Social Connectedness as a Determinant of Health in African-American Low-Income Families with Young Children: A Cross-Sectional Cohort Study.

OBJECTIVE: This cross-sectional study aimed to assess the level of social connectedness (SC) in African-American low-income families with young children attending a pediatric primary care clinic and examine its relationships with food insecurity and parental well-being. METHODS: This cross-sectional analysis used data from the Healthy Children and Families program, a cohort intervention study addressing food insecurity, conducted by an urban pediatric clinic serving low-income predominantly African-American families. Twenty-seven families completed baseline screening tools, including the Social Provisions Scale five-question short form (SPS-5) to measure SC, a modified version of the United States Department of Agriculture (USDA) Household Food Security Survey Module six-item short form to assess food insecurity, and the Parental Stress Index Short Form to measure parental stress. Descriptive statistics, correlations, and partial correlations were conducted to analyze the data. RESULTS: The average SPS-5 composite score was 14.5 on a scale of 5 to 20. Moderate negative correlations were identified between SC and food insecurity, weaker when controlled for parental stress. Strong negative correlations were identified between SC and parental stress that held when controlled for food insecurity. CONCLUSION: In this study, we propose a conceptual framework highlighting the complex interplay of social connectedness with other social determinants of child health. The findings align with the 2023 Surgeon General's Advisory on the epidemic on the healing effects of social connection and provide insight into the value of incorporating SC assessments into routine screenings in pediatric primary care settings. Further research is needed to explore causal relationships and evaluate the effectiveness of interventions designed to enhance SC in diverse populations.

Comparing Impact of Overactive Bladder Therapies on Nocturia.

IMPORTANCE: Nocturia is a significant symptom in overactive bladder with little data regarding the impact of overactive bladder treatments on nocturia. OBJECTIVES: Compare the effect of anticholinergic (AC) medication, onabotulinum toxin A (BTX), and sacral neuromodulation (SNM) on nocturia. STUDY DESIGN: Secondary analysis of the ABC and ROSETTA trials using data from the National Institutes of Health Data and Specimen Hub database. Patients reporting mean ≥2 voids/night on 3-day diary were included and divided into cohorts by treatment: the ABC trial: (1) AC and (2) BTX 100 units, and the ROSETTA trial: (3) BTX 200 units and (4) SNM. Primary outcome was change in mean voids/night on 3-day diary from baseline to 6 months assessed by mixed-effects models for repeated-measures data with interaction between treatment cohort and time included in model. RESULTS: A total of 197 patients were included: 43 (22%) AC, 37 (19%) BTX 100 U, 63 (32%) BTX 200 U, and 54 (27%) SNM. There were no significant differences in baseline voids/night, demographics, or urodynamic values except for younger age in AC and BTX 100 U cohorts (P = 0.04). At 6 months, all cohorts demonstrated a mean 41% decrease in mean voids/night (2.7 ± 0.4 at baseline to 1.6 ± 0.5 at 6 months; P < 0.001), with no significant difference in change in mean voids/night between treatment cohorts (decrease of 44% in AC, 46% in 100 U BTX, 32% 200 in U BTX, and 33% in SNM; P > 0.05). CONCLUSION: For women with nocturia ≥2/night, treatment with AC, BTX 100 or 200 units, or SNM led to a significant decrease in voids/night at 6 months.

Cost of Cardiovascular Disease Event and Cardiovascular Disease Treatment-Related Complication Hospitalizations in the United States.

BACKGROUND: Cardiovascular disease (CVD) is among the costliest conditions in the United States, and cost-effectiveness analyses can be used to assess economic impact and prioritize CVD treatments. We aimed to develop standardized, nationally representative CVD events and selected possible CVD treatment-related complication hospitalization costs for use in cost-effectiveness analyses. METHODS: Nationally representative costs were derived using publicly available inpatient hospital discharge data from the 2012-2018 National Inpatient Sample. Events were identified using the principal International Classification of Diseases, Ninth Revision and International Classification of Diseases, Tenth Revision codes. Facility charges were converted to costs using charge-to-cost ratios, and total costs were estimated by applying a published professional fee ratio. All costs are reported in 2021 US dollars. Mean costs were estimated for events overall and stratified by age, sex, and survival status at discharge. Annual costs to the US health care system were estimated by multiplying the mean annual number of events by the mean total cost per discharge. RESULTS: The annual mean number of hospital discharges among CVD events was the highest for heart failure (1 087 000 per year) and cerebrovascular disease (800 600 per year). The mean cost per hospital discharge was the highest for peripheral vascular disease ($33 700 [95% CI, $33 300-$34 000]) and ventricular tachycardia/ventricular fibrillation ($32 500 [95% CI, $32 100-$32 900]). Hospitalizations contributing the most to annual US health care costs were heart failure ($19 500 [95% CI, $19 300-$19 800] million) and acute myocardial infarction ($18 300, [95% CI, $18 200-$18 500] million). Acute kidney injury was the most frequent possible treatment complication (515 000 per year), and bradycardia had the highest mean hospitalization costs ($17 400 [95% CI, $17 200-$17 500]). CONCLUSIONS: The hospitalization cost estimates and statistical code reported in the current study have the potential to increase transparency and comparability of cost-effectiveness analyses for CVD in the United States.

