The Promise and Illusion of Continuous, Cuffless Blood Pressure Monitoring.

PURPOSE OF REVIEW: Blood pressure (BP) fluctuations outside of clinic are increasingly recognized for their role in the development of cardiovascular disease, syncope, and premature death and as a promising target for tailored hypertension treatment. However, current cuff-based BP devices, including home and ambulatory devices, are unable to capture the breadth of BP variability across human activities, experiences, and contexts. RECENT FINDINGS: Cuffless, wearable BP devices offer the promise of beat-to-beat, continuous, noninvasive measurement of BP during both awake and sleep periods with minimal patient inconvenience. Importantly, cuffless BP devices can characterize BP variability, allowing for the identification of patient-specific triggers of BP surges in the home environment. Unfortunately, the pace of evidence, regulation, and validation testing has lagged behind the pace of innovation and direct consumer marketing. We provide an overview of the available technologies and devices for cuffless BP monitoring, considerations for the calibration and validation of these devices, and the promise and pitfalls of the cuffless BP paradigm.

Diminished Short-Term Efficacy of Reduced-Dose Induction BCG in the Treatment of Non-Muscle Invasive Bladder Cancer.

The ongoing Bacillus Calmette-Guérin (BCG) shortage has created challenges for the treatment of non-muscle invasive bladder cancer (NMIBCa). Our objective was to evaluate the efficacy of reduced-dose induction BCG (RD-iBCG) compared to full-dose induction BCG (FD-iBCG) regarding recurrence rates. We hypothesized that patients receiving RD-iBCG may recur at a higher rate compared to those who received FD-iBCG therapy. A retrospective review of all patients with NMIBCa treated with intravesical therapy at our institution between 2015-2020 was conducted. Inclusion criteria consisted of having a diagnosis of AUA intermediate or high-risk NMIBCa with an indication for a six-week induction course of FD or RD-BCG with at least 1 year of documented follow up. The data were censored at one year. Propensity score matching for age, sex, tumor pathology, and initial vs. recurrent disease was performed. The primary endpoint was bladder cancer recurrence, reported as recurrence-free survival. A total of 254 patients were reviewed for this study. Our final cohort was 139 patients after exclusion. Thirty-nine percent of patients had HGT1 disease. 38.6% of patients receiving RD-BCG developed a recurrence of bladder cancer within a one-year follow-up as compared to 33.7% of patients receiving FD therapy. After propensity matching, this value remained statistically significant (p = 0.03). In conclusion, RD-iBCG for NMIBCa is associated with a significantly greater risk of recurrence than full-dose induction therapy, suggesting that RD-iBCG may not be equivalent or non-inferior to full-dose administration in the short term.

Mechanical thrombectomy versus catheter directed thrombolysis in patients with pulmonary embolism: A multicenter experience.

OBJECTIVES: Compare in-hospital outcomes of patients treated with either mechanical thrombectomy (MT) or catheter directed lysis (CDL) in treatment of acute pulmonary embolism (PE). METHODS: This is a multicenter, retrospective cohort study of patients undergoing MT or CDL for acute PE between 2014 and 2021. The primary outcome was the composite of in-hospital death, significant bleed, vascular complication, or need for mechanical support post-procedure. Secondary outcomes included the individual components of the composite outcome in addition to blood transfusions, invasive hemodynamics, echocardiographic data, and intensive care unit (ICU) utilization. RESULTS: 458 patients were treated for PE with 266 patients in the CDL arm and 192 patients in the MT arm. The primary composite endpoint was not significantly different between the two groups with CDL 12% versus MT 11% (p = 0.5). There was a significant difference in total length of ICU time required with more in the CDL group versus MT (3.8 ± 2.0 vs. 2.8 ± 3.0 days, p = 0.009). All other secondary end points showed no significant difference between the groups. CONCLUSIONS: In patients undergoing catheter directed treatment of PE, there was no difference between MT and CDL in terms of in-hospital mortality, bleeds, catheter-related complications, and hemodynamics.

Intermediate-Term Outcomes for Patients with Submassive Pulmonary Embolism Treated With Catheter-Directed Thrombolysis.

