Patient-Level Pooled Analysis of Endovascular Ultrasound Renal Denervation or a Sham Procedure 6 Months After Medication Escalation: The RADIANCE Clinical Trial Program.

BACKGROUND: The randomized, sham-controlled RADIANCE-HTN (A Study of the Recor Medical Paradise System in Clinical Hypertension) SOLO, RADIANCE-HTN TRIO, and RADIANCE II (A Study of the Recor Medical Paradise System in Stage II Hypertension) trials independently met their primary end point of a greater reduction in daytime ambulatory systolic blood pressure (SBP) 2 months after ultrasound renal denervation (uRDN) in patients with hypertension. To characterize the longer-term effectiveness and safety of uRDN versus sham at 6 months, after the blinded addition of antihypertensive treatments (AHTs), we pooled individual patient data across these 3 similarly designed trials. METHODS: Patients with mild to moderate hypertension who were not on AHT or with hypertension resistant to a standardized combination triple AHT were randomized to uRDN (n=293) versus sham (n=213); they were to remain off of added AHT throughout 2 months of follow-up unless specified blood pressure (BP) criteria were exceeded. In each trial, if monthly home BP was ≥135/85 mm Hg from 2 to 5 months, standardized AHT was sequentially added to target home BP <135/85 mm Hg under blinding to initial treatment assignment. Six-month outcomes included baseline- and AHT-adjusted change in daytime ambulatory, home, and office SBP; change in AHT; and safety. Linear mixed regression models using all BP measurements and change in AHT from baseline through 6 months were used. RESULTS: Patients (70% men) were 54.1±9.3 years of age with a baseline daytime ambulatory/home/office SBP of 150.5±9.8/151.0±12.4/155.5±14.4 mm Hg, respectively. From 2 to 6 months, BP decreased in both groups with AHT titration, but fewer uRDN patients were prescribed AHT (P=0.004), and fewer additional AHT were prescribed to uRDN patients versus sham patients (P=0.001). Whereas the unadjusted between-group difference in daytime ambulatory SBP was similar at 6 months, the baseline and medication-adjusted between-group difference at 6 months was -3.0 mm Hg (95% CI, -5.7, -0.2; P=0.033), in favor of uRDN+AHT. For home and office SBP, the adjusted between-group differences in favor of uRDN+AHT over 6 months were -5.4 mm Hg (-6.8, -4.0; P<0.001) and -5.2 mm Hg (-7.1, -3.3; P<0.001), respectively. There was no heterogeneity between trials. Safety outcomes were few and did not differ between groups. CONCLUSIONS: This individual patient-data analysis of 506 patients included in the RADIANCE trials demonstrates the maintenance of BP-lowering efficacy of uRDN versus sham at 6 months, with fewer added AHTs. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT02649426 and NCT03614260.

Diverse biological functions of the renin-angiotensin system.

The renin-angiotensin system (RAS) has been widely known as a circulating endocrine system involved in the control of blood pressure. However, components of RAS have been found to be localized in rather unexpected sites in the body including the kidneys, brain, bone marrow, immune cells, and reproductive system. These discoveries have led to steady, growing evidence of the existence of independent tissue RAS specific to several parts of the body. It is important to understand how RAS regulates these systems for a variety of reasons: It gives a better overall picture of human physiology, helps to understand and mitigate the unintended consequences of RAS-inhibiting or activating drugs, and sets the stage for potential new therapies for a variety of ailments. This review fulfills the need for an updated overview of knowledge about local tissue RAS in several bodily systems, including their components, functions, and medical implications.

Efficacy and Safety of Aficamten in Symptomatic Nonobstructive Hypertrophic Cardiomyopathy: Results From the REDWOOD-HCM Trial, Cohort 4.

