Central arteriovenous anastomosis to treat resistant hypertension.

PURPOSE OF REVIEW: Novel, interventional treatments have emerged in the last decade for the treatment of resistant hypertension. This review focuses on a unique device that creates a fixed calibre, central iliac arteriovenous anastomosis that is significantly different in haemodynamic and safety profile from traditional haemodialysis fistulae. The background, physiology, and clinical data to date will be presented. RECENT FINDINGS: The single, randomized, controlled clinical trial using the ROX coupler in patients with resistant hypertension demonstrated substantial reductions in both office and ambulatory blood pressure to 12-month postimplantation. There was a common, but manageable, adverse effect of upstream iliac venous stenosis causing ipsilateral lower limb oedema. There were no renal safety concerns. The mechanism of action is proposed to be mechanical by provision of a low-pressure parallel circuit attached to the high-pressure arterial system though detailed physiological evaluation is currently lacking. SUMMARY: Preliminary data using the ROX coupler to form a central arteriovenous anastomosis are very encouraging. Concerns regarding the lack of sham control are to some extent mitigated by immediate on table blood pressure reduction with opening of the coupler and will be further addressed in the ongoing pivotal, sham-controlled ROX CONTROL Hypertension2 study which should provide further robust information regarding efficacy and safety.

Catheter-Based Renal Denervation for Hypertension.

PURPOSE OF REVIEW: This review was undertaken to update readers on the field of therapeutic renal denervation for hypertension during the 2016 through 2018 period. RECENT FINDINGS: After the failure of Symplicity HTN-3 to meet its top line objective, intense scrutiny revealed several possible concerns addressed by the newer investigations into the area of renal denervation. These included better device technology, more intense subject monitoring for off-protocol antihypertensive drug usage, and deeper penetration into the renal vasculature by the interventionist. Whether untreated by medication for hypertension or on antihypertensive medication, renal denervation shows a clear, though moderate, blood pressure reduction. The failure of roughly one out of three patients with hypertension to respond to denervation procedures argues that there is room for improvement in choosing the optimal patient for this approach to hypertension management.

Selective vs. Global Renal Denervation: a Case for Less Is More.

PURPOSE OF REVIEW: Review the renal nerve anatomy and physiology basics and explore the concept of global vs. selective renal denervation (RDN) to uncover some of the fundamental limitations of non-targeted renal nerve ablation and the potential superiority of selective RDN. RECENT FINDINGS: Recent trials testing the efficacy of RDN showed mixed results. Initial investigations targeted global RDN as a therapeutic goal. The repeat observation of heterogeneous response to RDN including non-responders with lack of a BP reduction, or even more unsettling, BP elevations after RDN has raised concern for the detrimental effects of unselective global RDN. Subsequent studies have suggested the presence of a heterogeneous fiber population and the potential utility of renal nerve stimulation to identify sympatho-stimulatory fibers or "hot spots." The recognition that RDN can produce heterogeneous afferent sympathetic effects both change therapeutic goals and revitalize the potential of therapeutic RDN to provide significant clinical benefits. Renal nerve stimulation has emerged as potential tool to identify sympatho-stimulatory fibers, avoid sympatho-inhibitory fibers, and thus guide selective RDN.

Percutaneous Creation of a Central Iliac Arteriovenous Anastomosis for the Treatment of Arterial Hypertension.

PURPOSE OF REVIEW: Provision of a summary on the physiologic effects of arteriovenous fistula creation and description of previously published human data on the efficacy of a percutaneously implanted device creating an arteriovenous fistula. Though antihypertensive therapy is effective, some patient's blood pressure remains poorly controlled despite adherence to optimal medical therapy. Moreover, some patients are not compliant with recommended medical therapy due to side effects or personal decision. This has prompted exploration of alternative, device-based antihypertensive therapies including, among others, the percutaneous creation of an arteriovenous fistula. An arteriovenous fistula is accompanied by a number of favorable physiologic changes that may lower blood pressure. These physiologic changes, conduction of the procedure, and previously published human experience are summarized in this review article. RECENT FINDINGS: The results of a recently published trial comparing arteriovenous fistula creation and standard antihypertensive therapy versus standard antihypertensive therapy alone are summarized. Creation of an arteriovenous fistula is accompanied by a significant blood pressure reduction likely related to a reduction in total arterial resistance, perhaps blood volume reduction, inhibition of the baroreceptor reflex, and release of natriuretic peptides. These findings foster further interest in studying the impact of an arteriovenous fistula and arterial blood pressure. The design of a large randomized trial comparing arteriovenous fistula creation to sham control is outlined.

