Differences in the effectiveness and safety of different renal denervation devices.

Renal denervation (RDN) is a minimally invasive, endovascular catheter-based procedure using radiofrequency, ultrasound, or alcohol-mediated ablation to treat resistant hypertension. RDN gained popularity in 2009 when it was shown to have an antihypertensive effect. However, concerns about the efficacy of RDN were raised in the HTN-3 trial published in 2014, and the development of several RDN devices was then discontinued. In the process, new randomized controlled trials were conducted after the development of some of the RDN devices, the quality assurance of the procedure, changes in ablation points, and improvements in study design. In November 2023, the U.S. Food and Drug Administration approved a radiofrequency RDN device and an ultrasound RDN device. The results of a randomized controlled trial of an alcohol-mediated RDN device have been published, and future trends are being watched closely. In this mini-review, we summarize the differences in the antihypertensive effect and safety of the different RDN devices and the endpoints of the procedure in order to contribute to the further development of RDN devices Currently available renal denervation device. A multielectrode radiofrequency ablation (Spyral), (B) ultrasound denervation (Paraise), and (C) alcohol-mediated perivascular denervation (Peregrine). ASBP ambulatory systolic blood pressure, ADBP ambulatory diastolic blood pressure, OSBP office systolic blood pressure, ODBP office diastolic blood pressure. Analysis according to types of renal denervation device (radiofrequency, ultrasound, or alcohol-mediated device). P values for interaction were 0.578 (ambulatory SBP), 0.499 (ambulatory diastolic BP), 0.853 (office SBP), and 0.870 (office diastolic BP).

Effects of renal denervation on blood pressure in patients with hypertension: a latest systematic review and meta-analysis of randomized sham-controlled trials.

The efficacy of renal denervation (RDN) has been controversial, but recent randomized sham-controlled trials demonstrated significant blood pressure reductions after RDN in patients with hypertension. We conducted a systematic review and updated meta-analysis to evaluate the effects of RDN on ambulatory and office blood pressures in patients with hypertension. Databases were searched up to 15 November 2023 to identify randomized, sham-controlled trials of RDN. The primary endpoint was change in 24 h ambulatory systolic blood pressure (SBP) with RDN versus sham control. The secondary endpoints were changes in 24 h ambulatory diastolic blood pressure, daytime and nighttime blood pressure (BP), office BP, and home BP. A sub-analysis determined outcomes by medication, procedure, and device. From twelve trials, 2222 patients with hypertension were randomized to undergo RDN (n = 1295) or a sham procedure (n = 927). At 2-6 months after treatment, RDN significantly reduced 24 h ambulatory SBP by 2.81 mmHg (95% confidence interval: -4.09, -1.53; p < 0.001) compared with the sham procedure. RDN also reduced daytime SBP by 3.17 mmHg (- 4.75, - 1.58; p < 0.001), nighttime SBP by 3.41 mmHg (- 4.69, - 2.13; p < 0.001), office SBP by 4.95 mmHg (- 6.37, - 3.54; p < 0.001), and home SBP by 4.64 mmHg (- 7.44, - 1.84; p = 0.001) versus the sham control group. There were no significant differences in the magnitude of BP reduction between first- and second-generation trials, between devices, or between with or without medication. These data from randomized sham-controlled trials showed that RDN significantly reduced all blood pressure metrics in medicated or unmedicated patients with hypertension, including resistant/uncontrolled hypertension.

Inconsistent Control Status of Office, Home, and Ambulatory Blood Pressure All Taken Using the Same Device: The HI-JAMP Study Baseline Data.

BACKGROUND: Inconsistencies between the office and out-of-office blood pressure (BP) values (described as white-coat hypertension or masked hypertension) may be attributable in part to differences in the BP monitoring devices used. METHODS: We studied consistency in the classification of BP control (well-controlled BP vs. uncontrolled BP) among office, home, and ambulatory BPs by using a validated "all-in-one" BP monitoring device. In the nationwide, general practitioner-based multicenter HI-JAMP study, 2,322 hypertensive patients treated with antihypertensive drugs underwent office BP measurements and 24-hour ambulatory BP monitoring (ABPM), consecutively followed by 5-day home BP monitoring (HBPM), for a total of seven BP measurement days. RESULTS: Using the thresholds of the JSH2019 and ESC2018 guidelines, the patients with consistent classification of well-controlled status in the office (<140 mmHg) and home systolic BP (SBP) (<135 mmHg) (n = 970) also tended to have well-controlled 24-hour SBP (<130 mmHg) (n = 808, 83.3%). The patients with the consistent classification of uncontrolled status in office and home SBP (n = 579) also tended to have uncontrolled 24-hour SBP (n = 444, 80.9%). Among the patients with inconsistent classifications of office and home BP control (n = 803), 46.1% had inconsistent ABPM-vs.-HBPM out-of-office BP control status. When the 2017 ACC/AHA thresholds were applied as an alternative, the results were essentially the same. CONCLUSIONS: The combined assessment of the office and home BP is useful in clinical practice. Especially for patients whose office BP classification and home BP classification conflict, the complementary clinical use of both HBPM and ABPM might be recommended.

