Systolic Blood Pressure in Heart Failure With Preserved Ejection Fraction Treated With Sacubitril/Valsartan

BackgroundGuidelines recommend targeting systolic blood pressure (SBP) <130 mm Hg in heart failure with preserved ejection fraction (HFpEF) with limited data.ObjectivesThis study sought to determine the optimal achieved SBP and whether the treatment effects of sacubitril/valsartan on outcomes are related to BP lowering, particularly among women who derive greater benefit from sacubitril/valsartan.MethodsUsing 4,795 trial participants, this study related baseline and time-updated mean achieved SBP quartiles (<120, 120 to 129, 130 to 139, ≥140 mm Hg) to the primary outcome (cardiovascular death and total heart failure hospitalization), its components, myocardial infarction or stroke, and a renal composite outcome. At the 16-week visit, the study assessed the relationship between SBP change and Kansas City Cardiomyopathy Questionnaire overall summary score (KCCQ-OSS) and N-terminal pro−B-type natriuretic peptide (NT-proBNP). The study analyzed whether the BP-lowering effects of sacubitril/valsartan accounted for its treatment effects.ResultsAverage age was 73 ± 8 years, and 52% of participants were women. After multivariable adjustment, baseline and mean achieved SBP of 120 to 129 mm Hg demonstrated the lowest risk for all outcomes. Sacubitril/valsartan reduced SBP by 5.2 mm Hg (95% confidence interval: 4.4 to 6.0) compared with valsartan at 4 weeks, which was not modified by baseline SBP. However, sacubitril/valsartan reduced SBP more in women (6.3 mm Hg) than men (4.0 mm Hg) (interaction p = 0.005). Change in SBP was directly associated with change in NT-proBNP (p < 0.001) but not KCCQ-OSS (p = 0.40). The association between sacubitril/valsartan and the primary outcome was not modified by baseline SBP (interaction p = 0.50) and was similar when adjusting for time-updated SBP, regardless of sex.ConclusionsBaseline and mean achieved SBP of 120 to 129 mm Hg identified the lowest risk patients with HFpEF. Baseline SBP did not modify the treatment effect of sacubitril/valsartan, and the BP-lowering effects of sacubitril/valsartan did not account for its effects on outcomes, regardless of sex. (Prospective Comparison of ARNI With ARB Global Outcomes in HF With Preserved Ejection Fraction [PARAGON-HF]; NCT01920711)     

The REDUCE HTN: REINFORCE: Randomized,Sham-Controlled Trial of Bipolar Radiofrequency Renal Denervation for the Treatment of Hypertension

ObjectivesThe aim of this study was to investigate bipolar radiofrequency renal denervation in patients with hypertension not receiving medications at baseline.BackgroundA blood pressure–reducing effect of renal denervation has been difficult to isolate in clinical investigations.MethodsREDUCE HTN: REINFORCE (Renal Denervation Using the Vessix Renal Denervation System for the Treatment of Hypertension) was a randomized, sham-controlled multicenter trial. Patients with office systolic blood pressure (SBP) of 150 to 180 mm Hg and average 24-h ambulatory SBP of 135 to 170 mm Hg after medication washout underwent bipolar radiofrequency renal denervation or a sham procedure. The planned outcome was 8-week change in 24-h ambulatory SBP. Enrollment was terminated for apparent futility before a sufficient sample for powered efficacy comparisons was enrolled. Safety assessments included all-cause death, renal failure, severe hypotension or syncope, hypertensive crisis, and renal artery stenosis.ResultsBaseline 24-h blood pressure was 148.3 ± 10.9/85.7 ± 9.1 mm Hg for the denervation group (n = 34, mean age 58.5 ± 10.1 years, 47% women) and 149.1 ± 7.2/86.4 ± 9.8 mm Hg for the control group (n = 17, mean age 58.2 ± 9.8 years, 24% women). At 8 weeks, mean 24-h SBP reductions for the renal denervation and control groups were −5.3 mm Hg (95% confidence interval [CI]: −8.8 to −1.8 mm Hg) and −8.5 mm Hg (95% CI: −13.3 to −3.8 mm Hg), respectively (difference 3.3 mm Hg; 95% CI: −2.8 to 9.3 mm Hg; p = 0.30). Antihypertensive medications could then be added. By 6 months, decreases in SBP were greater for the denervation group, yielding between-group differences of −7.2 mm Hg (95% CI: −15.2 to 0.8 mm Hg; p = 0.08), −9.7 mm Hg (95% CI: −17.7 to −1.7 mm Hg; p = 0.02), and −11.4 mm Hg (95% CI: −19.2 to −3.7 mm Hg; p < 0.01) for 24-h, daytime ambulatory, and office measurements, respectively. Through 12 months, 1 patient (renal denervation group) had a hypertensive urgency requiring immediate management, and 1 experienced progression of renal artery stenosis.ConclusionsFuture studies of radiofrequency renal denervation must anticipate delayed treatment effects. (Renal Denervation Using the Vessix Renal Denervation System for the Treatment of Hypertension [REDUCE HTN: REINFORCE]; NCT02392351)     