Correction to: Percutaneous Creation of a Central Iliac Arteriovenous Anastomosis for the Treatment of Arterial Hypertension.

In the March 2018 issue of Current Hypertension Reports, the second author's name Nathan A. Sobotka was inadvertently left out of the byline. Also, the author names were changed from initials to spelled out. The corrected author list is given above. The original article has been corrected.

Interventional procedures and future drug therapy for hypertension.

Hypertension management poses a major challenge to clinicians globally once non-drug (lifestyle) measures have failed to control blood pressure (BP). Although drug treatment strategies to lower BP are well described, poor control rates of hypertension, even in the first world, suggest that more needs to be done to surmount the problem. A major issue is non-adherence to antihypertensive drugs, which is caused in part by drug intolerance due to side effects. More effective antihypertensive drugs are therefore required which have excellent tolerability and safety profiles in addition to being efficacious. For those patients who either do not tolerate or wish to take medication for hypertension or in whom BP control is not attained despite multiple antihypertensives, a novel class of interventional procedures to manage hypertension has emerged. While most of these target various aspects of the sympathetic nervous system regulation of BP, an additional procedure is now available, which addresses mechanical aspects of the circulation. Most of these new devices are supported by early and encouraging evidence for both safety and efficacy, although it is clear that more rigorous randomized controlled trial data will be essential before any of the technologies can be adopted as a standard of care.

Central arteriovenous anastomosis for the treatment of patients with uncontrolled hypertension (the ROX CONTROL HTN study): a randomised controlled trial.

BACKGROUND: Hypertension contributes to cardiovascular morbidity and mortality. We assessed the safety and efficacy of a central iliac arteriovenous anastomosis to alter the mechanical arterial properties and reduce blood pressure in patients with uncontrolled hypertension. METHODS: We enrolled patients in this open-label, multicentre, prospective, randomised, controlled trial between October, 2012, and April, 2014. Eligible patients had baseline office systolic blood pressure of 140 mm Hg or higher and average daytime ambulatory blood pressure of 135 mm Hg or higher systolic and 85 mm Hg or higher diastolic despite antihypertensive treatment. Patients were randomly allocated in a 1:1 ratio to undergo implantation of an arteriovenous coupler device plus current pharmaceutical treatment or to maintain current treatment alone (control). The primary endpoint was mean change from baseline in office and 24 h ambulatory systolic blood pressure at 6 months. Analysis was by modified intention to treat (all patients remaining in follow-up at 6 months). This trial is registered with ClinicalTrials.gov, number NCT01642498. FINDINGS: 83 (43%) of 195 patients screened were assigned arteriovenous coupler therapy (n=44) or normal care (n=39). Mean office systolic blood pressure reduced by 26·9 (SD 23·9) mm Hg in the arteriovenous coupler group (p<0·0001) and by 3·7 (21·2) mm Hg in the control group (p=0·31). Mean systolic 24 h ambulatory blood pressure reduced by 13·5 (18·8) mm Hg (p<0·0001) in arteriovenous coupler recipients and by 0·5 (15·8) mm Hg (p=0·86) in controls. Implantation of the arteriovenous coupler was associated with late ipsilateral venous stenosis in 12 (29%) of 42 patients and was treatable with venoplasty or stenting. INTERPRETATION: Arteriovenous anastomosis was associated with significantly reduced blood pressure and hypertensive complications. This approach might be a useful adjunctive therapy for patients with uncontrolled hypertension. FUNDING: ROX Medical.

Predictors of blood pressure response in the SYMPLICITY HTN-3 trial.

AIMS: The SYMPLICITY HTN-3 randomized, blinded, sham-controlled trial confirmed the safety of renal denervation (RDN), but did not meet its primary efficacy endpoint. Prior RDN studies have demonstrated significant and durable reductions in blood pressure. This analysis investigated factors that may help explain these disparate results. METHODS AND RESULTS: Patients with resistant hypertension were randomized 2 : 1 to RDN (n = 364) or sham (n = 171). The primary endpoint was the difference in office systolic blood pressure (SBP) change at 6 months. A multivariable analysis identified predictors of SBP change. Additional analyses examined the influence of medication changes, results in selected subgroups and procedural factors. Between randomization and the 6-month endpoint, 39% of patients underwent medication changes. Predictors of office SBP reduction at 6 months were baseline office SBP ≥ 180 mmHg, aldosterone antagonist use, and non-use of vasodilators; number of ablations was a predictor in the RDN group. Non-African-American patients receiving RDN had a significantly greater change in office SBP than those receiving sham; -15.2 ± 23.5 vs. -8.6 ± 24.8 mmHg, respectively (P = 0.012). Greater reductions in office and ambulatory SBP, and heart rate were observed with a higher number of ablations and energy delivery in a four-quadrant pattern. CONCLUSIONS: Post hoc analyses, although derived from limited patient cohorts, reveal several potential confounding factors that may partially explain the unexpected blood pressure responses in both the sham control and RDN groups. These hypothesis-generating data further inform the design of subsequent research to evaluate the potential role of RDN in the treatment of resistant hypertension. CLINICALTRIALS.GOV IDENTIFIER: NCT01418261.

