Durability of blood pressure reduction after ultrasound renal denervation: three-year follow-up of the treatment arm of the randomised RADIANCE-HTN SOLO trial.

BACKGROUND: While the blood pressure (BP)-lowering effect of renal denervation (RDN) has been established, long-term durability is a key prerequisite for a broader clinical implementation. AIMS: Our aims were to assess the long-term durability of the office BP (OBP)-lowering efficacy, antihypertensive medication (AHM) use, and safety of ultrasound RDN (uRDN). METHODS: Four weeks after withdrawal of AHM, patients with untreated daytime ambulatory BP ≥135/85 mmHg and <170/105 mmHg were randomised to uRDN (n=74) or sham (n=72) in the RADIANCE-HTN SOLO trial. Initiation of AHM was encouraged for home BP >135/85 mmHg following primary endpoint ascertainment at 2 months. Patients and physicians were unblinded at 6 months.  Results: Fifty-one of 74 patients (age: 53.9±11 years; 67% men) originally randomised to uRDN completed the 36-month follow-up. Initial screening OBP upon study entry was 145/92±14/10 mmHg on a mean of 1.2 AHM (range: 0-2.0). Baseline OBP after AHM washout was 154/99±13/8 mmHg. At 36 months, patients were on an average of 1.3 AHM (range: 0-3.0) with 8 patients on no AHM. OBP decreased by 18/11±15/9 mmHg from baseline to 36 months (p<0.001 for both). Overall, OBP control (<140/90 mmHg) improved from 29.4% at screening to 45.1% at 36 months (p=0.059). For patients uncontrolled at screening (n=36), systolic OBP decreased by 10.8 mmHg (p<0.001) at 36 months on similar AHM (p=0.158). CONCLUSIONS: The safety and effectiveness of uRDN was durable to 36 months, with reduced OBP and improved OBP control despite a similar starting medication burden. No new uRDN-related long-term safety concerns were identified.

Changes in blood pressure after crossover to ultrasound renal denervation in patients initially treated with sham in the RADIANCE-HTN SOLO trial.

BACKGROUND: The multicentre, randomised, sham-controlled RADIANCE-HTN SOLO trial reported the blood pressure (BP)-lowering efficacy and safety of ultrasound renal denervation (RDN) in the absence (2 months) and presence (6 and 12 months) of antihypertensive medications in patients with mild-to-moderate hypertension. AIMS: The aim of this report was to evaluate patients originally assigned to the sham group who crossed over to RDN. METHODS: After the primary endpoint was met, patients in the sham arm who remained uncontrolled were allowed to cross over to receive RDN. All patients were unblinded and treated with standard of care medications at the time of crossover. Ambulatory BP was evaluated 2 and 6 months after crossover. RESULTS: Among 72 subjects of the sham arm, 33 underwent ultrasound RDN after an average follow-up of 23±6 months. Prior to crossover, patients had a daytime ambulatory BP of 144.1±10.1/89.9±8.4 mmHg and received 1.2±0.8 antihypertensive medications. Mean change in daytime ambulatory BP from pre-crossover to 2 and 6 months post RDN was -11.2±13.7/-7.1±8.9 mmHg (n=33; p<0.001; p<0.001) and -10.8±17.3/-7.8±11.6 mmHg (n=27; p=0.002; p<0.001). The number of antihypertensive medications did not change from pre-crossover baseline to 2 and 6 months. Eighteen of 33 (54.5%) patients had their daytime ambulatory BP controlled (<135/85 mmHg) at 2 months and 44.4% (12/27) at 6 months post RDN. No major procedure-related adverse events occurred. CONCLUSIONS: During unblinded long-term follow-up of the RADIANCE-HTN SOLO study, patients originally assigned to a sham procedure who remained uncontrolled had significant reductions in BP following crossover treatment with ultrasound RDN.

The CAPTURE registry: analysis of strokes resulting from carotid artery stenting in the post approval setting: timing, location, severity, and type.