Impact of Pre-Procedural Blood Pressure on Long-Term Outcomes Following Percutaneous Coronary Intervention

BackgroundHigh systolic blood pressure (SBP) increases cardiac afterload, whereas low diastolic blood pressure (DBP) may lead to impaired coronary perfusion. Thus, wide pulse pressure (high systolic, low diastolic [HSLD]) may contribute to myocardial ischemia and also be a predictor of adverse cardiovascular events.ObjectivesThe purpose of this study was to determine the relationship between pre-procedural blood pressure and long-term outcome following percutaneous coronary intervention (PCI).MethodsThe study included 10,876 consecutive patients between August 2009 and December 2016 from the Melbourne Interventional Group registry undergoing PCI with pre-procedural blood pressure recorded. Patients with ST-segment elevation myocardial infarction, cardiogenic shock, and out-of-hospital cardiac arrest were excluded. Patients were divided into 4 groups according to SBP (high ≥120 mm Hg, low <120 mm Hg) and DBP (high >70 mm Hg, low ≤70 mm Hg).ResultsMean pulse pressure was 60 ± 21 mm Hg. Patients with HSLD were older and more frequently women, with higher rates of hypercholesterolemia, renal impairment, diabetes, and multivessel and left main disease (all p ≤ 0.0001). There was no difference in 30-day major adverse cardiac events, but at 12 months the HSLD group had a greater incidence of myocardial infarction (p = 0.018) and stroke (p = 0.013). Long-term mortality was highest for HSLD (7.9%) and lowest for low systolic, high diastolic (narrow pulse pressure) at 2.1% (p = 0.0002). Cox regression analysis demonstrated significantly lower long-term mortality in the low systolic, high diastolic cohort (hazard ratio: 0.50; 99% confidence interval: 0.25 to 0.98; p = 0.04).ConclusionsPulse pressure at the time of index PCI is associated with long-term outcomes following PCI. A wide pulse pressure may serve as a surrogate marker for risk following PCI and represents a potential target for future therapies.     

Effects of Diet and Sodium Reduction on Cardiac Injury,Strain, and Inflammation: The DASH-Sodium Trial

BackgroundThe DASH (Dietary Approaches to Stop Hypertension) diet has been determined to have beneficial effects on cardiac biomarkers. The effects of sodium reduction on cardiac biomarkers, alone or combined with the DASH diet, are unknown.ObjectivesThe purpose of this study was to determine the effects of sodium reduction and the DASH diet, alone or combined, on biomarkers of cardiac injury, strain, and inflammation.MethodsDASH-Sodium was a controlled feeding study in adults with systolic blood pressure (BP) 120 to 159 mm Hg and diastolic BP 80 to 95 mm Hg, randomly assigned to the DASH diet or a control diet. On their assigned diet, participants consumed each of three sodium levels for 4 weeks. Body weight was kept constant. At the 2,100 kcal level, the 3 sodium levels were low (50 mmol/day), medium (100 mmol/day), and high (150 mmol/day). Outcomes were 3 cardiac biomarkers: high-sensitivity cardiac troponin I (hs-cTnI) (measure of cardiac injury), N-terminal pro–B-type natriuretic peptide (NT-proBNP) (measure of strain), and high-sensitivity C-reactive protein (hs-CRP) (measure of inflammation), collected at baseline and at the end of each feeding period.ResultsOf the original 412 participants, the mean age was 48 years; 56% were women, and 56% were Black. Mean baseline systolic/diastolic BP was 135/86 mm Hg. DASH (vs. control) reduced hs-cTnI by 18% (95% confidence interval [CI]: ?27% to ?7%) and hs-CRP by 13% (95% CI: ?24% to ?1%), but not NT-proBNP. In contrast, lowering sodium from high to low levels reduced NT-proBNP independently of diet (19%; 95% CI: ?24% to ?14%), but did not alter hs-cTnI and mildly increased hs-CRP (9%; 95% CI: 0.4% to 18%). Combining DASH with sodium reduction lowered hs-cTnI by 20% (95% CI: ?31% to ?7%) and NT-proBNP by 23% (95% CI: ?32% to ?12%), whereas hs-CRP was not significantly changed (?7%; 95% CI: ?22% to 9%) compared with the high sodium-control diet.ConclusionsCombining a DASH dietary pattern with sodium reduction can lower 2 distinct mechanisms of subclinical cardiac damage: injury and strain, whereas DASH alone reduced inflammation. (Dietary Patterns, Sodium Intake and Blood Pressure [DASH – Sodium]; NCT00000608)     

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

BackgroundIntensive systolic blood pressure (SBP) treatment prevents cardiovascular disease (CVD) events in patients with high CVD risk on average, though benefits likely vary among patients.ObjectivesThe 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.MethodsThis 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.ResultsAmong 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.ConclusionsSPRINT 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)     