Percutaneous renal denervation in patients with treatment-resistant hypertension: final 3-year report of the Symplicity HTN-1 study.

BACKGROUND: Renal denervation (RDN) with radiofrequency ablation substantially reduces blood pressure in patients with treatment-resistant hypertension. We assessed the long-term antihypertensive effects and safety. METHODS: Symplicity HTN-1 is an open-label study that enrolled 153 patients, of whom 111 consented to follow-up for 36 months. Eligible patients had a systolic blood pressure of at least 160 mm Hg and were taking at least three antihypertensive drugs, including a diuretic, at the optimum doses. Changes in office systolic blood pressure and safety were assessed every 6 months and reported every 12 months. This study is registered with ClinicalTrials.gov, numbers NCT00483808, NCT00664638, and NCT00753285. FINDINGS: 88 patients had complete data at 36 months. At baseline the mean age was 57 (SD 11) years, 37 (42%) patients were women, 25 (28%) had type 2 diabetes mellitus, the mean estimated glomerular filtration rate was 85 (SD 19) mL/min per 1·73 m(2), and mean blood pressure was 175/98 (SD 16/14) mm Hg. At 36 months significant changes were seen in systolic (-32·0 mm Hg, 95% CI -35·7 to -28·2) and diastolic blood pressure (-14·4 mm Hg, -16·9 to -11·9). Drops of 10 mm Hg or more in systolic blood pressure were seen in 69% of patients at 1 month, 81% at 6 months, 85% at 12 months, 83% at 24 months, and 93% at 36 months. One new renal artery stenosis requiring stenting and three deaths unrelated to RDN occurred during follow-up. INTERPRETATION: Changes in blood pressure after RDN persist long term in patients with treatment-resistant hypertension, with good safety. FUNDING: Ardian LLC/Medtronic Inc.

The ROX coupler: creation of a fixed iliac arteriovenous anastomosis for the treatment of uncontrolled systemic arterial hypertension, exploiting the physical properties of the arterial vasculature.

OBJECTIVES: Uncontrolled hypertension, whether due to drug resistance or poor adherence and persistence, remains a problem in many patients. The ROX coupler is a novel technology designed to reduce arterial blood pressure consequent to the predicted physical effects of reducing vascular resistance and improving arterial compliance. This article describes the technical aspects of the device and implantation procedure, results from a preclinical study, patient selection criteria, and potential complications of this therapy for uncontrolled hypertension. BACKGROUND: The coupler is a self-expanding, stent-like device that exploits the mechanical effects of the creation of a low-resistance, high-compliance venous segment to the central arterial tree, and can be implanted in a standard catheterization laboratory under fluoroscopic guidance. METHODS: Preclinical studies were conducted in sheep with acute or chronic hypertension. The devices were implanted in the aorta for up to 12 months. The anastomoses were evaluated for patency, healing, conformation into the artery and vein, and complications. RESULTS: Deployment of the anastomotic device in ovine aortas for up to 12 months showed optimal anastomotic patency in all animals with proper healing and conformation of the device into the artery and the vein. There was no significant residual mural thrombus and minimal to moderate intimal thickening at the vein outflow, consistent with expected arterialization. CONCLUSIONS: A novel arteriovenous coupler for percutaneous placement in the iliac vasculature is under clinical investigation as a potential treatment modality for selected patients with uncontrolled hypertension. Initial results from patients with uncontrolled hypertension are expected in Autumn 2014.

Central iliac arteriovenous anastomosis for hypertension: targeting mechanical aspects of the circulation.

