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.

ImportanceImproving patients’ health status is a key goal of treating tricuspid regurgitation (TR). The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a heart failure disease-specific health status measure used to capture the health status impact of TR and the benefit of transcatheter tricuspid valve intervention (TTVI), but its validity in this clinical setting is unknown.ObjectiveTo evaluate the psychometric properties of the KCCQ in patients with TR.Design, Setting, and ParticipantsData were pooled from patients with severe TR enrolled in 11 manufacturer-sponsored trials of TTVI. The data were transferred to the US Food and Drug Administration to harmonize and anonymize prior to analysis by an independent center. Data were collected from December 2015 to April 2023, and data analysis was performed from July to October 2023.Main Outcomes and MeasuresPrespecified analyses included evaluation of internal consistency, reproducibility, responsiveness, construct validity, and predictive validity. Outcomes were determined using Cronbach α, score comparisons, intraclass correlation, Cohen d, Spearman correlations with best available reference measures, and association of scores and changes in scores with risk of subsequent clinical events.ResultsThe study cohort was composed of 2693 patients enrolled in either single-arm (n = 1517) or randomized (n = 1176) investigations of TTVI. Mean (SD) patient age was 78.6 (8.0) years, 1658 of 2693 patients (61.6%) were female, and the mean (SD) baseline KCCQ Overall Summary (KCCQ-OS) score was 50 (23). There was strong internal consistency within individual domains (Cronbach α, .77-.83). Among clinically stable patients between 1 and 6 months, there were small mean changes in KCCQ domain and summary scores (differences of −0.1 to 1.9 points), demonstrating reproducibility. In contrast, domain and summary scores of patients who underwent TTVI showed large improvements at 1 month after treatment (mean changes, 12.1-21.4 points), indicating excellent perceived responsiveness. Construct validity was moderately strong when domains were compared with best available reference measures (Spearman correlations, 0.47-0.69). In both cross-sectional and longitudinal analyses, the KCCQ-OS was associated with clinical events, with lower scores associated with an increased risk of mortality (hazard ratio, 1.34 per 10-point decrement; 95% CI, 1.22-1.47) and heart failure hospitalization (hazard ratio, 1.24 per 10-point decrement; 95% CI, 1.17-1.31).Conclusions and RelevanceIn this cohort study, the KCCQ had strong psychometric properties in patients with severe TR, including reliability, responsiveness, and validity. These data support use of the KCCQ in patients with severe TR as a measure of their symptoms, function, and quality of life and also for assessing the impact of interventions, such as TTVI, in rigorously controlled trials.

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.

Abstract Background Pregnancy related cardiomyopathy is a significant cause of maternal morbidity and mortality globally. A presumed overlap between normal pregnancy-associated symptoms and clinical symptoms of cardiomyopathy contributes to delays in diagnosis and increased risk of maternal mortality. Purpose We sought to evaluate the association between patient-reported cardiovascular symptoms and the presence of cardiomyopathy among pregnant and postpartum patients. We hypothesize that individual cardiovascular symptoms are unrelated to the presence of cardiomyopathy. We also evaluated the use of a novel adaptation of a validated health status questionnaire in relation to cardiomyopathy. Methods We enrolled 48 pregnant (>13 weeks) and postpartum (up to 12 months) participants in a prospective study between October 2021 and February 2022. All study participants completed a baseline questionnaire, which included current cardiovascular symptoms, an assessment of health status using an adapted version of the Kansas City Cardiomyopathy Questionnaire (KCCQ-12), followed by a resting transthoracic echocardiogram on the same day. We defined cardiomyopathy as a left ventricular ejection fraction (LVEF) <50% based on 2-D echocardiography. Fisher's exact and Wilcoxon rank-sum tests were employed to evaluate the association between reported cardiovascular symptoms, the adapted KCCQ-12 (KCC-A) score, and cardiomyopathy. Results At the time of enrollment, 67% were pregnant and 33% postpartum. Forty-eight percent identified as White, 31% as Black, 10% as Asian, and 10% as other race. The median age was 31 years (Q1: 28, Q3: 35) and 6% had an LVEF <50%. We found no statistically significant association between four reported cardiovascular symptoms (shortness of breath, orthopnea, fast breathing, and episodes of “asthma” that did not improve with inhalers or other treatment) and cardiomyopathy or medial E/e' ratio. KCC-A scores were low in the study population overall (median 52; Q1:40, Q3: 61). We demonstrated a significantly lower KCC-A score among women with LVEF <50% (median 24; Q1: 15, Q3: 44) compared to women with LVEF ≥50% (median 54; Q1: 44, Q3: 61) p=0.02. Conclusions We showed no significant association between individual cardiovascular symptoms and cardiomyopathy in an obstetric population. However, we demonstrate for the first time that an adapted KCCQ-12 questionnaire for health status assessment could potentially identify women with a high-likelihood of cardiomyopathy during the peripartum period who may benefit from additional evaluation including echocardiography. Larger studies are needed to validate this finding. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): This study was funded by a research grant from the Miami Heart Research Institute, Florida Heart Foundation. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health