Lower levels of plasma NT-proBNP are associated with higher prevalence of NASH in patients with biopsy-proven NAFLD

Background and aimsEmerging evidence suggests that plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) levels are decreased in patients with imaging-defined nonalcoholic fatty liver disease (NAFLD), but no data are currently available on the association between plasma NT-proBNP levels and the histological severity of NAFLD.Methods and resultsWe enrolled 351 (73.5% men) consecutive adult patients with biopsy-proven NAFLD without a prior history of cardiovascular disease (CVD). Plasma NT-proBNP levels were measured using a commercially available immunochemical system (VITROS® 5600, Johnson, New Jersey). Fifty-three percent of these subjects had nonalcoholic steatohepatitis (NASH). After stratification of patients by plasma NT-proBNP tertiles; compared to those in the 1st tertile (NT-proBNP ≤16 pg/ml), the odds ratio for NASH was 0.52 (95% CI 0.29–0.95) in patients in the 2nd tertile (NT-proBNP of 17–33 pg/ml) and 0.49 (95% CI 0.26–0.93) in those in the 3rd tertile (NT-proBNP ≥34 pg/ml) of plasma NT-proBNP levels, even after adjustment for age, sex, body mass index, homeostasis model assessment (HOMA)-estimated insulin resistance, pre-existing diabetes, hypertension, and dyslipidemia.ConclusionIn subjects with biopsy-proven NAFLD without known CVD, this cross-sectional study shows for the first time, that lower plasma NT-proBNP levels are strongly associated with a higher prevalence of NASH.     

Systolic Blood Pressure and Outcomes in Patients With Heart Failure With Reduced Ejection Fraction

BackgroundNational guidelines recommend that systolic blood pressure (SBP) in patients with heart failure with reduced ejection fraction (HFrEF) and hypertension be maintained below 130 mm Hg.ObjectivesThis study sought to determine associations of SBP <130 mm Hg with outcomes in patients with HFrEF.MethodsOf the 25,345 patients in the Medicare-linked OPTIMIZE-HF registry, 10,535 had an ejection fraction (EF) ≤40%. Of these, 5,615 had stable SBP (≤20 mm Hg admission to discharge variation), and 3,805 (68%) had a discharge SBP <130 mm Hg. Propensity scores for SBP <130 mm Hg, estimated for each of the 5,615 patients, were used to assemble a matched cohort of 1,189 pairs of patients with SBP <130 versus ≥130 mm Hg, balanced on 58 baseline characteristics (mean age 76 years; mean EF 28%, 45% women, 13% African American). This process was repeated in 3,946 patients, after excluding 1,669 patients (30% of 5,615) with a discharge SBP <110 mm Hg and assembled a second matched balanced cohort of 1,099 pairs of patients with SBP 110 to 129 mm Hg versus ≥130 mm Hg.ResultsThirty-day all-cause mortality occurred in 7% and 4% of matched patients with SBP <130 mm Hg versus ≥130 mm Hg, respectively (hazard ratio [HR]: 1.76; 95% confidence interval [CI]: 1.24 to 2.48; p = 0.001). HRs (95% CIs) for all-cause mortality, all-cause readmission, and HF readmission at 1 year, associated with SBP <130 mm Hg, were 1.32 (1.15 to 1.53; p < 0.001), 1.11 (1.01 to 1.23; p = 0.030), and 1.24 (1.09 to 1.42; p = 0.001), respectively. HRs (95% CIs) for 30-day and 1-year all-cause mortality associated with SBP 110 to 129 mm Hg (vs. ≥130 mm Hg) were 1.50 (1.03 to 2.19; p = 0.035), and 1.19 (1.02 to 1.39; p = 0.029), respectively.ConclusionsAmong hospitalized older patients with HFrEF, SBP <130 mm Hg is associated with poor outcomes. This association persisted when the analyses were repeated after excluding patients with SBP <110 mm Hg. There is an urgent need for randomized controlled trials to evaluate optimal SBP reduction goals in patients with HFrEF.     

Group Medical Visit and Microfinance Intervention for Patients With Diabetes or Hypertension in Kenya