Raised blood pressure is the leading attributable risk factor for global morbidity and mortality. Real world data demonstrates that half of treated patients are at elevated cardiovascular risk because of inadequately controlled BP. In addition to pharmacotherapy, certain interventional strategies to reduce blood pressure and cardiovascular risk in hypertension can be considered according to international guidelines. One of the newer technologies entering this field is a proprietary arteriovenous coupler device that forms a fixed flow arteriovenous conduit in the central vasculature. In this review, we examine the development of and rationale for the creation of a central arteriovenous anastomosis in patients with hypertension and review the proposed mechanisms by which it may ameliorate hypertension. We critically review the clinical trial evidence base to date and postulate on future therapeutic directions.

Ambulatory blood pressure changes after renal sympathetic denervation in patients with resistant hypertension.

BACKGROUND: Catheter-based renal sympathetic denervation (RDN) reduces office blood pressure (BP) in patients with resistant hypertension according to office BP. Less is known about the effect of RDN on 24-hour BP measured by ambulatory BP monitoring and correlates of response in individuals with true or pseudoresistant hypertension. METHODS AND RESULTS: A total of 346 uncontrolled hypertensive patients, separated according to daytime ambulatory BP monitoring into 303 with true resistant (office systolic BP [SBP] 172.2±22 mm Hg; 24-hour SBP 154±16.2 mm Hg) and 43 with pseudoresistant hypertension (office SBP 161.2±20.3 mm Hg; 24-hour SBP 121.1±19.6 mm Hg), from 10 centers were studied. At 3, 6, and 12 months follow-up, office SBP was reduced by 21.5/23.7/27.3 mm Hg, office diastolic BP by 8.9/9.5/11.7 mm Hg, and pulse pressure by 13.4/14.2/14.9 mm Hg (n=245/236/90; P for all <0.001), respectively. In patients with true treatment resistance there was a significant reduction with RDN in 24-hour SBP (-10.1/-10.2/-11.7 mm Hg, P<0.001), diastolic BP (-4.8/-4.9/-7.4 mm Hg, P<0.001), maximum SBP (-11.7/-10.0/-6.1 mm Hg, P<0.001) and minimum SBP (-6.0/-9.4/-13.1 mm Hg, P<0.001) at 3, 6, and 12 months, respectively. There was no effect on ambulatory BP monitoring in pseudoresistant patients, whereas office BP was reduced to a similar extent. RDN was equally effective in reducing BP in different subgroups of patients. Office SBP at baseline was the only independent correlate of BP response. CONCLUSIONS: RDN reduced office BP and improved relevant aspects of ambulatory BP monitoring, commonly linked to high cardiovascular risk, in patients with true-treatment resistant hypertension, whereas it only affected office BP in pseudoresistant hypertension.

Dissociation between blood pressure and heart rate response to hypoxia after bilateral carotid body removal in men with systolic heart failure.

While the ventilatory response to hypoxia is known to be mediated by the carotid bodies, the origin of the haemodynamic alterations evoked by hypoxia is less certain. Bilateral carotid body removal (CBR) performed to treat congestive heart failure may serve as a model to improve our understanding of haemodynamic responses to hypoxia in humans. We studied six congestive heart failure patients before and 1 month after CBR [median (interquartile range): age, 58.5 (56-61) years old; and ejection fraction, 32 (25-34)%]. Peripheral chemosensitivity (hypoxic ventilatory response) was equated to the slope relating lowest oxygen saturation to highest minute ventilation following exposures to hypoxia. Likewise, systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR) slopes were calculated as slopes relating the lowest oxygen saturations to the highest SBP, DBP and HR responses. We found that CBR reduces the hypoxic ventilatory response (91%, P < 0.05), SBP (71%, P < 0.05) and DBP slopes (59%, P = 0.07). In contrast, the HR slope remained unchanged. The dissociation between the blood pressure and HR responses after CBR shows involvement of a different chemoreceptive site(s) maintaining the response to acute hypoxia. We conclude that carotid bodies are responsible for ventilatory and blood pressure responses, while the HR response might be mediated by the aortic bodies. The significant reduction of the blood pressure response to hypoxia after CBR suggests a decrease in sympathetic tone, which is of particular clinical relevance in congestive heart failure.

The thrill of success: central arterial-venous anastomosis for hypertension.

Excess blood pressure remains the most important risk factor for cardiovascular and renal disease. Poly pharmacy has been proved safe and effective under clinical trial circumstances; however, the majority of patients fail to sustain pharmaceutical persistence and adherence. The opportunity to offer patients a treatment or device in addition or perhaps instead of drug therapy alone may significantly broaden the options for patients and allow greater success in hypertensive therapy. In this review, we examine the potential of a fixed-volume central arterial-venous anastomosis to reduce blood pressure in hypertensive patients, review possible mechanisms by which the anastomosis may reduce blood pressure, and consider the unique clinical trial opportunities posed by this therapy.