BACKGROUND: This open-label phase 2 trial evaluated the safety and efficacy of aficamten in patients with nonobstructive hypertrophic cardiomyopathy (nHCM). METHODS: Patients with symptomatic nHCM (left ventricular outflow tract obstruction gradient ≤ 30 mmHg, left ventricular ejection fraction [LVEF] ≥ 60%, N-terminal pro-B-type natriuretic peptide [NT-proBNP] > 300 pg/mL) received aficamten 5-15 mg once daily (doses adjusted according to echocardiographic LVEF) for 10 weeks. RESULTS: We enrolled 41 patients (mean ± SD age 56 ± 16 years; 59% female). At Week 10, 22 (55%) patients experienced an improvement of ≥ 1 New York Heart Association class; 11 (29%) became asymptomatic. Clinically relevant improvements in Kansas City Cardiomyopathy Questionnaire Clinical Summary Scores occurred in 22 (55%) patients. Symptom relief was paralleled by reductions in NT-proBNP levels (56%; P < 0.001) and high-sensitivity cardiac troponin I (22%; P < 0.005). Modest reductions in LVEF (mean ± SD) of -5.4% ± 10 to 64.6% ± 9.1 were observed. Three (8%) patients had asymptomatic reduction in LVEF < 50% (range: 41%-48%), all returning to normal after 2 weeks of washout. One patient with prior history of aborted sudden cardiac death experienced a fatal arrhythmia during the study. CONCLUSIONS: Aficamten administration for symptomatic nHCM was generally safe and was associated with improvements in heart failure symptoms and cardiac biomarkers. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04219826.

Effects of pericardiocentesis on renal function and cardiac hemodynamics.

BACKGROUND: Previous case studies have reported reversal of acute renal failure after pericardiocentesis in pericardial effusion. This study examines the effects of pericardiocentesis on preprocedural low cardiac output and acute renal dysfunction in patients with pericardial effusion. METHODS: This is a retrospective study of 95 patients undergoing pericardiocentesis between 2015 and 2020. Pre- and post-procedure transthoracic echocardiograms (TTE) were reviewed for evidence of cardiac tamponade, resolution of pericardial effusion, and for estimation of right atrial (RA) pressure and cardiac output. Laboratory values were compared at presentation and post-procedure. Patients on active renal replacement therapy were excluded. RESULTS: Ninety-five patients were included for analysis (mean age 62.2 ± 17.8 years, 58% male). There was a significant increase in glomerular filtration rate pre- and post-procedure. Fifty-six patients (58.9%) had an improvement in glomerular filtration rate after pericardiocentesis (termed "responders"), and these patients had a lower pre-procedure glomerular filtration rate than "non-responders." There was a significant improvement in estimated cardiac output and right atrial pressure for patients in both groups. Patients who had an improvement in renal function had significantly lower pre-procedural diastolic blood pressure and mean arterial pressure. CONCLUSIONS: Pericardial drainage may improve effusion-mediated acute renal dysfunction by reducing right atrial pressure and thus systemic venous congestion, and by increasing forward stroke volume and perfusion pressure.

Comparison of prognostic value among echocardiographic surrogates of right ventricular-pulmonary arterial coupling: A three-dimensional echocardiographic study.

OBJECTIVES: Right ventricular (RV)-pulmonary arterial (PA) coupling is important in various cardiac diseases. Recently, several echocardiographic surrogates for RV-PA coupling have been proposed and reported to be useful in predicting outcomes. However, it remains unclear which surrogate is the most clinically relevant. This study aimed to comprehensively compare the prognostic value of different echocardiographic RV-PA coupling surrogates. METHODS: We retrospectively reviewed 242 patients with various cardiac conditions who underwent comprehensive transthoracic echocardiography with three-dimensional RV data. In addition to conventional parameters including tricuspid annular plane systolic excursion (TAPSE), fractional area change (FAC), and PA systolic pressure (PASP), we analyzed RV free wall and global longitudinal strain (FWLS and GLS). We also obtained RV ejection fraction (RVEF), stroke volume (SV), and end-systolic volume (ESV) using three-dimensional RV analysis. RV-PA coupling surrogates were calculated as TAPSE/PASP, FAC/PASP, FWLS/PASP, GLS/PASP, RVEF/PASP, and SV/ESV. The study endpoint was a composite outcome of all-cause death or cardiovascular hospitalization within 1 year. RESULTS: In multivariable analysis, all the RV-PA coupling surrogates were independent predictors of the outcome. Among the surrogates, the model with TAPSE/PASP showed the lowest prognostic value in model fit and discrimination ability, whereas the model with RVEF/PASP exhibited the highest prognostic value. The partial likelihood ratio test indicated that the model with RVEF/PASP was significantly better than the model with TAPSE/PASP (p < .024). CONCLUSION: All the RV-PA coupling surrogates were independent predictors of the outcome. Notably, RVEF/PASP had the highest prognostic value among the surrogates.

Endovascular Ultrasound Renal Denervation to Treat Hypertension: The RADIANCE II Randomized Clinical Trial.