BackgroundIncorporating social determinants of health into care delivery for chronic diseases is a priority.ObjectivesThe goal of this study was to evaluate the impact of group medical visits and/or microfinance on blood pressure reduction.MethodsThe authors conducted a cluster randomized trial with 4 arms and 24 clusters: 1) usual care (UC); 2) usual care plus microfinance (MF); 3) group medical visits (GMVs); and 4) GMV integrated into MF (GMV-MF). The primary outcome was 1-year change in systolic blood pressure (SBP). Mixed-effects intention-to-treat models were used to evaluate the outcomes.ResultsA total of 2,890 individuals (69.9% women) were enrolled (708 UC, 709 MF, 740 GMV, and 733 GMV-MF). Average baseline SBP was 157.5 mm Hg. Mean SBP declined ?11.4, ?14.8, ?14.7, and ?16.4 mm Hg in UC, MF, GMV, and GMV-MF, respectively. Adjusted estimates and multiplicity-adjusted 98.3% confidence intervals showed that, relative to UC, SBP reduction was 3.9 mm Hg (?8.5 to 0.7), 3.3 mm Hg (?7.8 to 1.2), and 2.3 mm Hg (?7.0 to 2.4) greater in GMV-MF, GMV, and MF, respectively. GMV and GMV-MF tended to benefit women, and MF and GMV-MF tended to benefit poorer individuals. Active participation in GMV-MF was associated with greater benefit.ConclusionsA strategy combining GMV and MF for individuals with diabetes or hypertension in Kenya led to clinically meaningful SBP reductions associated with cardiovascular benefit. Although the significance threshold was not met in pairwise comparison hypothesis testing, confidence intervals for GMV-MF were consistent with impacts ranging from substantive benefit to neutral effect relative to UC. Incorporating social determinants of health into care delivery for chronic diseases has potential to improve outcomes. (Bridging Income Generation With Group Integrated Care [BIGPIC]; NCT02501746)     

Evaluation of Mavacamten in Symptomatic Patients With Nonobstructive Hypertrophic Cardiomyopathy

BackgroundPatients with nonobstructive hypertrophic cardiomyopathy (nHCM) often experience a high burden of symptoms; however, there are no proven pharmacological therapies. By altering the contractile mechanics of the cardiomyocyte, myosin inhibitors have the potential to modify pathophysiology and improve symptoms associated with HCM.ObjectivesMAVERICK-HCM (Mavacamten in Adults With Symptomatic Non-Obstructive Hypertrophic Cardiomyopathy) explored the safety and efficacy of mavacamten, a first-in-class reversible inhibitor of cardiac-specific myosin, in nHCM.MethodsThe MAVERICK-HCM trial was a multicenter, double-blind, placebo-controlled, dose-ranging phase II study in adults with symptomatic nHCM (New York Heart Association functional class II/III), left ventricular ejection fraction (LVEF) ≥55%, and N-terminal pro−B-type natriuretic peptide (NT-proBNP) ≥300 pg/ml. Participants were randomized 1:1:1 to mavacamten at a pharmacokinetic-adjusted dose (targeting plasma levels of 200 or 500 ng/ml), or placebo for 16 weeks, followed by an 8-week washout. Initial dose was 5 mg daily with 1 dose titration at week 6.ResultsFifty-nine participants were randomized (19, 21, 19 patients to 200 ng/ml, 500 ng/ml, placebo, respectively). Their mean age was 54 years, and 58% were women. Serious adverse events occurred in 10% of participants on mavacamten and in 21% participants on placebo. Five participants on mavacamten had reversible reduction in LVEF ≤45%. NT-proBNP geometric mean decreased by 53% in the pooled mavacamten group versus 1% in the placebo group, with geometric mean differences of −435 and −6 pg/ml, respectively (p = 0.0005). Cardiac troponin I (cTnI) geometric mean decreased by 34% in the pooled mavacamten group versus a 4% increase in the placebo group, with geometric mean differences of −0.008 and 0.001 ng/ml, respectively (p = 0.009).ConclusionsMavacamten, a novel myosin inhibitor, was well tolerated in most subjects with symptomatic nHCM. Furthermore, treatment was associated with a significant reduction in NT-proBNP and cTnI, suggesting improvement in myocardial wall stress. These results set the stage for future studies of mavacamten in this patient population using clinical parameters, including LVEF, to guide dosing. (A Phase 2 Study of Mavacamten in Adults With Symptomatic Non-Obstructive Hypertrophic Cardiomyopathy [MAVERICK-HCM]; NCT03442764)     

Prognosis of Severe Low-Flow,Low-Gradient Aortic Stenosis by Stroke Volume Index and Transvalvular Flow Rate

ObjectivesThis study determined whether flow state classified by stroke volume index (SVi) or transvalvular flow rate (FR) improved risk stratification of all-cause mortality, hospitalization due to heart failure, and aortic valvular interventions for patients with severe aortic stenosis (AS).BackgroundSVi is a widely accepted classification for flow state in severe low-flow, low-gradient (LFLG) AS. Recent studies suggest that FR more closely approximates true AS severity and provides more useful prognostication than SVi.MethodsPatients with severe AS over a 7-year period were subclassified by echocardiographic parameters. LFLG-AS was defined as severe AS (aortic valve area index [AVAi]: <0.6 cm²/m²), with a mean transvalvular pressure gradient of <40 mm Hg in the setting of low flow state: SVi of <35 ml/m² and/or FR of <200 ml/s and subclassified into preserved (≥50%; paradoxical) or reduced (<50%; classical) left ventricular ejection fraction (LVEF).ResultsAmong 621 consecutive patients with severe AS, the proportions of patients classified as LFLG-AS were different between SVi and FR (p < 0.001). Classification using SVi, FR, and LVEF was a strong predictor of the composite endpoint at the 2-year follow-up. The addition of SVi to the echocardiographic and clinical model provided significant improvement in reclassification (net reclassification improvement: 0.089; 95% confidence interval [CI]: 0.045 to 0.133; p = 0.04), whereas addition of FR did not (net reclassification improvement: 0.061; 95% CI: 0.016 to 0.106; p = 0.17). C-statistics indicated improved risk discrimination when AVAi, LVEF, and SVi or FR were added as predictive variables to the clinical model (p = 0.006).ConclusionsLow SVi or FR was associated with adverse cardiovascular events and showed improvement in discrimination, but only SVi, not FR, significantly improved risk reclassification compared to other conventional clinical and echocardiographic predictors. This suggests that FR is not superior to SVi in distinguishing true severe from pseudosevere forms of AS and identification of patients with LFLG-AS who have worse outcomes.     