Cost-Effectiveness of Icosapent Ethyl in REDUCE-IT USA: Results From Patients Randomized in the United States.

BACKGROUND: In 3146 REDUCE-IT USA (Reduction of Cardiovascular Events With Icosapent Ethyl Intervention Trial USA) participants, icosapent ethyl (IPE) reduced first and total cardiovascular events by 31% and 36%, respectively, over 4.9 years of follow-up. METHODS AND RESULTS: We used participant-level data from REDUCE-IT USA, 2021 US costs, and IPE costs ranging from $4.59 to $11.48 per day, allowing us to examine a range of possible medication costs. The in-trial analysis was participant-level, whereas the lifetime analysis used a Markov model. Both analyses considered value from a US health sector perspective. The incremental cost-effectiveness ratio (incremental costs divided by incremental quality-adjusted life-years) of IPE compared with standard care (SC) was the primary outcome measure. There was incremental gain in quality-adjusted life-years with IPE compared with SC using in-trial (3.28 versus 3.13) and lifetime (10.36 versus 9.83) horizons. Using an IPE cost of $4.59 per day, health care costs were lower with IPE compared with SC for both in-trial ($29 420 versus $30 947) and lifetime ($216 243 versus $219 212) analyses. IPE versus SC was a dominant strategy in trial and over the lifetime, with 99.7% lifetime probability of an incremental cost-effectiveness ratio <$50 000 per quality-adjusted life-year gained. At a medication cost of $11.48 per day, the cost per quality-adjusted life-year gained was $36 208 in trial and $9582 over the lifetime. CONCLUSIONS: In this analysis, at $4.59 per day, IPE offers better outcomes than SC at lower costs in trial and over a lifetime and is cost-effective at $11.48 per day for conventional willingness-to-pay thresholds. Treatment with IPE should be strongly considered in US patients like those enrolled in REDUCE-IT USA. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01492361.

The effect of 12-month postoperative weight change on outcomes following midurethral sling for stress urinary incontinence: a secondary analysis of the ESTEEM and TOMUS randomized trials.

INTRODUCTION AND HYPOTHESIS: Prior studies demonstrate mixed results on the impact of obesity on the success of midurethral slings (MUS), with little known about how postoperative weight change affects outcomes. We aimed to examine the effect of postoperative weight change on outcomes 12 months after MUS for stress urinary incontinence (SUI). METHODS: This secondary analysis utilized data from two multicenter randomized trials of women undergoing MUS placement. Subjects were categorized into cohorts based on change in body weight at 12 months postoperatively: weight gain (≥5% increase); weight loss (≥5% decrease), and weight stable (<5% change). The primary outcome was SUI cure (no SUI episodes in a 3-day bladder diary). Patients with mixed urinary incontinence (MUI) were analyzed for changes in daily average urge incontinence (UUI) episodes in a 3-day diary. Penalized logistic regression assessed the impact of demographic and perioperative variables on the primary outcome. RESULTS: Of the 918 women included, 635 (70%) were weight stable, 144 (15%) had weight gain, and 139 (15%) had weight loss. Patients in the weight loss cohort had a higher smoking rate and a higher baseline body mass index (SD 0.29, 2.7 respectively). All cohorts experienced high SUI cure rates ranging from 77 to 81%, with no significant difference in SUI cure between cohorts (p = 0.607). Of 372 subjects with MUI, the weight loss cohort had significantly greater improvement in UUI episodes. CONCLUSIONS: Weight change at 12 months postoperatively did not significantly alter efficacy of MUS for treatment of SUI. Patients with MUI who lost ≥5% body weight had significantly greater improvement in UUI episodes.