OBJECTIVE: We aimed to assess the intermediate-term outcomes for patients receiving catheter-directed thrombolysis (CDT) for submassive pulmonary embolism (PE). BACKGROUND: Previous research has shown improvements in right ventricular (RV) function and dilation at 24 hours when CDT was used to treat submassive PE. METHODS: Consecutive patients presenting with submassive PE treated with directed t-PA infusion at a single center were identified and included in this study. Outcomes included cardiovascular mortality, RV function by echocardiogram, 30-day readmission, and major bleeding. RESULTS: The study population was 79 patients with submassive PE; 46% were men, with an average age of 58 years and an average pulmonary embolism severity index (PESI) score of 108. One patient died of cardiovascular causes during the index hospitalization. There were no additional deaths within 30 days of admission. The observed 30-day mortality rate was low compared with that predicted by PESI (1.3% vs 4.0%-11.4%). Fifty-two patients had follow-up echocardiography available for evaluation after CDT. Of these, 62% showed return to normal RV function and size, and 19% demonstrated mild residual RV dysfunction or dilation. Eight patients (10%) had a hospital readmission within 30 days of discharge, including 6 admissions due to cardiopulmonary complications or minor bleeding and 2 for non-cardiopulmonary or bleeding-related reasons. The observed readmission rate of 10% was similar to historic rates of 12.8%. CONCLUSIONS: Intermediate-term follow-up for CDT demonstrates high success rates with low adverse event rates. Further randomized data are needed to study the long-term benefits of CDT.

Multiomic Profiling in Black and White Populations Reveals Novel Candidate Pathways in Left Ventricular Hypertrophy and Incident Heart Failure Specific to Black Adults.

BACKGROUND: Increased left ventricular (LV) mass is associated with adverse cardiovascular events including heart failure (HF). Both increased LV mass and HF disproportionately affect Black individuals. To understand the underlying mechanisms, we undertook a proteomic screen in a Black cohort and compared the findings to results from a White cohort. METHODS: We measured 1305 plasma proteins using the SomaScan platform in 1772 Black participants (mean age, 56 years; 62% women) in JHS (Jackson Heart Study) with LV mass assessed by 2-dimensional echocardiography. Incident HF was assessed in 1600 participants. We then compared protein associations in JHS to those observed in White participants from FHS (Framingham Heart Study; mean age, 54 years; 56% women). RESULTS: In JHS, there were 110 proteins associated with LV mass and 13 proteins associated with incident HF hospitalization with false discovery rate <5% after multivariable adjustment. Several proteins showed expected associations with both LV mass and HF, including NT-proBNP (N-terminal pro-B-type natriuretic peptide; ß=0.04; P=2×10-8; hazard ratio, 1.48; P=0.0001). The strongest association with LV mass was novel: LKHA4 (leukotriene-A4 hydrolase; ß=0.05; P=5×10-15). This association was confirmed on an alternate proteomics platform and further supported by related metabolomic data. Fractalkine/CX3CL1 (C-X3-C Motif Chemokine Ligand 1) showed a novel association with incident HF (hazard ratio, 1.32; P=0.0002). While established biomarkers such as cystatin C and NT-proBNP showed consistent associations in Black and White individuals, LKHA4 and fractalkine were significantly different between the two groups. CONCLUSIONS: We identified several novel biological pathways specific to Black adults hypothesized to contribute to the pathophysiologic cascade of LV hypertrophy and incident HF including LKHA4 and fractalkine.

Association of Dimethylguanidino Valeric Acid With Partial Resistance to Metabolic Health Benefits of Regular Exercise.

Importance: Metabolic responses to exercise training are variable. Metabolite profiling may aid in the clinical assessment of an individual's responsiveness to exercise interventions. Objective: To investigate the association between a novel circulating biomarker of hepatic fat, dimethylguanidino valeric acid (DMGV), and metabolic health traits before and after 20 weeks of endurance exercise training. Design, Setting, and Participants: This study involved cross-sectional and longitudinal analyses of the Health, Risk Factors, Exercise Training, and Genetics (HERITAGE) Family Study, a 20-week, single-arm endurance exercise clinical trial performed in multiple centers between 1993 and 1997. White participants with sedentary lifestyles who were free of cardiometabolic disease were included. Metabolomic tests were performed using a liquid chromatography, tandem mass spectrometry method on plasma samples collected before and after exercise training in the HERITAGE study. Metabolomics and data analysis were performed from August 2017 to May 2018. Exposures: Plasma DMGV levels. Main Outcome and Measures: The association between DMGV levels and measures of body composition, plasma lipids, insulin, and glucose homeostasis before and after exercise training. Results: Among the 439 participants included in analyses from HERITAGE, the mean (SD) age was 36 (15) years, 228 (51.9%) were female, and the median (interquartile range) body mass index was 25 (22-28). Baseline levels of DMGV were positively associated with body fat percentage, abdominal visceral fat, very low-density lipoprotein cholesterol, and triglycerides, and inversely associated with insulin sensitivity, low-density lipoprotein cholesterol, high-density lipoprotein size, and high-density lipoprotein cholesterol (range of ß coefficients, 0.17-0.46 [SEs, 0.026-0.050]; all P < .001, after adjusting for age and sex). After adjusting for age, sex, and baseline traits, baseline DMGV levels were positively associated with changes in small high-density lipoprotein particles (ß, 0.14 [95% CI, 0.05-0.23]) and inversely associated with changes in medium and total high-density lipoprotein particles (ß, -0.15 [95% CI, -0.24 to -0.05] and -0.19 [95% CI, -0.28 to -0.10], respectively), apolipoprotein A1 (ß, -0.14 [95% CI, -0.23 to -0.05]), and insulin sensitivity (ß, -0.13; P = 3.0 × 10-3) after exercise training. Conclusions and Relevance: Dimethylguanidino valeric acid is an early marker of cardiometabolic dysfunction that is associated with attenuated improvements in lipid traits and insulin sensitivity after exercise training. Levels of DMGV may identify individuals who require additional therapies beyond guideline-directed exercise to improve their metabolic health.