Alcohol-Mediated Renal Denervation Using the Peregrine System Infusion Catheter for Treatment of Hypertension

ObjectivesThe aim of this multicenter, open-label trial was to evaluate the safety and efficacy of alcohol-mediated renal denervation using a novel catheter system (the Peregrine System Infusion Catheter) for the infusion of dehydrated alcohol as a neurolytic agent into the renal periarterial space.BackgroundThe number of hypertensive patients with uncontrolled blood pressure (BP) remains unacceptably high. The renal sympathetic nervous system has been identified as an attractive therapeutic target.MethodsForty-five patients with uncontrolled hypertension on ≥3 antihypertensive medications underwent bilateral renal denervation using the Peregrine Catheter with 0.6 ml alcohol infused per renal artery.ResultsAll patients were treated as intended. Mean 24-h ambulatory BP reduction at 6 months versus baseline was −11 mm Hg (95% confidence interval [CI]: −15 to −7 mm Hg) for systolic BP and −7 mm Hg (95% CI: −9 to −4 mm Hg) for diastolic BP (p < 0.001 for both). Office systolic BP was reduced by −18/−10 mm Hg (95% CI: −25 to −12/−13 to −6 mm Hg) at 6 months. Antihypertensive medications were reduced in 23% and increased in 5% of patients at 6 months. Adherence to the antihypertensive regimen remained stable over time. The primary safety endpoint, defined as the absence of periprocedural major vascular complications, major bleeding, acute kidney injury, or death within 1 month, was met in 96% of patients (95% CI: 85% to 99%). Two patients had major adverse events of periprocedural access-site pseudoaneurysms, with major bleeding in one. There were no deaths or instances of myocardial infarction, stroke, transient ischemic attack, or renal artery stenosis. Transient microleaks were noted in 42% and 49% of the left and right main renal arteries, respectively. There were 2 cases of minor vessel dissection that resolved without treatment.ConclusionsPrimary results from this trial suggest that alcohol-mediated renal denervation using the Peregrine Catheter safely reduces blood pressure and as such may represent a novel approach for the treatment of hypertension.     

Systolic Blood Pressure Time in Target Range and Cardiovascular Outcomes in Patients With Hypertension

BackgroundStandard blood pressure control metrics may not account for fluctuations in blood pressure over time.ObjectivesThis study sought to estimate the independent association between time in systolic blood pressure target range and major adverse cardiovascular events among adults with hypertension.MethodsThis study was a post hoc analysis of SPRINT (Systolic Blood Pressure Intervention Trial), a randomized clinical trial that compared intensive (<120 mm Hg) and standard (<140 mm Hg) systolic blood pressure treatment interventions in adults with hypertension and high cardiovascular risk. Target range was defined as 110 to 130 mm Hg and 120 to 140 mm Hg for the intensive and standard arms, respectively. Time in target range was estimated over the first 3 months of follow-up using linear interpolation. The association between time in target range with major adverse cardiovascular events was estimated using adjusted Cox proportional hazards regression models.ResultsParticipants with greater time in target range were younger, had lower 10-year cardiovascular risk and lower baseline systolic blood pressure, and were more likely women and statin users. Each 1-SD increase in time in target range was significantly associated with a decreased risk of first major adverse cardiovascular event in fully adjusted models. Time in target range remained significantly associated with major adverse cardiovascular events despite adjustment for mean systolic blood pressure or systolic blood pressure variability. Among participants with mean systolic blood pressure at or below target, time in target range remained associated with major adverse cardiovascular events.ConclusionsTime in systolic blood pressure target range independently predicts major adverse cardiovascular event risk.     