3-Dimensional Strain Analysis of Hypertrophic Cardiomyopathy: Insights From the NHLBI International HCM Registry.

BACKGROUND: Abnormal global longitudinal strain (GLS) has been independently associated with adverse cardiac outcomes in both obstructive and nonobstructive hypertrophic cardiomyopathy. OBJECTIVES: The goal of this study was to understand predictors of abnormal GLS from baseline data from the National Heart, Lung, and Blood Institute (NHLBI) Hypertrophic Cardiomyopathy Registry (HCMR). METHODS: The study evaluated comprehensive 3-dimensional left ventricular myocardial strain from cine cardiac magnetic resonance in 2,311 patients from HCMR using in-house validated feature-tracking software. These data were correlated with other imaging markers, serum biomarkers, and demographic variables. RESULTS: Abnormal median GLS (> -11.0%) was associated with higher left ventricular (LV) mass index (93.8 ± 29.2 g/m2 vs 75.1 ± 19.7 g/m2; P < 0.0001) and maximal wall thickness (21.7 ± 5.2 mm vs 19.3 ± 4.1 mm; P < 0.0001), lower left (62% ± 9% vs 66% ± 7%; P < 0.0001) and right (68% ± 11% vs 69% ± 10%; P < 0.01) ventricular ejection fractions, lower left atrial emptying functions (P < 0.0001 for all), and higher presence and myocardial extent of late gadolinium enhancement (6 SD and visual quantification; P < 0.0001 for both). Elastic net regression showed that adjusted predictors of GLS included female sex, Black race, history of syncope, presence of systolic anterior motion of the mitral valve, reverse curvature and apical morphologies, LV ejection fraction, LV mass index, and both presence/extent of late gadolinium enhancement and baseline N-terminal pro-B-type natriuretic peptide and troponin levels. CONCLUSIONS: Abnormal strain in hypertrophic cardiomyopathy is associated with other imaging and serum biomarkers of increased risk. Further follow-up of the HCMR cohort is needed to understand the independent relationship between LV strain and adverse cardiac outcomes in hypertrophic cardiomyopathy.

An efficient approach for optimizing the cost-effective individualized treatment rule using conditional random forest.

Evidence from observational studies has become increasingly important for supporting healthcare policy making via cost-effectiveness analyses. Similar as in comparative effectiveness studies, health economic evaluations that consider subject-level heterogeneity produce individualized treatment rules that are often more cost-effective than one-size-fits-all treatment. Thus, it is of great interest to develop statistical tools for learning such a cost-effective individualized treatment rule under the causal inference framework that allows proper handling of potential confounding and can be applied to both trials and observational studies. In this paper, we use the concept of net-monetary-benefit to assess the trade-off between health benefits and related costs. We estimate cost-effective individualized treatment rule as a function of patients' characteristics that, when implemented, optimizes the allocation of limited healthcare resources by maximizing health gains while minimizing treatment-related costs. We employ the conditional random forest approach and identify the optimal cost-effective individualized treatment rule using net-monetary-benefit-based classification algorithms, where two partitioned estimators are proposed for the subject-specific weights to effectively incorporate information from censored individuals. We conduct simulation studies to evaluate the performance of our proposals. We apply our top-performing algorithm to the NIH-funded Systolic Blood Pressure Intervention Trial to illustrate the cost-effectiveness gains of assigning customized intensive blood pressure therapy.

Preoperative Patient-Reported Data Indicate the Risk of Prolonged Opioid Use After Hand and Upper Extremity Surgeries.