Catheter-based ultrasound renal denervation in patients with resistant hypertension: the randomized, controlled REQUIRE trial.

Renal denervation is a promising new non-pharmacological treatment for resistant hypertension. However, there is a lack of data from Asian patients. The REQUIRE trial investigated the blood pressure-lowering efficacy of renal denervation in treated patients with resistant hypertension from Japan and South Korea. Adults with resistant hypertension (seated office blood pressure ≥150/90 mmHg and 24-hour ambulatory systolic blood pressure ≥140 mmHg) with suitable renal artery anatomy were randomized to ultrasound renal denervation or a sham procedure. The primary endpoint was change from baseline in 24-hour ambulatory systolic blood pressure at 3 months. A total of 143 patients were included (72 renal denervation, 71 sham control). Reduction from baseline in 24-hour ambulatory systolic blood pressure at 3 months was not significantly different between the renal denervation (-6.6 mmHg) and sham control (-6.5 mmHg) groups (difference: -0.1, 95% confidence interval -5.5, 5.3; p = 0.971). Reductions from baseline in home and office systolic blood pressure (differences: -1.8 mmHg [p = 0.488] and -2.0 mmHg [p = 0.511], respectively), and medication load, did not differ significantly between the two groups. The procedure-/device-related major adverse events was not seen. This study did not show a significant difference in ambulatory blood pressure reductions between renal denervation and a sham procedure in treated patients with resistant hypertension. Although blood pressure reduction after renal denervation was similar to other sham-controlled studies, the sham group in this study showed much greater reduction. This unexpected blood pressure reduction in the sham control group highlights study design issues that will be addressed in a new trial. CLINICAL TRIAL REGISTRATION: NCT02918305 ( http://www.clinicaltrials.gov ).

Effects of renal denervation on blood pressures in patients with hypertension: a systematic review and meta-analysis of randomized sham-controlled trials.

The efficacy of renal denervation has been controversial, but recent randomized sham-controlled trials demonstrated significant blood pressure reductions after renal denervation in patients with hypertension. We conducted a systematic review and updated meta-analysis to evaluate the effects of renal denervation on ambulatory and office blood pressures in patients with hypertension. Databases were searched up to 25 May 2021 to identify randomized, sham-controlled trials of renal denervation. The primary endpoint was change in 24 h ambulatory systolic blood pressure with renal denervation versus sham control. The secondary endpoints were daytime and nighttime systolic blood pressure, and office systolic blood pressure. A sub-analysis determined outcomes by medication, procedure, and device. From nine trials, 1555 patients with hypertension were randomized to undergo renal denervation (n = 885) or a sham procedure (n = 670). At 2-6 months after treatment, renal denervation significantly reduced 24 h ambulatory systolic blood pressure by 3.31 mmHg (95% confidence interval: -4.69, -1.94) compared with the sham procedure (p < 0.001). Renal denervation also reduced daytime SBP by 3.53 mmHg (-5.28, -1.78; p < 0.001), nighttime SBP by 3.20 mmHg (-5.46, -0.94; p = 0.006), and office SBP by 5.25 mmHg (-7.09, -3.40; p < 0.001) versus the sham control group. There were no significant differences in the magnitude of blood pressure reduction between first- and second-generation trials, between devices, or with or without medication. These data from randomized sham-controlled trials showed that renal denervation significantly reduced all blood pressure metrics in medicated or unmedicated patients with hypertension, including resistant/uncontrolled hypertension. Future trials should investigate the long-term efficacy and safety of renal denervation.

Renal denervation based on experimental rationale.

Excessive activation of the sympathetic nervous system is one of the pathophysiological hallmarks of hypertension and heart failure. Within the central nervous system, the paraventricular nucleus (PVN) of the hypothalamus and the rostral ventrolateral medulla in the brain stem play critical roles in the regulation of sympathetic outflow to peripheral organs. Information from the peripheral circulation, including serum concentrations of sodium and angiotensin II, is conveyed to the PVN via adjacent structures with a weak blood-brain barrier. In addition, signals from baroreceptors, chemoreceptors and cardiopulmonary receptors as well as afferent input via the renal nerves are all integrated at the level of the PVN. The brain renin-angiotensin system and the balance between nitric oxide and reactive oxygen species in these brain areas also determine the final sympathetic outflow. Additionally, brain inflammatory responses have been shown to modulate these processes. Renal denervation interrupts both the afferent inputs from the kidney to the PVN and the efferent outputs from the PVN to the kidney, resulting in the suppression of sympathetic outflow and eliciting beneficial effects on both hypertension and heart failure.