Importance: Two initial sham-controlled trials demonstrated that ultrasound renal denervation decreases blood pressure (BP) in patients with mild to moderate hypertension and hypertension that is resistant to treatment. Objective: To study the efficacy and safety of ultrasound renal denervation without the confounding influence of antihypertensive medications in patients with hypertension. Design, Setting, and Participants: Sham-controlled, randomized clinical trial with patients and outcome assessors blinded to treatment assignment that was conducted between January 14, 2019, and March 25, 2022, at 37 centers in the US and 24 centers in Europe, with randomization stratified by center. Patients aged 18 years to 75 years with hypertension (seated office systolic BP [SBP] ≥140 mm Hg and diastolic BP [DBP] ≥90 mm Hg despite taking up to 2 antihypertensive medications) were eligible if they had an ambulatory SBP/DBP of 135/85 mm Hg or greater and an SBP/DBP less than 170/105 mm Hg after a 4-week washout of their medications. Patients with an estimated glomerular filtration rate of 40 mL/min/1.73 m2 or greater and with suitable renal artery anatomy were randomized 2:1 to undergo ultrasound renal denervation or a sham procedure. Patients were to abstain from antihypertensive medications until the 2-month follow-up unless prespecified BP criteria were exceeded and were associated with clinical symptoms. Interventions: Ultrasound renal denervation vs a sham procedure. Main Outcomes and Measures: The primary efficacy outcome was the mean change in daytime ambulatory SBP at 2 months. The primary safety composite outcome of major adverse events included death, kidney failure, and major embolic, vascular, cardiovascular, cerebrovascular, and hypertensive events at 30 days and renal artery stenosis greater than 70% detected at 6 months. The secondary outcomes included mean change in 24-hour ambulatory SBP, home SBP, office SBP, and all DBP parameters at 2 months. Results: Among 1038 eligible patients, 150 were randomized to ultrasound renal denervation and 74 to a sham procedure (mean age, 55 years [SD, 9.3 years]; 28.6% female; and 16.1% self-identified as Black or African American). The reduction in daytime ambulatory SBP was greater with ultrasound renal denervation (mean, -7.9 mm Hg [SD, 11.6 mm Hg]) vs the sham procedure (mean, -1.8 mm Hg [SD, 9.5 mm Hg]) (baseline-adjusted between-group difference, -6.3 mm Hg [95% CI, -9.3 to -3.2 mm Hg], P < .001), with a consistent effect of ultrasound renal denervation throughout the 24-hour circadian cycle. Among 7 secondary BP outcomes, 6 were significantly improved with ultrasound renal denervation vs the sham procedure. No major adverse events were reported in either group. Conclusions and Relevance: In patients with hypertension, ultrasound renal denervation reduced daytime ambulatory SBP at 2 months in the absence of antihypertensive medications vs a sham procedure without postprocedural major adverse events. Trial Registration: ClinicalTrials.gov Identifier: NCT03614260.

Cost-Effectiveness of Hypertension Treatment by Pharmacists in Black Barbershops.

BACKGROUND: In LABBPS (Los Angeles Barbershop Blood Pressure Study), pharmacist-led hypertension care in Los Angeles County Black-owned barbershops significantly improved blood pressure control in non-Hispanic Black men with uncontrolled hypertension at baseline. In this analysis, 10-year health outcomes and health care costs of 1 year of the LABBPS intervention versus control are projected. METHODS: A discrete event simulation of hypertension care processes projected blood pressure, medication-related adverse events, fatal and nonfatal cardiovascular disease events, and noncardiovascular disease death in LABBPS participants. Program costs, total direct health care costs (2019 US dollars), and quality-adjusted life-years (QALYs) were estimated for the LABBPS intervention and control arms from a health care sector perspective over a 10-year horizon. Future costs and QALYs were discounted 3% annually. High and intermediate cost-effectiveness thresholds were defined as <$50 000 and <$150 000 per QALY gained, respectively. RESULTS: At 10 years, the intervention was projected to cost an average of $2356 (95% uncertainty interval, -$264 to $4611) more per participant than the control arm and gain 0.06 (95% uncertainty interval, 0.01-0.10) QALYs. The LABBPS intervention was highly cost-effective, with a mean cost of $42 717 per QALY gained (58% probability of being highly and 96% of being at least intermediately cost-effective). Exclusive use of generic drugs improved the cost-effectiveness to $17 162 per QALY gained. The LABBPS intervention would be only intermediately cost-effective if pharmacists were less likely to intensify antihypertensive medications when systolic blood pressure was ≥150 mm Hg or if pharmacist weekly time driving to barbershops increased. CONCLUSIONS: Hypertension care delivered by clinical pharmacists in Black barbershops is a highly cost-effective way to improve blood pressure control in Black men.