PURPOSE: Opioids play an important role in pain management after surgery but also increase the risk of prolonged opioid use in patients. The identification of patients who are more likely to use opioids after intended short-term treatment is critical for employing alternative management approaches or targeted interventions for the prevention of opioid-related problems. We used patient-reported data (PRD) and electronic health record information to identify factors predictive of prolonged opioid use after surgery. METHODS: We used our institutional registry containing data on all patients who underwent elective upper extremity surgeries. We evaluated factors associated with prolonged opioid use in the cohort from the year 2018 to 2019. We then validated our results using the 2020 cohort. The predictive variables included preoperative PRD and electronic health record data. Opioid use was determined based on patient reports and/or filled opioid prescriptions 3 months after surgery. We conducted bivariate regression, followed by multivariable regression analyses, and model validation using area under the receiver operating curve. RESULTS: We included 2,114 patients. In our final model on the 2018-2019 electronic health records and PRD data (n = 1,589), including numerous patient-reported outcome questionnaire scores, patients who were underweight and had undergone trauma-related surgery had higher odds of being on opioids at 3 months. Additionally, each 5-unit decrease in the preoperative Patient-Reported Outcomes Measurement Information System Global Physical Health score was associated with a 30% increased odds of being on opioids at 3 months. The area under the receiver operating curve of our model was 70.4%. On validation using data from the 2020 cohort, the area under the receiver operating curve was 60.3%. The Hosmer-Lemeshow test indicated a good fit. CONCLUSIONS: We found that preoperative questionnaire scores were associated with prolonged postoperative opioid use, independent of other variables. Furthermore, PRD may provide unique patient-level insights, alongside other factors, to improve our understanding of postsurgical pain management. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic II.

Perceived symptoms as the primary indicators for 30-day heart failure readmission.

BACKGROUND: To identify 30-day rehospitalizations in patients discharged with heart failure (HF) based on clinical indications, physiologic measures and symptoms. METHODS: Fifty-six patients with heart failure participated. After discharge to home, clinical indicators of dyspnea, fatigue, orthopnea, dyspnea with exertion, daily weight, edema, heart rate, blood pressure, mental condition, medication adherence, and overall well-being were reported by participants daily for up to 30 days. RESULTS: Joint modeling of longitudinal and time-to-event approach was applied to assess the association of readmission with longitudinal measurements. There was no association between demographic, physiological, or laboratory variables and re-hospitalization within 30 days post discharge. Perceptions of dyspnea (p = .012) and feeling unwell (p < .001) were associated with rehospitalization. Patients struggling to breath were 10.7 times more likely to be readmitted than those not struggling to breath. CONCLUSION: Perceived measures, particularly dyspnea and feeling unwell were more important factors than demographic, physiological, or laboratory parameters in predicting 30-day rehospitalizations in this racially diverse cohort. The symptomatic experience of heart failure is an important indicator of rehospitalization.

Safety gaps in medical team communication: Closing the loop on quality improvement efforts in the cardiac catheterization lab.

Closed-loop communication (CLC) is a fundamental aspect of effective communication, critical in the cardiac catheterization laboratory (cath lab) where physician orders are verbal. Complete CLC is typically a hospital and national mandate. Deficiencies in CLC have been shown to impair quality of care. Single center observational study, CLC for physician verbal orders in the cath lab were assessed by direct observation during a 5-year quality improvement effort. Performance feedback and educational efforts were used over this time frame to improve CLC, and the effects of each intervention assessed. Responses to verbal orders were characterized as complete (all important parameters of the order repeated, the mandated response), partial, acknowledgment only, or no response. During the first observational period of 101 cases, complete CLC occurred in 195 of 515 (38%) medication orders and 136 of 235 (50%) equipment orders. Complete CLC improved over time with various educational efforts, (p < 0.001) but in the final observation period of 117 cases, complete CLC occurred in just 259 of 328 (79%) medication orders and 439 of 581 (76%) equipment orders. Incomplete CLC was associated with medication and equipment errors. CLC of physician verbal orders was used suboptimally in this medical team setting. Baseline data indicate that physicians and staff have normalized weak, unreliable communication methods. Such lapses were associated with errors in order implementation. A subsequent 5-year quality improvement program resulted in improvement but a sizable minority of unacceptable responses. This represents an opportunity to improve patient safety in cath labs.

Cost-effectiveness of Icosapent Ethyl for High-risk Patients With Hypertriglyceridemia Despite Statin Treatment.