The Combination of Non-dipper Heart Rate and High Brain Natriuretic Peptide Predicts Cardiovascular Events: The Japan Morning Surge-Home Blood Pressure (J-HOP) Study.

BACKGROUND: We hypothesized that the association between the dipping heart rate (HR) pattern and cardiovascular (CV) events differs according to the brain natriuretic peptide (BNP) level. METHODS: We examined a subgroup of 1,369 patients from the Japan Morning Surge Home Blood Pressure study; these were patients who had CV risk factors and had undergone ambulatory blood pressure (BP) monitoring. HR non-dipping status was defined as (awake HR - sleep HR)/awake HR <0.1, and high BNP was defined as ≥35 pg/ml. We divided the patients into four groups according to their HR dipper status (dipping or non-dipping) and BNP level (normal or high). RESULTS: The mean follow-up period was 60 ± 30 months. The primary endpoints were fatal/nonfatal CV events (myocardial infarction, angina pectoris, stroke, hospitalization for heart failure, and aortic dissection). During the follow-up period, 23 patients (2.8%) in the dipper HR with normal BNP group, 8 patients (4.4%) in the non-dipper HR with normal BNP group, 24 patients (9.5%) in the dipper HR with high-BNP group, and 25 patients (21.0%) in the non-dipper HR with high-BNP group suffered primary endpoints (log rank 78.8, P < 0.001). Non-dipper HR was revealed as an independent predictor of CV events (hazard ratio, 2.13; 95% confidence interval, 1.35-3.36; P = 0.001) after adjusting for age, gender and smoking, dyslipidemia, diabetes mellitus, chronic kidney disease, BNP, non-dipper BP, 24-h HR, and 24-h systolic blood pressure. CONCLUSIONS: The combination of non-dipper HR and higher BNP was associated with a higher incidence of CV events.

Comparison of Morphological Patterns Between In-Stent Restenosis Lesions of Overlapping and Non-Overlapping Second- and Third-Generation Stents Using Optical Frequency Domain Imaging.

PURPOSE: To analyze the difference in morphological patterns between in-stent restenosis (ISR) lesions of overlapping segments and ISR lesions of non-overlapping segments with second- and third-generation drug-eluting stents (DESs) using optical frequency domain imaging (OFDI). METHODS: We analyzed 23 consecutive ISR lesions after second- or third-generation DES implantation using OFDI. RESULTS: A total of 18 men and 5 women (median age, 68.0 years; interquartile range, 51.0-74.0 years) were included in the analysis. Fourteen and nine patients underwent second- and third-generation DES implantation, respectively. The median ISR detection timepoint was 10.0 months after implantation (interquartile range, 9.0-34.0 months). In 9 out of 23 lesions, ISR was found in the stent overlap area (overlapping segment group); the remaining 14 cases were categorized as the non-overlapping segment group. In OFDI analysis, homogeneous, layered, and heterogeneous patterns were found in 22%, 55%, and 22%, respectively, of lesions in the overlapping segment group and 14%, 50%, and 35%, respectively, of lesions in the non-overlapping segment group. There was no difference in the distribution of restenotic tissue structure patterns between the groups (p = .756). CONCLUSIONS: Morphological assessments of ISR tissue using OFDI showed no difference between the overlapping and non-overlapping segment groups with second and third-generation DESs in this hypothesis generating study.

Evaluation of stent length on the outcome of ST-segment elevation myocardial infarction receiving primary percutaneous coronary intervention.

BACKGROUND: A longer stent length is known to be a predictor of adverse events after a percutaneous coronary intervention (PCI). However, the evaluation of the stent length on the outcome of ST-segment elevation myocardial infarction (STEMI) patients is not enough. PATIENTS AND METHODS: A total of 686 STEMI patients who underwent primary PCI were divided into four groups according to the total stent length as follows: short (<18 mm, n=183), lower-medium (18-23 mm, n=256), upper-medium (24-31 mm, n=155), and long (≥32 mm, n=92). We compared the all-cause mortality, major adverse cardiovascular events (MACEs; composite of cardiovascular death, myocardial infarction, and stroke after discharge), target lesion revascularization, and target vessel revascularization with a median follow-up of 1213 days among these four groups. RESULTS: There were no significant differences in MACEs (10.4% in the short, 7.0% in the lower-medium, 6.5% in the upper-medium, 7.6% in the long, P=0.633) among the different stent length groups. The all-cause mortality, target lesion revascularization, and target vessel revascularization also did not differ among the four groups. In the drug-eluting stent (n=237) and bare-metal stent subgroups (n=449), all outcomes were comparable among the groups. However, in the diabetes subgroup (n=265), the rate of MACEs was higher in the long group than in the other groups, although the difference was not significant (6.6% in the short, 9.6% in the lower-medium, 3.4% in upper-medium, 16.7% in long group, P=0.095). CONCLUSION: A long stent length was not associated with adverse clinical outcomes in STEMI patients who underwent primary PCI.