Utility of transesophageal echocardiogram surveillance after watchman device placement.

BACKGROUND: In atrial fibrillation patients undergoing left atrial appendage occlusion with a Watchman device, surveillance imaging with a transesophageal echocardiogram (TEE) is typically performed at 45 days and 1 year to evaluate for device-related thrombus (DRT) and peri-device leak (PDL) before the cessation of oral anticoagulation. The incidence of these complications is relatively low, and the ideal timing and duration of surveillance is unknown. We sought to evaluate the incidence of DRT and PDL after Watchman placement at 45 days and 1 year to determine the necessity of surveillance TEEs. METHODS: We retrospectively analyzed 361 patients who received a Watchman device between January 2016 and January 2020. Baseline clinical and echocardiographic data, post-procedure antithrombotic therapy, and surveillance echocardiographic data were collected from the NCDR LAAO Registry. Nested backward variable elimination regression was performed to derive independent predictors of the composite outcome of DRT and PDL. RESULTS: A total of 286 patients who had post-procedure TEEs were included in the analysis. At 45 days, 9 patients had DRT (3.2%) and 44 patients had PDL (15.0%). At 1 year, 5 patients had DRT (5.6%) and 8 patients had PDL (8.9%). All DRT at 45 days was treated with continued anticoagulation while no change in protocol occurred with PDL. All DRT at 1 year occurred in new patients without prior thrombus. A history of prior transient ischemic attack (TIA) and thromboembolism was significantly associated with DRT or PDL at 1 year. CONCLUSIONS: We identified several patients with device-related complications at 45 days and 1 year despite appropriate device sizing and adequate use of antithrombotic therapy. The incidence of DRT increased from 45 days to 1 year and occurred in patients without prior thrombus. These findings highlight the importance of surveillance imaging and suggest the potential need for extended surveillance in select patients.

Clinical and echocardiographic differences in three different etiologies of severe mitral stenosis.

BACKGROUND: In our institute, the causes of mitral stenosis (MS) are generally categorized into three main etiologies-rheumatic MS (RMS), degenerative MS with annular and leaflet calcification, and post-clip MS as a consequence of transcatheter mitral valve repair with clips for treating mitral regurgitation. However, clinical differences among the three etiologies are uncertain. METHODS: We retrospectively assessed 293 consecutive patients (53 with RMS, 118 with degenerative MS, and 122 with post-clip MS) who had a three-dimensional (3D) transesophageal echocardiography (TEE) derived mitral valve orifice area (MVA) of ≤1.5 cm2 , and a mean transmitral pressure gradient of ≥5 mmHg on transthoracic echocardiography. RESULTS: Although there was no difference in 3D-TEE-derived MVA among the three groups, patients with post-clip MS had a significantly lower mean transmitral pressure gradient compared to those with either of the other two types of MS (10.8 ([7.9-15.2] mmHg vs. 9.6 [7.3-12.5] mmHg vs. 6.9 [6.0-9.2] mmHg; p < .001). Patients with RMS had a higher prevalence of dyspnea. The independent determinants of dyspnea were pressure half time in RMS, 3D-TEE-derived MVA and estimated right atrial pressure in degenerative MS, and left ventricle ejection fraction in post-clip MS. CONCLUSIONS: Patients with post-clip MS had the lowest mean transmitral pressure gradient, and patients with RMS had the highest prevalence of dyspnea, despite having a similar 3D-TEE-derived MVA. The determinants of dyspnea were different among the three etiologies of MS.

Impact of Percutaneous Edge-to-Edge Repair in Patients With Atrial Functional Mitral Regurgitation.

BACKGROUND: The aim of this study was to clarify the clinical outcomes of patients with atrial functional mitral regurgitation (FMR) who underwent the MitraClip procedure compared with those with conventional FMR and sinus rhythm (SR).Methods and Results:Of 303 patients with FMR who underwent the MitraClip procedure, 40 with "atrial-FMR" defined as FMR with permanent atrial fibrillation and normal left ventricular (LV) function/size and 115 with "sinus-FMR" defined as FMR with SR and LV dysfunction were reviewed. Transthoracic and 3D transesophageal echocardiography, and the cardiac complication rate (composite of all-cause death, heart failure admission, mitral valve (MV) surgery, and redo MitraClip procedure) during the 12-month follow-up were compared between the groups. After the MitraClip procedure, reductions in the mitral annular area and its anteroposterior dimension and in the leaflet closure area were observed in both groups. MV orifice area was smaller with greater transmitral pressure gradient (P<0.05) after the procedure in atrial-FMR patients than in those with sinus-FMR. The prevalence of residual MR was similar, but significant tricuspid regurgitation (TR) was more prevalent in the atrial-FMR group at follow-up. Cardiac complication rate was comparable between groups (20% vs. 25%, P=0.63). CONCLUSIONS: Reduction of MR occurred in atrial-FMR probably because of the increase in leaflet coaptation area. Significant TR was more common after the MitraClip procedure in patients with atrial-FMR than with sinus-FMR. However, mid-term outcomes were comparable between patients with atrial-FMR and sinus-FMR.