Importance: The Reduction of Cardiovascular Events With Icosapent Ethyl-Intervention Trial (REDUCE-IT) demonstrated the efficacy of icosapent ethyl (IPE) for high-risk patients with hypertriglyceridemia and known cardiovascular disease or diabetes and at least 1 other risk factor who were treated with statins. Objective: To estimate the cost-effectiveness of IPE compared with standard care for high-risk patients with hypertriglyceridemia despite statin treatment. Design, Setting, and Participants: An in-trial cost-effectiveness analysis was performed using patient-level study data from REDUCE-IT, and a lifetime analysis was performed using a microsimulation model and data from published literature. The study included 8179 patients with hypertriglyceridemia despite stable statin therapy recruited between November 21, 2011, and May 31, 2018. Analyses were performed from a US health care sector perspective. Statistical analysis was performed from March 1, 2018, to October 31, 2021. Interventions: Patients were randomly assigned to IPE, 4 g/d, or placebo and were followed up for a median of 4.9 years (IQR, 3.5-5.3 years). The cost of IPE was $4.16 per day after rebates using SSR Health net cost (SSR cost) and $9.28 per day with wholesale acquisition cost (WAC). Main Outcomes and Measures: Main outcomes were incremental quality-adjusted life-years (QALYs), total direct health care costs (2019 US dollars), and cost-effectiveness. Results: A total of 4089 patients (2927 men [71.6%]; median age, 64.0 years [IQR, 57.0-69.0 years]) were randomly assigned to receive IPE, and 4090 patients (2895 men [70.8%]; median age, 64.0 years [IQR, 57.0-69.0 years]) were randomly assigned to receive standard care. Treatment with IPE yielded more QALYs than standard care both in trial (3.34 vs 3.27; mean difference, 0.07 [95% CI, 0.01-0.12]) and over a lifetime projection (10.59 vs 10.35; mean difference, 0.24 [95% CI, 0.15-0.33]). In-trial, total health care costs were higher with IPE using either SSR cost ($18 786) or WAC ($24 544) than with standard care ($17 273; mean difference from SSR cost, $1513 [95% CI, $155-$2870]; mean difference from WAC, $7271 [95% CI, $5911-$8630]). Icosapent ethyl cost $22 311 per QALY gained using SSR cost and $107 218 per QALY gained using WAC. Over a lifetime, IPE was projected to be cost saving when using SSR cost ($195 276) compared with standard care ($197 064; mean difference, -$1788 [95% CI, -$9735 to $6159]) but to have higher costs when using WAC ($202 830) compared with standard care (mean difference, $5766 [95% CI, $1094-$10 438]). Compared with standard care, IPE had a 58.4% lifetime probability of costing less and being more effective when using SSR cost and an 89.4% probability of costing less than $50 000 per QALY gained when using SSR cost and a 72.5% probability of costing less than $50 000 per QALY gained when using WAC. Conclusions and Relevance: This study suggests that, both in-trial and over the lifetime, IPE offers better cardiovascular outcomes than standard care in REDUCE-IT participants at common willingness-to-pay thresholds.

Characteristics and Outcomes of Patients with Inflammatory Cardiomyopathies Receiving Mechanical Circulatory Support: An STS-INTERMACS Registry Analysis.

BACKGROUND: Durable mechanical circulatory support (MCS) therapy improves survival in patients with advanced heart failure. Knowledge regarding the outcomes experienced by patients with inflammatory cardiomyopathy (CM) who receive durable MCS therapy is limited. METHODS AND RESULTS: We compared patients with inflammatory CM with patients with idiopathic dilated CM enrolled in the STS-INTERMACS registry. Among 19,012 patients, 329 (1.7%) had inflammatory CM and 5978 had idiopathic dilated CM (31.4%). The patients with inflammatory CM were younger, more likely to be White, and women. These patients experienced more preoperative arrhythmias and higher use of temporary MCS. Patients with inflammatory CM had a higher rate of early adverse events (<3 months after device implant), including bleeding, arrhythmias, non-device-related infections, neurologic dysfunction, and respiratory failure. The rate of late adverse events (≥3 months) was similar in the 2 groups. Patients with inflammatory CM had a similar 1-year (80% vs 84%) and 2-year (72% vs 76%, P = .15) survival. Myocardial recovery resulting in device explant was more common among patients with inflammatory CM (5.5% vs 2.3%, P < .001). CONCLUSIONS: Patients with inflammatory CM who received durable MCS appear to have a similar survival compared with patients with idiopathic dilated CM despite a higher early adverse event burden. Our findings support the use of durable MCS in an inflammatory CM population.

Predictors of Major Atrial Fibrillation Endpoints in the National Heart, Lung, and Blood Institute HCMR.