Abstract Aims The aim of this study was to investigate the impact on 10-year survival of patient-reported anginal status at 1 year following percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) in patients with left main coronary artery disease (LMCAD) and/or three-vessel CAD (3VD). Methods and results In this post hoc analysis of the randomized SYNTAX Extended Survival study, patients were classified as having residual angina (RA) if their self-reported Seattle Angina Questionnaire angina frequency (SAQ-AF) scale was ≤90 at the 1-year follow-up post-revascularization with PCI or CABG. The primary endpoint of all-cause death at 10 years was compared between the RA and no-RA groups. A sensitivity analysis was performed using a 6-month SAQ-AF. At 1 year, 373 (26.1%) out of 1428 patients reported RA. Whilst RA at 1 year was an independent correlate of repeat revascularization at 5 years [18.3 vs. 11.5%; adjusted hazard ratio (HR): 1.54; 95% confidence interval (CI): 1.10–2.15], it was not associated with all-cause death at 10 years (22.1 vs. 21.6%; adjusted HR: 1.11; 95% CI: 0.83–1.47). These results were consistent when stratified by the modality of revascularization (PCI or CABG) or by anginal frequency. The sensitivity analysis replicating the analyses based on 6-month angina status resulted in similar findings. Conclusion Among patients with LMCAD and/or 3VD, patient-reported RA at 1 year post-revascularization was independently associated with repeat revascularization at 5 years; however, it did not significantly increase 10-year mortality, irrespective of the primary modality of revascularization or severity of RA.

Background: An obesity paradox, with better long-term survival in obese patients undergoing percutaneous coronary intervention (PCI), has been well described. The association between obesity and health status outcomes after PCI is unknown. Methods: We prospectively enrolled 3,281 PCI patients in a 10-center observational cohort study and categorized their body mass index (BMI) into normal (18.5 to <25), overweight (25 to <30), obese (30 to <35) and morbidly obese (≥ 35).Generalized linear models were used to describe the association between BMI and health status measures at 6 & 12 months, after adjusting for baseline characteristics and health status scores. Health status outcomes included; Seattle Angina Questionnaire [SAQ] Angina Frequency (AF), and Quality of Life (QL) scores, as well as the EQ-5D visual analogue scale (EQ-5D VAS). Interaction with time was not significant, so an estimate of the average benefit over time was generated. Results: The distribution of patients’ BMI revealed that 17% were normal, 35% overweight, 28% obese and 20% morbidly obese. Compared with normal weight patients, morbidly obese individuals were younger (mean 60.8 yr vs. 67.9 yr) and had a higher prevalence of diabetes, hypertension and heart failure. They underwent radial artery access (12.0% vs. 7.0%) and drug eluting stent implantation (80.4% vs. 76.0%) more frequently. Unadjusted changes in scores were lower (worse) among morbidly obese as compared with normal weight patients for SAQ AF (mean difference [MD] -1.52; 95% Confidence Interval [CI] -3.05, -0.02), SAQ QL (MD -2.51; CI -4.48, -0.54), and EQ-5D VAS (MD -5.74;CI -7.52, -3.96). After adjustment, these differences were no longer significantly different for SAQ AF and SAQ QL (figure), although EQ-5D VAS scores remained lower among obese and morbidly obese patients. Conclusion: The overall health status was mildly worse among obese and morbidly obese individuals after PCI, but the benefits of PCI on patients’ disease-specific health status were similar across weight categories. This suggests that PCI is equally effective in improving angina and disease-specific quality of life, independent of patients’ weight.

Background: Cardiac rehabilitation (CR) is a class Ia recommendation and endorsed performance measure for the quality of care in acute myocardial infarction (AMI) survivors. While participation in CR after AMI is associated with reduced mortality, conflicting data exists on its association with health status outcomes. Methods: Using data from 2 prospective AMI registries (TRIUMPH and PREMIER), we identified patients for whom baseline and follow-up health status scores and documentation of CR participation (attendance of 1 or more sessions within 6 months post-AMI) were available. Health status was assessed by four Seattle Angina Questionnaire (SAQ) domain scores (quality of life [QoL], angina frequency [AF], treatment satisfaction [TS], and physical limitation [PL]), as well as SF-12 physical and mental health composite scores ( PCS & MCS ). We created propensity matched cohorts of CR participants and non-participants to examine the association between CR participation with health status (6 and 12 months) and all-cause mortality (up to 7 years), using conditional repeated measures and proportional hazards models, respectively. Results: Among 3,957 AMI patients from 31 sites, 2,015 patients (51%) participated in CR after discharge. Compared to non-participants, CR participants were more often Caucasian (83.6% vs. 65.4%), had higher rates of health insurance (90.6% vs. 79.3%), but clinically similar baseline SAQ and SF-12 scores in all domains. After propensity matching, all covariates were well-balanced (Standardized Difference <10 for all patient characteristics) between CR participants and non-participants. In the repeated measures analysis, the mean SAQ and SF-12 domain scores were clinically similar for both groups at 6 and 12 months after hospital discharge (Table). Using a conditional proportional hazards model, a decrease in all-cause mortality was noted in the CR participant group (HR 0.59, 95% CI [0.46, 0.75]). Conclusion: In a large, multi-center AMI cohort, we found that although CR participation seemed to improve survival, CR participants had similar health status improvements after AMI as non-participants. Further investigation is required to identify how CR programs can further maximize the health status benefits to post-AMI participants.