BACKGROUND: Although previous reports of carotid stenting with embolic protection (CAS) have focused on clinical outcomes of death, stroke and myocardial infarction, there are few data available characterizing the strokes that occur during CAS, thus limiting understanding of potential mechanisms. This report examines the timing, location, severity, and type of strokes occurring with CAS in the Carotid ACCULINK/ACCUNET Post Approval Trial to Uncover Unanticipated or Rare Events (CAPTURE) study. METHODS: The CAPTURE is a prospective, multicenter registry conducted to assess outcomes of CAS in the postapproval setting after device approval. A neurologist examined the patients before the procedure, at 24 hours and 30 days post-procedure. The primary end point was a composite of death, any stroke, or myocardial infarction within 30 days post-procedure. Strokes and all neurologic events suspected to be strokes were adjudicated by an independent Clinical Events Adjudication Committee using prespecified definitions. Source documents of all patients with strokes in this cohort were reviewed. RESULTS: The 30-day results were available for 3500 patients. The 30-day primary end point event rate of death, stroke, and myocardial infarction was 6.3% (95% confidence interval: 5.5%-7.1%), and the rate of major stroke and death was 2.9% (95% confidence interval: 2.4 to 3.5). 4.8% of patients experienced a stroke (3.9% ipsilateral and 0.9% nonipsilateral, 2% major). A majority of stroke symptoms (57.7%) were noted post-procedure and pre-discharge, whereas 22.3% were noted during the procedure and 20% postdischarge. A similar timing distribution regardless of preprocedural symptomatic status was found.Overall, 41% (69 of 170) of all strokes were major. The incidence of major strokes was statistically significantly greater among symptomatic compared with asymptomatic patients, 4.6% (22 of 482) and 1.6% (47 of 3018), respectively. There were more minor than major strokes in asymptomatic patients (63% vs. 37%; P=0.10), whereas stroke severity was equally distributed in symptomatic patients. Among the ipsilateral strokes, almost half (44%) were major, whereas only one-quarter (26%) of the nonipsilateral strokes were major.Overall, 23% of the major strokes were hemorrhagic and 94% of these strokes were noted on the ipsilateral side. There was a tendency toward more major hemorrhagic strokes in symptomatic than in asymptomatic patients (36% vs. 17%; P=0.07). Fifty-four percent of the strokes post-procedure and pre-discharge were major, whereas 27% of the strokes postdischarge were major. Furthermore, 65% of hemorrhagic strokes were noted post-procedure and pre-discharge, 30% postdischarge. CONCLUSIONS: Strokes related to CAS seem to become clinically apparent after the procedure but before discharge in the majority of events. Nevertheless, a significant minority of stroke symptoms follows discharge from the hospital, typically after 24 hours. Timing of stroke after CAS seems to be similar to timing of stroke after carotid endarterectomy. Moreover, nearly 1 in 5 strokes occur in a nonipsilateral distribution, with the exception of intraprocedural events, which were all ipsilateral to the stent being implanted. Hemorrhagic stroke seemed to be more prevalent in the strokes occurring in the post-procedure period. These descriptors of stroke severity, location, and timing may provide insight in to the mechanistic causes of adverse neurologic outcomes in CAS.

Contextual fear conditioning is associated with lateralized expression of the immediate early gene c-fos in the central and basolateral amygdalar nuclei.

Fos, the protein product of the immediate early gene c-fos, was used to map functional circuitry underlying contextual conditioned fear. Male rats were given footshocks in a distinctive context and later tested using freezing as the behavioral measure and compared with no-shock and no-retention-test control groups. An increased number of Fos-immunoreactive neurons was found in the lateral part of the central nucleus and in the anterior basolateral and lateral amygdalar nuclei in the brains of the conditioned-fear group compared with controls. Further, a greater number of Fos-immunoreactive neurons was observed in the right central and anterior basolateral nuclei compared with the number of labeled neurons in these structures on the left.