OBJECTIVES: This study sought to identify predictors of major clinically important atrial fibrillation endpoints in hypertrophic cardiomyopathy. BACKGROUND: Atrial fibrillation (AF) is a common morbidity associated with hypertrophic cardiomyopathy (HCM). The HCMR (Hypertrophic Cardiomyopathy Registry) trial is a prospective natural history study of 2,755 patients with HCM with comprehensive phenotyping. METHODS: All patients received yearly telephone follow-up. Major AF endpoints were defined as requiring electrical cardioversion, catheter ablation, hospitalization for >24 h, or clinical decisions to accept permanent AF. Penalized regression via elastic-net methodology identified the most important predictors of major AF endpoints from 46 variables. This was applied to 10 datasets, and the variables were ranked. Predictors that appeared in all 10 sets were then used in a Cox model for competing risks and analyzed as time to first event. RESULTS: Data from 2,631 (95.5%) patients were available for analysis after exclusions. A total of 127 major AF endpoints events occurred in 96 patients over 33.3 ± 12.4 months. In the final model, age, body mass index (BMI), left atrial (LA) volume index, LA contractile percent (active contraction), moderate or severe mitral regurgitation (MR), and history of arrhythmia the most important. BMI, LA volume index, and LA contractile percent were age-dependent. Obesity was a stronger risk factor in younger patients. Increased LA volume, reduced LA contractile percent, and moderate or severe MR put middle-aged and older adult patients at increased risk. CONCLUSIONS: The major predictors of major AF endpoints in HCM include older age, high BMI, moderate or severe MR, history of arrhythmia, increased LA volume, and reduced LA contractile percent. Prospective testing of a risk score based on these parameters may be warranted.

Estimating Systolic Blood Pressure Intervention Trial Participant Posttrial Survival Using Pooled Epidemiologic Cohort Data.

Background Intensive systolic blood pressure treatment (<120 mm Hg) in SPRINT (Systolic Blood Pressure Intervention Trial) improved survival compared with standard treatment (<140 mm Hg) over a median follow-up of 3.3 years. We projected life expectancy after observed follow-up in SPRINT using SPRINT-eligible participants in the NHLBI-PCS (National Heart, Lung, and Blood Institute Pooled Cohorts Study). Methods and Results We used propensity scores to weight SPRINT-eligible NHLBI-PCS participants to resemble SPRINT participants. In SPRINT participants, we estimated in-trial survival (<4 years) using a time-based flexible parametric survival model. In SPRINT-eligible NHLBI-PCS participants, we estimated posttrial survival (≥4 years) using an age-based flexible parametric survival model and applied the formula to SPRINT participants to predict posttrial survival. We projected overall life expectancy for each SPRINT participant and compared it to parametric regression (eg, Gompertz) projections based on SPRINT data alone. We included 8584 SPRINT and 10 593 SPRINT-eligible NHLBI-PCS participants. After propensity weighting, mean (SD) age was 67.9 (9.4) and 68.2 (8.8) years, and 35.5% and 37.6% were women in SPRINT and NHLBI-PCS, respectively. Using the NHLBI-PCS-based method, projected mean life expectancy from randomization was 21.0 (7.4) years with intensive and 19.1 (7.2) years with standard treatment. Using the Gompertz regression, life expectancy was 11.2 (2.3) years with intensive and 10.5 (2.2) years with standard treatment. Conclusions Combining SPRINT and NHLBI-PCS observed data likely offers a more realistic estimate of life expectancy than parametrically extrapolating SPRINT data alone. These results offer insight into the potential long-term effectiveness of intensive SBP goals.

Patient Selection for Intensive Blood Pressure Management Based on Benefit and Adverse Events.