Efficacy and safety of sympathetic mapping and ablation of renal nerves for the treatment of hypertension (SMART): 6-month follow-up of a randomised, controlled trial.

Background: Previous trials of renal denervation (RDN) have been designed to investigate reduction of blood pressure (BP) as the primary efficacy endpoint using non-selective RDN without intraoperatively verified RDN success. It is an unmet clinical need to map renal nerves, selectively denervate renal sympathetic nerves, provide readouts for the interventionalists and avoid futile RDN. We aimed to examine the safety and efficacy of renal nerve mapping/selective renal denervation (msRDN) in patients with uncontrolled hypertension (HTN) and determine whether antihypertensive drug burden is reduced while office systolic BP (OSBP) is controlled to target level (＜140 mmHg). Methods: We conducted a randomized, prospective, multicenter, single-blinded, sham-controlled trial. The study combined two efficacy endpoints at 6 months as primary outcomes: The control rate of patients with OSBP ＜140 mmHg (non-inferior outcome) and change in the composite index of antihypertensive drugs (Drug Index) in the treatment versus Sham group (superior outcome). This design avoids confounding from excess drug-taking in the Sham group. Antihypertensive drug burden was assessed by a composite index constructed as: Class N (number of classes of antihypertensive drugs) × (sum of doses). 15 hospitals in China participated in the study and 220 patients were enrolled in a 1:1 ratio (msRDN vs Sham). The key inclusion criteria included: age (18-65 years old), history of essential HTN (at least 6 months), heart rate (≥70 bpm), OSBP (≥150 mmHg and ≤180 mmHg), ambulatory BP monitoring (ABPM, 24-h SBP ≥130 mmHg or daytime SBP ≥135 mmHg or nighttime SBP ≥120 mmHg), renal artery stenosis (＜50%) and renal function (eGFR ＞45 mL/min/1.73 m2). The catheter with both stimulation and ablation functions was inserted in the distal renal main artery. The RDN site (hot spot) was selected if SBP increased (≥5 mmHg) by intra-renal artery (RA) electrical stimulation; an adequate RDN was confirmed by repeated electronic stimulation if no increase in BP otherwise, a 2nd ablation was performed at the same site. At sites where there was decreased SBP (≥5 mmHg, cold spot) or no BP response (neutral spot) to stimulation, no ablation was performed. The mapping, ablation and confirmation procedure was repeated until the entire renal main artery had been tested then either treated or avoided. After msRDN, patients had to follow a predefined, vigorous drug titration regimen in order to achieve target OSBP (＜140 mmHg). Drug adherence was monitored by liquid chromatography-tandem mass spectrometry analysis using urine. This study is registered with ClinicalTrials.gov (NCT02761811) and 5-year follow-up is ongoing. Findings: Between July 8, 2016 and February 23, 2022, 611 patients were consented, 220 patients were enrolled in the study who received standardized antihypertensive drug treatments (at least two drugs) for at least 28 days, presented OSBP ≥150 mmHg and ≤180 mmHg and met all inclusion and exclusion criteria. In left RA and right RA, mapped sites were 8.2 (3.0) and 8.0 (2.7), hot/ablated sites were 3.7 (1.4) and 4.0 (1.6), cold spots were 2.4 (2.6) and 2.0 (2.2), neutral spots were 2.0 (2.1) and 2.0 (2.1), respectively. Hot, cold and neutral spots was 48.0%, 27.5% and 24.4% of total mapped sites, respectively. At 6 M, the Control Rate of OSBP was comparable between msRDN and Sham group (95.4% vs 92.8%, p = 0.429), achieved non-inferiority margin -10% (2.69%; 95% CI -4.11%, 9.83%, p ＜ 0.001 for non-inferiority); the change in Drug Index was significantly lower in msRDN group compared to Sham group (4.37 (6.65) vs 7.61 (10.31), p = 0.010) and superior to Sham group (-3.25; 95% CI -5.56, -0.94, p = 0.003), indicating msRDN patients need significantly fewer drugs to control OSBP ＜140 mmHg. 24-hour ambulatory SBP decreased from 146.8 (13.9) mmHg by 10.8 (14.1) mmHg, and from 149.8 (12.8) mmHg by 10.0 (14.0) mmHg in msRDN and Sham groups, respectively (p < 0.001 from Baseline; p > 0.05 between groups). Safety profiles were comparable between msRDN and Sham groups, demonstrating the safety and efficacy of renal mapping/selective RDN to treat uncontrolled HTN. Interpretation: The msRDN therapy achieved the goals of reducing the drug burden of HTN patients and controlling OSBP <140 mmHg, with only approximately four targeted ablations per renal main artery, much lower than in previous trials. Funding: SyMap Medical (Suzhou), LTD, Suzhou, China.