Left ventricular outflow tract area after percutaneous transseptal transcatheter mitral valve implantation: A three-dimensional transesophageal echocardiography study.

BACKGROUND: Left ventricular (LV) outflow tract (LVOT) obstruction increases mortality in patients undergoing transcatheter mitral valve implantation (TMVI) in degenerated bioprostheses, annuloplasty rings, and native mitral valves. We aimed to evaluate the LVOT area after TMVI using 3-dimensional (3D) transesophageal echocardiography (TEE) and to investigate the preprocedural cardiac geometry that affects the LVOT area after TMVI. METHODS: We retrospectively reviewed echocardiography data in 43 patients who had TMVI. A change in pressure gradient across LVOT from before to after TMVI (∆PG) and postprocedure 3D LVOT cross-sectional area at the level of the most distal portion of the mitral valve stent that was closest to the LV apex were assessed as evidence of LVOT narrowing. RESULTS: Transcatheter mitral valve implantation with the use of balloon-expandable valve system was performed for 24 bioprostheses, 7 annuloplasty rings, and 12 native valves. Compared to patients without increase in LVOT gradient (∆PG <10 mm Hg; n = 33), patients with increase in LVOT gradient (∆PG ≥10 mm Hg; n = 10) had smaller LV end-systolic volume (LVESV), greater LV ejection fraction (LVEF), and smaller aorto-mitral (AM) angle. The LVOT area at the valve stent distal edge showed strong association with ∆PG (r = -.68, P < .0001). Only a small AM angle was associated with a small LVOT area at the valve stent distal edge on multivariable analysis, independent of LVESV and LVEF. CONCLUSION: Small LV size, preserved LVEF, and small AM angle were associated with LVOT narrowing. 3D-derived AM angle might be independently associated with LVOT narrowing in patients undergoing transcatheter mitral valve-in-valve, valve-in-ring, and valve-in-native valve implantation, independent of LVESV and LVEF.

Sustainability of Blood Pressure Reduction in Black Barbershops.

BACKGROUND: We developed a new model of hypertension care for non-Hispanic black men that links health promotion by barbers to medication management by American Society of Hypertension-certified pharmacists and demonstrated efficacy in a 6-month cluster-randomized trial. The marked reduction in systolic blood pressure (BP) seen at 6 months warranted continuing the trial through 12 months to test sustainability, a necessary precondition for implementation research. METHODS: We enrolled a cohort of 319 black male patrons with systolic BP ≥140 mm Hg at baseline. Fifty-two Los Angeles County barbershops were assigned to either a pharmacist-led intervention or an active control group. In the intervention group, barbers promoted follow-up with pharmacists who prescribed BP medication under a collaborative practice agreement with patrons' primary care providers. In the control group, barbers promoted follow-up with primary care providers and lifestyle modification. After BP assessment at 6 months, the intervention continued with fewer in-person pharmacist visits to test whether the intervention effect could be sustained safely for 1 year while reducing pharmacist travel time. Final BP and safety outcomes were assessed in both groups at 12 months. RESULTS: At baseline, mean systolic BP was 152.4 mm Hg in the intervention group and 154.6 mm Hg in the control group. At 12 months, mean systolic BP fell by 28.6 mm Hg (to 123.8 mm Hg) in the intervention group and by 7.2 mm Hg (to 147.4 mm Hg) in the control group. The mean reduction was 20.8 mm Hg greater in the intervention (95% CI, 13.9-27.7; P<0.0001). A BP <130/80 mm Hg was achieved by 68.0% of the intervention group versus 11.0% of the control group ( P<0.02). These new 12-month efficacy data are statistically indistinguishable from our previously reported 6-month data. No treatment-related serious adverse events occurred in either group over 12 months. Cohort retention at 12 months was 90% in both groups. CONCLUSIONS: Among black male barbershop patrons with uncontrolled hypertension, health promotion by barbers resulted in large and sustained BP reduction over 12 months when coupled with medication management by American Society of Hypertension-certified pharmacists. Broad-scale implementation research is both justified and warranted. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT 02321618.