Probing the Virtual Proteome to Identify Novel Disease Biomarkers.

BACKGROUND: Proteomic approaches allow measurement of thousands of proteins in a single specimen, which can accelerate biomarker discovery. However, applying these technologies to massive biobanks is not currently feasible because of the practical barriers and costs of implementing such assays at scale. To overcome these challenges, we used a "virtual proteomic" approach, linking genetically predicted protein levels to clinical diagnoses in >40 000 individuals. METHODS: We used genome-wide association data from the Framingham Heart Study (n=759) to construct genetic predictors for 1129 plasma protein levels. We validated the genetic predictors for 268 proteins and used them to compute predicted protein levels in 41 288 genotyped individuals in the Electronic Medical Records and Genomics (eMERGE) cohort. We tested associations for each predicted protein with 1128 clinical phenotypes. Lead associations were validated with directly measured protein levels and either low-density lipoprotein cholesterol or subclinical atherosclerosis in the MDCS (Malmö Diet and Cancer Study; n=651). RESULTS: In the virtual proteomic analysis in eMERGE, 55 proteins were associated with 89 distinct diagnoses at a false discovery rate q<0.1. Among these, 13 associations involved lipid (n=7) or atherosclerosis (n=6) phenotypes. We tested each association for validation in MDCS using directly measured protein levels. At Bonferroni-adjusted significance thresholds, levels of apolipoprotein E isoforms were associated with hyperlipidemia, and circulating C-type lectin domain family 1 member B and platelet-derived growth factor receptor-ß predicted subclinical atherosclerosis. Odds ratios for carotid atherosclerosis were 1.31 (95% CI, 1.08-1.58; P=0.006) per 1-SD increment in C-type lectin domain family 1 member B and 0.79 (0.66-0.94; P=0.008) per 1-SD increment in platelet-derived growth factor receptor-ß. CONCLUSIONS: We demonstrate a biomarker discovery paradigm to identify candidate biomarkers of cardiovascular and other diseases.

Plasma Metabolite Profiles in Response to Chronic Exercise.

PURPOSE: High-throughput profiling of metabolic status (metabolomics) allows for the assessment of small-molecule metabolites that may participate in exercise-induced biochemical pathways and corresponding cardiometabolic risk modification. We sought to describe the changes in a diverse set of plasma metabolite profiles in patients undergoing chronic exercise training and assess the relationship between metabolites and cardiometabolic response to exercise. METHODS: A secondary analysis was performed in 216 middle-age abdominally obese men and women (mean ± SD, 52.4 ± 8.0 yr) randomized into one of four groups varying in exercise amount and intensity for 6-month duration: high amount high intensity, high amount low intensity, low amount low intensity, and control. One hundred forty-seven metabolites were profiled by liquid chromatography-tandem mass spectrometry. RESULTS: No significant differences in metabolite changes between specific exercise groups were observed; therefore, subsequent analyses were collapsed across exercise groups. There were no significant differences in metabolite changes between the exercise and control groups after 24 wk at a Bonferroni-adjusted statistical significance (P < 3.0 × 10). Seven metabolites changed in the exercise group compared with the control group at P < 0.05. Changes in several metabolites from distinct metabolic pathways were associated with change in cardiometabolic risk traits, and three baseline metabolite levels predicted changes in cardiometabolic risk traits. CONCLUSIONS: Metabolomic profiling revealed no significant plasma metabolite changes between exercise and control after 24 wk at Bonferroni significance. However, we identified circulating biomarkers that were predictive or reflective of improvements in cardiometabolic traits in the exercise group.