12-Month Results From the Unblinded Phase of the RADIANCE-HTN SOLO Trial of Ultrasound Renal Denervation

ObjectivesThis study reports the 12-month results of the RADIANCE-HTN (A Study of the ReCor Medical Paradise System in Clinical Hypertension) SOLO trial following unblinding of patients at 6 months.BackgroundThe blood pressure (BP)–lowering efficacy and safety of endovascular ultrasound renal denervation (RDN) in the absence (2 months) and presence (6 months) of antihypertensive medications were previously reported.MethodsPatients with daytime ambulatory BP ≥135/85 mm Hg after 4 weeks off medication were randomized to RDN (n = 74) or sham (n = 72) and maintained off medication for 2 months. A standardized medication escalation protocol was instituted between 2 and 5 months (blinded phase). Between 6 and 12 months (unblinded phase), patients received antihypertensive medications at physicians’ discretion. Outcomes at 12 months included medication burden, change in daytime ambulatory systolic BP (dASBP) and office or home systolic BP (SBP), visit-to-visit variability in SBP, and safety.ResultsSixty-five of 74 RDN patients and 67 of 72 sham patients had 12-month dASBP measurements. The proportion of patients on ≥2 medications (27.7% vs. 44.8%; p = 0.041), the number of medications (1.0 vs. 1.4; p = 0.015), and defined daily dose (1.4 vs. 2.2; p = 0.007) were less with RDN versus sham. The decrease in dASBP from baseline in the RDN group (−16.5 ± 12.9 mm Hg) remained stable at 12 months. The RDN versus sham adjusted difference at 12 months was −2.3 mm Hg (95% confidence interval [CI]: −5.9 to 1.3 mm Hg; p = 0.201) for dASBP, −6.3 mm Hg (95% CI: −11.1 to −1.5 mm Hg; p = 0.010) for office SBP, and −3.4 mm Hg (95% CI: −6.9 to 0.1 mm Hg; p = 0.062) for home SBP. Visit-to-visit variability in SBP was smaller in the RDN group. No renal artery injury was detected on computed tomographic or magnetic resonance angiography.ConclusionsDespite unblinding, the BP-lowering effect of RDN was maintained at 12 months with fewer prescribed medications compared with sham.     

Right-to-Left Shunt Through Iatrogenic Atrial Septal Defect After MitraClip Procedure

ObjectivesThe aim of this study was to investigate the incidence, characteristics, hemodynamic conditions, and clinical significance of right-to-left (R-L) shunt through an iatrogenic atrial septal defect (iASD) after the MitraClip procedure.BackgroundR-L shunt through an iASD after the MitraClip procedure has not been well investigated.MethodsFrom 2014 to 2017, 385 consecutive patients with mitral regurgitation underwent the MitraClip procedure. iASD was assessed using intraprocedural transesophageal echocardiography. Right and left heart catheterization was used to assess the hemodynamic status of patients. All patients provided written informed consent for the procedure. All data for this study were collected from an established interventional cardiology laboratory database approved by the Cedars-Sinai Medical Center Institutional Review Board.ResultsR-L shunt was observed in 20 patients (5%). In 7 of these patients (35%), R-L shunt was accompanied by acute deoxygenation. Prevalence of severe tricuspid regurgitation (55% vs. 20%; p = 0.001), serum B-type natriuretic peptide (664 pg/ml [434 to 1,169 pg/ml] vs. 400 pg/ml [195 to 699 pg/ml]; p = 0.006), mean pulmonary artery pressure (38 mm Hg [34 to 45 mm Hg] vs. 29 mm Hg [22 to 37 mm Hg]; p < 0.001), and right atrial pressure (19 mm Hg [13 to 20 mm Hg] vs. 10 mm Hg [7 to 14 mm Hg]; p < 0.001) were significantly higher in patients with R-L shunt than in those with left-to-right shunt. Patients with R-L shunt also showed a more prominent reduction in the left atrial V-wave and mean pressure from baseline to post-procedure compared with those with left-to-right shunt (−22.8 ± 2.6 mm Hg vs. −11.8 ± 0.9 mm Hg [p = 0.002] and −7.9 ± 0.8 mm Hg vs. −4.0 ± 0.4 mm Hg [p = 0.003], respectively).ConclusionsR-L shunt through an iASD was observed in 5% of patients who underwent the MitraClip procedure and in one-third of patients with R-L shunt presented acute deoxygenation. Elevated right atrial pressure concomitant with pulmonary hypertension and significant reduction in left atrial pressure after MitraClip deployment were associated with R-L shunt.     

Seasonal variation in estimated cardiovascular risk in patients with type 2 diabetes

Background and aimsSeasonal variations in several risk factors for cardiovascular events (CVD) were described. Here, we evaluate the impact of seasonal variations in blood pressure (BP), lipid profile and glycemic control on estimated CVD risk in patients with type 2 diabetes (T2D).Methods and resultsRetrospective monocentric study of patients with T2D who were visited at least once in the winter period and once in the summer period, less than 8 months apart, for which data related to systolic (S) BP, diastolic (D) BP, body mass index, glycosylated hemoglobin (HbA1c), total cholesterol, HDL cholesterol and smoking habit were available on both occasions. The 10-year CVD risk was calculated using the UKPDS risk engine and the ASCVD risk estimator. As many as 411 patients were included in the study. Significant within-patient differences between summer and winter were found for the absolute risk of events assessed with both calculators (Δs-w UKPDS-CHD: ?1.33%, Δs-w UKPDS-Stroke: ?0.84%, Δs-w ASCVD: ?2.21%). The seasonal change in SBP was the main responsible for the change in risk estimated with both the UKPDS-Stroke (r² = 0.43) and the ASCVD (r² = 0.50) scores, while the change in total cholesterol was the main determinant of the change in risk for the UKPDS-CHD (r² = 0.34). A significant correlation was identified between changes in temperature and changes in SBP (ρ = 0.130, p = 0.008), but not in other risk factors.ConclusionsSeasonal variations in the classic CVD risk factors influence the risk estimated using validated calculators.     