Outcome of staged percutaneous coronary intervention within two weeks from admission in patients with ST-segment elevation myocardial infarction with multivessel disease.

BACKGROUND: The optimum timing of revascularization strategy for stenoses in nonculprit vessels in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel disease (MVD) remains unclear. At present, there is no evidence investigating the outcome of staged percutaneous coronary intervention (PCI) within two weeks from admission among STEMI patients with MVD. METHODS: A total of 210 STEMI patients with MVD who underwent primary PCI were analyzed. We compared the all-cause mortality and major adverse cardiovascular events (MACE) (cardiovascular death, myocardial infarction, heart failure, unstable angina, and stroke) with median follow-up of 1200 days among the patients who underwent staged PCI within two weeks from admission (staged PCI ≤2 W) (n = 75), staged PCI after two weeks from admission (staged PCI >2 W) (n = 37) and culprit-only PCI (n = 98) in patients with STEMI and MVD. RESULTS: The staged PCI ≤2 W showed lower all-cause mortality than culprit-only PCI (4.0 vs 29.6%, log-rank P = 0.001), and lower incidence of MACE than the staged PCI >2 W group (1.3 vs 18.9%, log-rank P = 0.001) and culprit-only PCI group (1.3 vs 22.5%, log-rank P = 0.001). In the multivariable Cox regression analysis, the staged PCI ≤2 W was a predictor of lower all-cause mortality (hazard ratio [HR], 0.176; 95% confidence interval [CI], 0.049-0.630; P = 0.008) and lower incidence of MACE (HR, 0.068; 95% CI, 0.009-0.533; P = 0.011), but staged PCI >2 W was not. CONCLUSION: In conclusion, staged PCI within two weeks after admission showed more favorable outcomes compared with staged PCI after two weeks from admission or culprit-only PCI in STEMI patients with MVD.

Successful hybrid treatment with endovascular aorto-iliac revascularization and coronary bypass surgery in a patient with an advanced complex polyvascular disease.

A 72-year-old Japanese man was admitted to our hospital for effort chest pain and bilateral claudication. He was diagnosed as having severe ischemic heart disease and chronic bilateral aorto-iliac occlusions (Leriche syndrome) by a diagnostic angiography. Manifest collaterals via bilateral internal thoracic arteries (ITA) supplied sufficient blood flow for his lower limbs. We planned a two-stage operation for both the severe coronary artery disease and peripheral artery occlusive disease. He first underwent endovascular therapy (EVT) for bilateral aorto-iliac occlusion. One month later he underwent coronary artery bypass grafting (CABG) that was carried out for three coronary arteries with bilateral ITAs, also known as the internal thoracic artery, and the gastroepiploic artery. His chest symptoms and claudication were completely relieved and he was discharged uneventfully. We hereby suggest that EVT can be a safe, effective, and minimally invasive treatment to enable the patient to undergo CABG with all arterial grafts. .

S100A12 as a marker to predict cardiovascular events in patients with chronic coronary artery disease.

BACKGROUND: S100A12, a calgranulin family protein released from white blood cells, is involved in inflammatory cardiovascular disease. It was hypothesized that the plasma level of S100A12 can be used to predict outcome in patients with chronic coronary artery disease (CAD). The purpose of this study was to clarify the clinical significance of S100A12 in patients with stable CAD. METHODS AND RESULTS: A total of 652 patients with stable CAD were studied. All patients underwent percutaneous coronary intervention and successful revascularization. Major adverse cardiovascular events (MACE) were defined as a composite of events of CHF, recurrence of angina pectoris, acute myocardial infarction, stroke, critical arrhythmia, intervention to peripheral arteries and cardiac death. The mean follow-up period was 973±639 days. MACE occurred in 108 patients (16.6%). Plasma S100A12 level had a significant positive correlation with high-sensitivity C-reactive protein (hs-CRP) level. On Kaplan-Meier curve analysis the incidence of MACE was significantly different among S100A12 quartiles (P=0.026). The highest S100A12 quartile (Q4) had a significantly higher MACE rate than the lowest quartile (Q1) (P=0.002). In contrast, hs-CRP was not significant for predicting MACE in the present subjects (P=0.074). A Cox proportional hazard model showed that S100A12 was an independent factor for predicting MACE in multivariate models. CONCLUSIONS: S100A12 could be a novel biomarker for predicting cardiovascular events for predicting MACE in patients with stable CAD.