital mortality, and 90-day readmission rates compared with men. Given the expanding indications and use of TAVR, further research is necessary to identify the reasons for this persistent gap and design appropriate interventions.

The interrelationships between atrial fibrillation (AF) and heart failure (HF) are complex and poorly understood, yet the number of patients with AF and HF continues to increase worldwide. Thus, there is a need for initiatives that prioritize research on the intersection between AF and HF. This article summarizes the proceedings of a virtual workshop convened by the US National Heart, Lung, and Blood Institute to identify important research opportunities in AF and HF. Key knowledge gaps were reviewed and research priorities were proposed for characterizing the pathophysiological overlap and deleterious interactions between AF and HF; preventing HF in people with AF; preventing AF in individuals with HF; and addressing symptom burden and health status outcomes in AF and HF. These research priorities will hopefully help inform, encourage, and stimulate innovative, cost-efficient, and transformative studies to enhance the outcomes of patients with AF and HF.

Background: The Atrial Fibrillation Effect on Quality-of-Life (AFEQT) questionnaire has recently been validated to measure the impact of atrial fibrillation on quality of life, but a clinically important difference in AFEQT score has not been well defined. Methods and Results: To determine the clinically important difference in overall AFEQT (score range= 0 [worst] to 100 [best]) and selected subscales, we analyzed data in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) registry, a United States-based outpatient atrial fibrillation registry. AFEQT was assessed at baseline and 1 year in a subset of 1347 ORBIT-AF patients from 80 US sites participating in ORBIT-AF from June 2010 to August 2011. The mean change method was used to relate changes in 1-year AFEQT scores to clinically important changes in the physician assessment of European Heart Rhythm Association functional status (1 class improvement and separately 1 class deterioration). Clinically important differences and 95% CI corresponding to either a 1 European Heart Rhythm Association class improvement or deterioration were 5.4 (3.6–7.2) and −4.2 (−6.9 to −1.5) AFEQT points, respectively. Similarly, clinically important difference values were seen for a 1 European Heart Rhythm Association class improvement for the AFEQT subscales Activities of Daily Living and Symptoms: 5.1 (2.5–7.6) and 7.1 (5.3–9.0) AFEQT points, respectively. Conclusions: Based on the anchor of 1 European Heart Rhythm Association class change, changes in AFEQT score of + or −5 points are clinically important changes in patients’ health. Clinical Trial Registration: URL: https://clinicaltrials.gov . Unique identifier: NCT01165710.