ACC/AHA Versus ESC/ESH on Hypertension Guidelines: JACC Guideline Comparison

This study compares the recommendations of the most recent American College of Cardiology (ACC)/American Heart Association (AHA) and European Society of Cardiology (ESC)/European Society of Hypertension (ESH) blood pressure guidelines. Both guidelines represent updates of previous guidelines and reinforce previous concepts of prevention regarding elevated blood pressure. Specifically, a low-sodium diet, exercise, body weight reduction, low to moderate alcohol intake, and adequate potassium intake are emphasized. Overall, both guidelines agree on the proper method of blood pressure measurement, the use of home blood pressure and ambulatory monitoring, and restricted use of beta-blockers as first-line therapy. The major disagreements are with the level of blood pressure defining hypertension, flexibility in identifying blood pressure targets for treatment, and the use of initial combination therapy. Although initial single-pill combination therapy is strongly recommended in both guidelines, the ESC/ESH guideline recommends it as initial therapy in patients at ≥140/90 mm Hg. The ACC/AHA guideline recommends its use in patients >20/10 mm Hg above blood pressure goal. Thus, the only real disagreement is that the ACC/AHA guidelines maintain that all people with blood pressure >130/80 mm Hg have hypertension, and blood pressure should be lowered to <130/80 mm Hg in all. In contrast, the ESC/ESH guidelines state that hypertension is defined as >140/90 mm Hg, with the goal being a level <140/90 mm Hg for all targeting to <130/80 mm Hg only in those at high cardiovascular risk, but always considering individual tolerability of the proposed goal.     

Sleep Irregularity and Risk of Cardiovascular Events: The Multi-Ethnic Study of Atherosclerosis

BackgroundThe cardiovascular system exhibits strong circadian rhythms to maintain normal functioning. Irregular sleep schedules, characterized by high day-to-day variability in sleep duration or timing, represent possibly milder but much more common and chronic disruption of circadian rhythms in the general population than shift work.ObjectivesThis study aimed to prospectively examine the association between sleep regularity and risk of cardiovascular disease (CVD).MethodsIn MESA (Multi-Ethnic Study of Atherosclerosis), 1,992 participants free of CVD completed 7-day wrist actigraphy for sleep assessment from 2010 to 2013 and were prospectively followed through 2016. The study assessed sleep regularity using the SD of actigraphy-measured sleep duration and sleep-onset timing across 7 days. Incident CVD included nonfatal and fatal cardiovascular events. A Cox proportional hazards model was used to estimate hazard ratios (HRs) for incident CVD according to SD of sleep duration and timing, adjusted for traditional CVD risk factors (including CVD biomarkers) and other sleep-related factors (including average sleep duration).ResultsDuring a median follow-up of 4.9 years, 111 participants developed CVD events. The multivariable-adjusted HRs (95% confidence intervals) for CVD across categories of sleep duration SD were 1.00 (reference) for ≤60 min, 1.09 (0.62 to 1.92) for 61 to 90 min, 1.59 (0.91 to 2.76) for 91 to 120 min, and 2.14 (1.24 to 3.68) for >120 min (p trend = 0.002). Similarly, compared with participants with a sleep timing SD ≤30 min, the HRs (95% confidence intervals) for CVD were 1.16 (0.64 to 2.13) for 31 to 60 min, 1.52 (0.81 to 2.88) for 61 to 90 min, and 2.11 (1.13 to 3.91) for >90 min (p trend = 0.002). Exclusion of current shift workers yielded similar results.ConclusionsIrregular sleep duration and timing may be novel risk factors for CVD, independent of traditional CVD risk factors and sleep quantity and/or quality.     

Lifetime risk of cardiovascular disease and life expectancy with and without cardiovascular disease according to changes in metabolic syndrome status