BACKGROUND: Intensive systolic blood pressure (SBP) treatment prevents cardiovascular disease (CVD) events in patients with high CVD risk on average, though benefits likely vary among patients. OBJECTIVES: The aim of this study was to predict the magnitude of benefit (reduced CVD and all-cause mortality risk) along with adverse event (AE) risk from intensive versus standard SBP treatment. METHODS: This was a secondary analysis of SPRINT (Systolic Blood Pressure Intervention Trial). Separate benefit outcomes were the first occurrence of: 1) a CVD composite of acute myocardial infarction or other acute coronary syndrome, stroke, heart failure, or CVD death; and 2) all-cause mortality. Treatment-related AEs of interest included hypotension, syncope, bradycardia, electrolyte abnormalities, injurious falls, and acute kidney injury. Modified elastic net Cox regression was used to predict absolute risk for each outcome and absolute risk differences on the basis of 36 baseline variables available at the point of care with intensive versus standard treatment. RESULTS: Among 8,828 SPRINT participants (mean age 67.9 years, 35% women), 600 CVD composite events, 363 all-cause deaths, and 481 treatment-related AEs occurred over a median follow-up period of 3.26 years. Individual participant risks were predicted for the CVD composite (C index = 0.71), all-cause mortality (C index = 0.75), and treatment-related AEs (C index = 0.69). Higher baseline CVD risk was associated with greater benefit (i.e., larger absolute CVD risk reduction). Predicted CVD benefit and predicted increased treatment-related AE risk were correlated (Spearman correlation coefficient = -0.72), and 95% of participants who fell into the highest tertile of predicted benefit also had high or moderate predicted increases in treatment-related AE risk. Few were predicted as high benefit with low AE risk (1.8%) or low benefit with high AE risk (1.5%). Similar results were obtained for all-cause mortality. CONCLUSIONS: SPRINT participants with higher baseline predicted CVD risk gained greater absolute benefit from intensive treatment. Participants with high predicted benefit were also most likely to experience treatment-related AEs, but AEs were generally mild and transient. Patients should be prioritized for intensive SBP treatment on the basis of higher predicted benefit. (Systolic Blood Pressure Intervention Trial [SPRINT]; NCT01206062).

Comparison of plaque distribution and wire-free functional assessment in patients with stable angina and non-ST elevation myocardial infarction: an optical coherence tomography and quantitative flow ratio study.

BACKGROUND: Data comparing plaque characteristics and wire-free physiological assessment in the target vessel in patients with stable angina versus acute coronary syndrome are sparse. Therefore, we investigated the difference in plaque distribution between stable angina and non-ST-elevation myocardial infarction (NSTEMI) and explored the relationship between target vessel vulnerability by optical coherence tomography (OCT) and wire-free functional assessment with quantitative flow ratio (QFR). METHODS: Patients with stable angina (n = 25) and NSTEMI (n = 24) were in the final prospective study cohort from the DECODE study (ClinicalTrials.gov, NCT02335086). All 5480 OCT frames in the region of interest were analyzed to study plaque morphology in the target vessel. QFR was analyzed from baseline coronary angiography before percutaneous coronary intervention. Vulnerable vessel score (VVS) was calculated from each plaque, and vessel QFR was then compared. RESULTS: Out of all frames, thin-cap fibroatheroma was common with NSTEMI compared to stable angina (10.9 versus 6.3%, P < 0.01), while fibrous plaque was more commonly seen with stable angina compared to NSTEMI (19.7 versus 14.4%, P < 0.01). Calcified plaque was similar in both clinical settings (approximately 6%). Regression analysis showed that segments with normal vessel walls were located significantly farther from the other plaque types. Longitudinal distances for plaque-type in NSTEMI were numerically greater than those for stable angina; however, the mean difference was less than 10 mm. The VVS had a significant inverse linear correlation with QFR (r = -0.34, P = 0.009). CONCLUSIONS: The plaque distribution by OCT between stable angina and NSTEMI was similar. Target vessel vulnerability was greater in patients with lower QFR value.

Anatomical Characteristics Associated With Hypoattenuated Leaflet Thickening in Low-Risk Patients Undergoing Transcatheter Aortic Valve Replacement.

BACKGROUND/PURPOSE: This sub-analysis of the prospective Low Risk TAVR (LRT) trial determined anatomical characteristics associated with hypoattenuated leaflet thickening (HALT), which may contribute to early transcatheter heart valve (THV) degeneration. METHODS/MATERIALS: The LRT trial enrolled 200 low-risk patients between February 2016 and February 2018. All subjects underwent baseline and 30-day CT studies, analyzed by an independent core laboratory. Additional measurements, namely THV expansion, eccentricity, depth, and commissural alignment, were made by consensus of three independent readers. HALT was observed only in the Sapien 3 THV, so Evolut valves were excluded from this analysis. RESULTS: In the LRT trial, 177 subjects received Sapien 3 THVs, of whom 167 (94.3%) had interpretable 30-day CTs and were eligible for this analysis. Twenty-six subjects had HALT (15.6%). Baseline characteristics were similar between groups. There was no difference in THV size implanted and baseline aortic-root geometry between groups. In patients who developed HALT, THV implantation depth was shallower than in patients who did not develop HALT (2.6 ± 1.1 mm HALT versus 3.3 ± 1.8 mm no-HALT, p = 0.03). There were more patients in the HALT group with commissural malalignment (40% vs. 28%; p = 0.25), but this did not reach statistical significance. In a univariable regression model, no predetermined variables were shown to independently predict the development of HALT. CONCLUSIONS: This study did not find anatomical or THV implantation characteristics that predicted the development of HALT at 30 days. This study cannot exclude subtle effects or interaction between factors because of the small number of events.