Renal sympathetic denervation for treatment of drug-resistant hypertension: one-year results from the Symplicity HTN-2 randomized, controlled trial.

BACKGROUND: Renal sympathetic nerve activation contributes to the pathogenesis of hypertension. Symplicity HTN-2, a multicenter, randomized trial, demonstrated that catheter-based renal denervation produced significant blood pressure lowering in treatment-resistant patients at 6 months after the procedure compared with control, medication-only patients. Longer-term follow-up, including 6-month crossover results, is now presented. METHODS AND RESULTS: Eligible patients were on ≥3 antihypertensive drugs and had a baseline systolic blood pressure ≥160 mm Hg (≥150 mm Hg for type 2 diabetics). After the 6-month primary end point was met, renal denervation in control patients was permitted. One-year results on patients randomized to immediate renal denervation (n=47) and 6-month postprocedure results for crossover patients are presented. At 12 months after the procedure, the mean fall in office systolic blood pressure in the initial renal denervation group (-28.1 mm Hg; 95% confidence interval, -35.4 to -20.7; P<0.001) was similar to the 6-month fall (-31.7 mm Hg; 95% confidence interval, -38.3 to -25.0; P=0.16 versus 6-month change). The mean systolic blood pressure of the crossover group 6 months after the procedure was significantly lowered (from 190.0±19.6 to 166.3±24.7 mm Hg; change, -23.7±27.5; P<0.001). In the crossover group, there was 1 renal artery dissection during guide catheter insertion, before denervation, corrected by renal artery stenting, and 1 hypotensive episode, which resolved with medication adjustment. CONCLUSIONS: Control patients who crossed over to renal denervation with the Symplicity system had a significant drop in blood pressure similar to that observed in patients receiving immediate denervation. Renal denervation provides safe and sustained reduction of blood pressure to 1 year.

Clinical predictors and hemodynamic consequences of elevated peripheral chemosensitivity in optimally treated men with chronic systolic heart failure.

AIMS: Augmented peripheral chemoreflex response is an important mechanism in the pathophysiology of chronic heart failure (CHF). This study characterizes prevalence and clinical predictors of this phenomenon in optimally managed male CHF patients, and seeks to describe the hemodynamic consequences of chemoreceptor hypersensitivity. METHODS AND RESULTS: Thirty-four optimally managed CHF patients and 16 control subjects were prospectively studied. Hypoxic ventilatory response (HVR)-a measure of peripheral chemosensitivity-was calculated with the use of short nitrogen gas administrations. Systolic blood pressure (SBP) and heart rate (HR) following transient hypoxic challenges were recorded with a Nexfin monitor. Hemodynamic responses to hypoxia were expressed by the linear slopes between oxygen saturation (%) and SBP (mm Hg) or HR (beats/min). Elevated HVR was present in 15 (44%) of the CHF patients. Patients with elevated HVR exhibited higher levels of N-terminal pro-B-type natriuretic peptide, lower left ventricular ejection fraction, and higher prevalence of atrial fibrillation. CHF patients with elevated HVR had significantly greater SBP and HR responses to hypoxia than CHF patients with normal HVR. CONCLUSIONS: Despite comprehensive pharmacotherapy, elevated HVR is prevalent in CHF patients, related to severity of the disease and associated with augmented hemodynamic responses to hypoxia. CHF patients with elevated HVR may be prone to unfavorable hemodynamic changes.

Revelations about carotid body function through its pathological role in resistant hypertension.

Much recent attention has been given to the carotid body because of its potential role in cardiovascular disease states. One disease, neurogenic hypertension, characterised by excessive sympathetic activity, appears dependent on carotid body activity that may or may not be accompanied by sleep-disordered breathing. Herein, we review recent literature suggesting that the carotid body acquires tonicity in hypertension. We predict that carotid glomectomy will be a powerful way to temper excessive sympathetic discharge in diseases such as hypertension. We propose a model to explain that signalling from the 'hypertensive' carotid body is tonic, and hypothesise that there will be a sub-population of glomus cells that channel separately into reflex pathways controlling sympathetic motor outflows.