Background and aimsThe relationship between dynamic changes in metabolic syndrome (MetS) status and lifetime risk of cardiovascular disease (CVD) has not been reliably quantified. This study aimed to estimate lifetime risk of CVD and life expectancy with and without CVD according to dynamic MetS status.Methods and ResultsDynamic changes in MetS status were assessed: MetS-free, MetS-chronic, MetS-developed, and MetS-recovery groups. We used Modified Kaplan–Meier method to estimate lifetime risk and used multistate life table method to calculate life expectancy. Participants free of CVD at index ages 35 (n = 40 168), 45 (n = 33 569), and 55 (n = 18 546) years. At index age 35 years, we recorded 1341 CVD events during a median follow-up of 6.1 years. Lifetime risk of 33.9% (95% CI: 26.9%–41.0%) in MetS-recovery group was lower than that of 39.4% (95% CI: 36.1%–42.8%) in MetS-chronic group. Lifetime risk of 37.8% (95% CI: 30.6%–45.1%) in MetS-developed group was higher than that of 26.4% (95% CI: 22.7%–30.0%) in MetS-free group. At index age 35 years, life expectancy free of CVD for MetS-recovery group (44.1 years) was higher than that for MetS-chronic group (38.8 years). Life expectancy free of CVD for MetS-developed group (41.9 years) was lower than that for MetS-free group (46.7 years).ConclusionsRecovery from MetS was associated with decreased lifetime risk of CVD and a longer life expectancy free of CVD, whereas development of MetS was associated with increased lifetime risk of CVD and a shorter life expectancy free of CVD.     

Renal Denervation for Hypertension: A Systematic Review and Meta-Analysis of Randomized, Blinded,Placebo-Controlled Trials

ObjectivesThe authors performed an updated meta-analysis of randomized placebo-controlled trials of renal denervation and specifically compared the effect of renal denervation in patients taking medications and in those not taking medications.BackgroundRenal denervation has now undergone several blinded placebo-controlled trials, covering the spectrum from patients with drug-resistant hypertension to those not yet taking antihypertensive medications.MethodsAll blinded placebo-controlled randomized trials of catheter-based renal sympathetic denervation for hypertension were systematically identified, and a random-effects meta-analysis was performed. The primary efficacy outcome was the change in ambulatory systolic blood pressure beyond the effect of the placebo procedure. Analysis was stratified by whether there was background antihypertensive medication use.ResultsThere were 7 eligible trials, totaling 1,368 patients. Denervation significantly reduced ambulatory systolic (mean difference −3.61 mm Hg; 95% CI: −4.89 to –2.33 mm Hg; P < 0.0001), ambulatory diastolic (−1.85 mm Hg; 95% CI: −2.78 to −0.92 mm Hg; P < 0.0001), office systolic (−5.86 mm Hg; 95% CI: −7.77 to −3.94 mm Hg; P < 0.0001), and office diastolic (−3.63 mm Hg; 95% CI: −4.77 to −2.50; P < 0.0001) blood pressure. There was no evidence that the use of concomitant antihypertensive medication had a significant impact on the effect of denervation on any of these endpoints (P_interaction = NS for each comparison).ConclusionsThe randomized placebo-controlled trials show consistently that renal denervation provides significant reduction in ambulatory and office blood pressure. Although the magnitude of benefit, about 4/2 mm Hg, is modest, it is similar between patients on background antihypertensive medications and those who are not. Denervation could therefore be a useful strategy at various points for patients who are not willing to add antihypertensive agents. Whether the effect changes with time is currently unknown.     

Diastolic Blood Pressure and Heart Rate Are Independently Associated With Mortality in Chronic Aortic Regurgitation

BackgroundThe prognostic significance of diastolic blood pressure (DBP) and resting heart rate (RHR) in patients with hemodynamically significant aortic regurgitation (AR) is unknown.ObjectivesThis study sought to investigate the association of DBP and RHR with all-cause mortality in patients with AR.MethodsConsecutive patients with ≥ moderate to severe AR were retrospectively identified from 2006 to 2017. The association between all-cause mortality and routinely measured DBP and RHR was examined.ResultsOf 820 patients (age 59 ± 17 years; 82% men) followed for 5.5 ± 3.5 years, 104 died under medical management, and 400 underwent aortic valve surgery (AVS). Age, symptoms, left ventricular ejection fraction (LVEF), LV end-systolic diameter-index (LVESDi), DBP, and RHR were univariable predictors of all-cause mortality (all p ≤ 0.002). When adjusted for demographics, comorbidities, and surgical triggers (symptoms, LVEF, and LVESDi), baseline DBP (adjusted-hazard ratio [HR]: 0.79 [95% confidence interval: 0.66 to 0.94] per 10 mm Hg increase, p = 0.009) and baseline RHR (adjusted HR: 1.23 [95% confidence interval: 1.03 to 1.45] per 10 beat per min [bpm] increase, p = 0.01) were independently associated with all-cause mortality. These associations persisted after adjustment for presence of hypertension, medications, time-dependent AVS, and using average DBP and RHR (all p ≤ 0.02). Compared with the general population, patients with AR exhibited excess mortality (relative risk of death >1), which rose steeply in inverse proportion (p nonlinearity = 0.002) to DBP starting at 70 mm Hg and peaking at 55 mm Hg and in direct proportion to RHR starting at 60 bpm.ConclusionsIn patients with chronic hemodynamically significant AR, routinely measured DBP and RHR demonstrate a robust association with all-cause death, independent of demographics, comorbidities, guideline-based surgical triggers, presence of hypertension, and use of medications. Therefore, DBP and RHR should be integrated into comprehensive clinical decision-making for these patients.