Comparison of Ultrathin, Bioresorbable-Polymer Sirolimus-Eluting Stents and Thin, Durable-Polymer Everolimus-Eluting Stents in Calcified or Small Vessel Lesions.

BACKGROUND: The ultrathin-strut bioresorbable-polymer sirolimus-eluting stent (BP-SES) demonstrated comparable performance to durable-polymer everolimus-eluting stent (DP-EES) in randomized controlled trials. The purpose of this study was to evaluate the performance of a BP-SES compared with a DP-EES in calcified or small vessel lesions, which represent higher risk of restenosis. METHODS: From the pooled BIOFLOW (BIOFLOW-II, IV, and V; BIOTRONIK - A Prospective Randomized Multicenter Study to Assess the Safety and Effectiveness of the Orsiro Sirolimus Eluting Coronary Stent System in the Treatment of Subjects With up to Three De Novo or Restenotic Coronary Artery Lesions ) randomized controlled trials, a total of 1553 BP-SES and 784 DP-EES patients with valid 1-year follow-up data were available. Coronary lesions were assessed for the presence of moderate-to-severe calcification or small vessels (reference vessel diameter, ≤2.75 mm) by core laboratory analysis. One-year clinical outcomes were assessed with or without the lesion subsets between BP-SES and DP-EES. RESULTS: Baseline characteristics were similar between the groups. Among patients with small vessel disease, target lesion failure (8.0% versus 12.4%; P<0.01) and target vessel myocardial infarction (4.2% versus 7.6%; P<0.01) were significantly lower in BP-SES than in DP-EES. No difference in the outcome between the stents was shown in patients with non-small vessel lesions. In patients with calcified lesions, target lesion failure (12.2% versus 6.9%; P=0.056), and cardiac death (1.9% versus 0.3%; P=0.081) were numerically higher in DP-EES than in BP-SES. In the noncalcified lesion analysis, target vessel myocardial infarction in DP-EES was significantly higher than in BP-SES. Stent thrombosis was similar between the stents in both lesion groups. CONCLUSIONS: Among patients with more complex disease representing a higher risk of target lesion failure, the effectiveness of an ultrathin-strut BP-SES compared with a thin-strut DP-EES was maintained through 1 year. Registration: URL: https://www.clinicaltrials.gov. Unique identifiers: NCT01356888, NCT01939249, NCT02389946.

Risk of Mortality with Paclitaxel Drug-Coated Balloon in De Novo Coronary Artery Disease.

A recent meta-analysis showed increased mortality with paclitaxel drug-coated balloons (PCB) in peripheral arterial disease. With the absence of a definitive study evaluating the risk of mortality with PCB in de novo coronary artery disease, we performed a systematic review and critical appraisal of the literature analyzing this risk. In this review, we included 17 trials with a total of 1573 patients. Cardiac mortality was reported in 16 studies and all-cause mortality in 14 studies. Eleven studies had <12 months' follow-up; 6 had ≥12 months' follow-up. None of the studies was powered to evaluate any differences in mortality. The majority of the included studies have a Jadad scale ≤2. Ten of 17 studies had no mortality, 4 had numerically higher mortality with PCB, and 3 had lower or same mortality with PCB, when compared to drug-eluting stents. A standard meta-analysis cannot be performed, as most studies did not report hazard ratios or Kaplan-Meier survival plots on mortality. With the available literature, conclusions cannot be made in identifying the association of mortality with PCB in de novo coronary artery disease. There is an urgent need for well-designed studies with long-term follow-up for PCB in de novo coronary artery disease. A recent meta-analysis showed increased mortality with paclitaxel drug-coated balloon (PCB) in peripheries. No studies to date evaluate the risk of mortality with PCB in de novo coronary artery disease. In this systematic review and critical appraisal of literature, we outline why the risk cannot be elucidated from the available literature. A standard meta-analysis using inverse variance method would be incorrect to use, as mortality is a time-to-event data point, and only 1 out of 17 studies reported a Kaplan-Meier survival plot.