High Carbon Monoxide Levels from Charcoal Combustion Mask Acute Endothelial Dysfunction Induced by Hookah (Waterpipe) Smoking in Young Adults.

BACKGROUND: Hookah smoking is marketed to youth as a harmless alternative to cigarettes. Although cigarette smoking acutely impairs endothelial function, the effect of smoking fruit-flavored hookah tobacco is unknown. Because charcoal traditionally is used to heat the hookah tobacco in the waterpipe, hookah smoke delivers tobacco toxicants and nicotine plus charcoal combustion products: not only carbon-rich nanoparticles, oxidants that may destroy nitric oxide and impair endothelial function, but also large amounts of carbon monoxide (CO), a putative vasodilator molecule. METHODS: To test the acute effect of hookah smoking on endothelial function, in young adult hookah smokers (n=30, age 26±1 years, mean±SE), we measured plasma nicotine, exhaled CO, and brachial artery flow-mediated dilation (FMD) before and after charcoal-heated hookah smoking. To remove the effect of charcoal combustion, the same measurements were performed when the same flavored hookah tobacco product was heated electrically (n=20). As a positive internal control, we studied age-matched cigarette smokers (n=15) who smoked 1 cigarette. To isolate the effect of the CO boost on FMD, hookah smokers (n=8) inhaled a 0.1% CO gas mixture to approximate their CO boost achieved with charcoal-heated hookah smoking. RESULTS: Nicotine levels increased similarly with all types of smoking, whereas exhaled CO increased 9- to 10-fold more after charcoal-heated hookah than after either electrically heated hookah or cigarette smoking. FMD did not decrease after smoking charcoal-heated hookah but instead increased by +43±7% ( P<0.001). In contrast, FMD decreased by -27±4% ( P<0.001) after smoking electrically heated hookah, comparable to the decrease after cigarette smoking. FMD increased markedly by 138±71% ( P<0.001) after breathing CO gas, 2.8 times more than the increase induced in the same subjects after smoking charcoal-heated hookah ( P<0.001), despite comparable increases in exhaled CO (24±1 versus 28±3 ppm, hookah versus CO). CONCLUSIONS: Smoking hookah tobacco, similar to cigarette tobacco, acutely impairs endothelial function. With traditional charcoal-heated hookah smoking, the acute endothelial dysfunction is masked by high levels of carbon monoxide, a potent vasodilator molecule generated by charcoal combustion. With respect to large-artery endothelial function, smoking hookah is not harmless. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifiers: NCT03616002 and NCT03067701.

Six-Month Results of Treatment-Blinded Medication Titration for Hypertension Control After Randomization to Endovascular Ultrasound Renal Denervation or a Sham Procedure in the RADIANCE-HTN SOLO Trial.

BACKGROUND: The multicenter, international, randomized, blinded, sham-controlled RADIANCE-HTN SOLO trial (A Study of the ReCor Medical Paradise System in Clinical Hypertension) demonstrated a 6.3 mm Hg greater reduction in daytime ambulatory systolic blood pressure (BP) at 2 months by endovascular ultrasound renal denervation (RDN) compared with a sham procedure among patients not treated with antihypertensive medications. We report 6-month results after the addition of a recommended standardized stepped-care antihypertensive treatment to the randomized endovascular procedure under continued blinding to initial treatment. METHODS: Patients with a daytime ambulatory BP ≥135/85 mm Hg and <170/105 mm Hg after a 4-week discontinuation of up to 2 antihypertensive medications, and a suitable renal artery anatomy, were randomized to RDN (n=74) or sham (n=72). Patients were to remain off antihypertensive medications throughout the first 2 months of follow-up unless safety BP criteria were exceeded. Between 2 and 5 months, if monthly measured home BP was ≥135/85 mm Hg, a standardized stepped-care antihypertensive treatment was recommended consisting of the sequential addition of amlodipine (5 mg/d), a standard dose of an angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, and hydrochlorothiazide (12.5 mg/d), followed by the sequential uptitration of hydrochlorothiazide (25 mg/d) and amlodipine (10 mg/d). Outcomes included the 6-month (1) change in daytime ambulatory systolic BP adjusted for medications and baseline systolic BP, (2) medication burden, and (3) safety. RESULTS: A total of 69/74 RDN patients and 71/72 sham patients completed the 6-month ambulatory BP measurement. At 6 months, 65.2% of patients in the RDN group were treated with the standardized stepped-care antihypertensive treatment versus 84.5% in the sham group (P=0.008), and the average number of antihypertensive medications and defined daily dose were less in the RDN group than in the sham group (0.9±0.9 versus 1.3±0.9, P=0.010 and 1.4±1.5 versus 2.0±1.8, P=0.018; respectively). Despite less intensive standardized stepped-care antihypertensive treatment, RDN reduced daytime ambulatory systolic BP to a greater extent than sham (-18.1±12.2 versus -15.6±13.2 mm Hg, respectively; difference adjusted for baseline BP and number of medications: -4.3 mm Hg, 95% confidence interval, -7.9 to -0.6, P=0.024). There were no major adverse events in either group through 6 months. CONCLUSIONS: The BP-lowering effect of endovascular ultrasound RDN was maintained at 6 months with less prescribed antihypertensive medications compared with a sham control. CLINICAL TRIAL REGISTRATION: URL: https://www. CLINICALTRIALS: gov. Unique identifier: NCT02649426.

Barbershop Management of Hypertension in the African American Population: Pitfalls and Opportunities for Extension to Other Underserved Communities.

PURPOSE OF REVIEW: This review summarizes the results of recent barbershop-based studies focusing on the diagnosis and management of hypertension (HTN) in black adults. The pitfalls of prior attempts and opportunities for the development of future programs to address health disparities on a larger scale are also reviewed. RECENT FINDINGS: While barbershop health outreach has become a commonplace in recent years, the quality of the evidence on the effectiveness of such programs has been weak, until the Los Angeles Barbershop Blood Pressure Study (LABBPS), a rigorously carried out cluster-randomized trial, demonstrated a - 21 mmHg greater reduction in BP among black hypertensive men who were assigned to a pharmacist-led HTN intervention when compared with usual care. Given the available evidence, barber health promotion paired with focused hypertension-specialty care has the potential to reduce, if not eliminate, the present wide gap in hypertension care and ultimately lead to a reduction of hypertension-related complications among blacks. Future research should seek to improve the scalability and transferability of the LABBPS model both to other geographic regions and to other at-risk groups.

Impact of Obesity in Hospitalized Patients with Heart Failure: A Nationwide Cohort Study.

OBJECTIVES: Obesity and cardiovascular disease remain significant burdens on the overall provision of health care in the United States. Obesity has been shown to be a direct risk factor for heart failure (HF). We conducted a nationwide cohort study to assess the short-term impact of obesity in hospitalized patients with HF. METHODS: We identified 1,520,871 encounters with a primary diagnosis of HF in the 2013-2014 Nationwide Readmission Database. We excluded patients younger than 18 years (n = 2755), hospitalized patients discharged in December (n = 126,137), patients with missing mortality information (n = 477), missing length of stay (LOS; n = 91), patients who were transferred to another hospital (n = 38,489), and patients with conflicting body weight information (n = 7757). Multivariable logistic regression was used to evaluate the association between baseline characteristics (including the presence of obesity) and in-hospital mortality, as well as 30-day readmission rates. RESULTS: The overall in-patient mortality rate was 2.8% (n = 37,927). Obese patients had numerically a lower mortality (1.8%) compared with the nonobese patients (3.1%); however, the difference in risk was not significant on multivariable analysis (hazard ratio 0.97, 95% confidence interval 0.94-1.01). In the overall cohort, 20.6% (n = 269,988) were readmitted within 30 days. The risk of 30-day readmission was significantly lower in obese patients (19.4%) compared with nonobese patients (20.9%) (odds ratio 0.85, 95% confidence interval 0.84-0.86). Obese patients had longer LOSs (median of 5 days [3-7] vs 4 days [2-6], P < 0.001) and higher costs of index admission (median of $27,206 [$16,027-$48,316] vs $23,339 [$13,698-$41,982], P < 0.001) compared with nonobese patients. CONCLUSIONS: In this cross-sectional study of patients hospitalized for HF in the United States, obesity was not associated with a higher risk of inpatient mortality, but it was associated with a lower 30-day readmission rate. Obese patients with HF, however, had longer LOSs and higher costs of index admission. Our findings support the obesity paradox seen in patients with HF.

Endovascular ultrasound renal denervation to treat hypertension (RADIANCE-HTN SOLO): a multicentre, international, single-blind, randomised, sham-controlled trial.

BACKGROUND: Early studies suggest that radiofrequency-based renal denervation reduces blood pressure in patients with moderate hypertension. We investigated whether an alternative technology using endovascular ultrasound renal denervation reduces ambulatory blood pressure in patients with hypertension in the absence of antihypertensive medications. METHODS: RADIANCE-HTN SOLO was a multicentre, international, single-blind, randomised, sham-controlled trial done at 21 centres in the USA and 18 in Europe. Patients with combined systolic-diastolic hypertension aged 18-75 years were eligible if they had ambulatory blood pressure greater than or equal to 135/85 mm Hg and less than 170/105 mm Hg after a 4-week discontinuation of up to two antihypertensive medications and had suitable renal artery anatomy. Patients were randomised (1:1) to undergo renal denervation with the Paradise system (ReCor Medical, Palo Alto, CA, USA) or a sham procedure consisting of renal angiography only. The randomisation sequence was computer generated and stratified by centres with randomised blocks of four or six and permutation of treatments within each block. Patients and outcome assessors were blinded to randomisation. The primary effectiveness endpoint was the change in daytime ambulatory systolic blood pressure at 2 months in the intention-to-treat population. Patients were to remain off antihypertensive medications throughout the 2 months of follow-up unless specified blood pressure criteria were exceeded. Major adverse events included all-cause mortality, renal failure, an embolic event with end-organ damage, renal artery or other major vascular complications requiring intervention, or admission to hospital for hypertensive crisis within 30 days and new renal artery stenosis within 6 months. This study is registered with ClinicalTrials.gov, number NCT02649426. FINDINGS: Between March 28, 2016, and Dec 28, 2017, 803 patients were screened for eligibility and 146 were randomised to undergo renal denervation (n=74) or a sham procedure (n=72). The reduction in daytime ambulatory systolic blood pressure was greater with renal denervation (-8·5 mm Hg, SD 9·3) than with the sham procedure (-2·2 mm Hg, SD 10·0; baseline-adjusted difference between groups: -6·3 mm Hg, 95% CI -9·4 to -3·1, p=0·0001). No major adverse events were reported in either group. INTERPRETATION: Compared with a sham procedure, endovascular ultrasound renal denervation reduced ambulatory blood pressure at 2 months in patients with combined systolic-diastolic hypertension in the absence of medications. FUNDING: ReCor Medical.

Sustainability of blood pressure reduction in black barbershops.

PURPOSE OF REVIEW: The prevalence of hypertension (HTN) among non-Hispanic blacks increased from 41 to 55% with the release of the new 2017 ACC/AHA guidelines - the highest among any racial group. Non-Hispanic black men have less physician interaction and lower blood pressure (BP) treatment and control rates when compared with their female counterparts, necessitating community outreach. Here, we review the Los Angeles Barbershop Blood Pressure Study (LABBPS) which demonstrated a community-based approach involving pharmacists, physicians, and barbers could improve BP control rates among black men. RECENT FINDINGS: LABBPS was a cluster-randomized trial that evaluated both the efficacy and sustainability of a pharmacist-led HTN management program in which barbers promoted follow-up with pharmacists who prescribed antihypertensive therapy under collaborative practice agreements with intervention participant's primary care providers. After 6 months researchers observed a 21 mmHg greater fall in SBP among intervention group participants when compared with the control group participants who received 'usual care.' The 6-month extension phase of the study showed that the impressive BP reduction achieved was sustained with less pharmacist contact. SUMMARY: Multidisciplinary, community-based approaches to HTN management can be effective and are necessary to tackle the current disparity seen in BP control rates. The model developed in LABBPS represents one such approach.

Degenerative Mitral Regurgitation: Assessment, Physical Examination, and Imaging.

PURPOSE OF REVIEW: In this review, we provide a comprehensive approach to assess degenerative mitral regurgitation. RECENT FINDINGS: In the evaluation of MR, it is important to differentiate between primary (degenerative/organic) MR in which an intrinsic mitral valve lesion(s) is responsible for the occurrence of MR and secondary (functional) MR where the mitral valve is structurally normal, but alterations of the left ventricular geometry cause deterioration of the MV apparatus. Advanced imaging modalities, foremost two-dimensional and three-dimensional echocardiography, are essential for this determination. In the evaluation of degenerative MR, the exact mechanism, the extent of the disease, associated valve lesions, the grade of mitral regurgitation severity, and hemodynamic consequences require careful assessment in order to provide patients with appropriate monitoring and treatment.