Renal artery denervation has re-emerged as a potential therapeutic option for patients with hypertension, especially those resistant to conventional pharmacotherapy. This comprehensive review explores the importance of careful patient selection, procedural techniques, clinical efficacy, safety considerations, and future directions of renal artery denervation in hypertension management. Drawing upon a wide range of available evidence, this review aims to provide a thorough understanding of the procedure and its role in contemporary hypertension treatment paradigms.

Objective: Acute coronary syndromes (ACS) are common, but their incidence and outcome might depend greatly on how data are collected. We compared case ascertainment rates for ACS and myocardial infarction (MI) in a single institution using several different strategies.Methods: The Hull and East Yorkshire Hospitals serve a population of similar to 560 000. Patients admitted with ACS to cardiology or general medical wards were identified prospectively by trained nurses during 2005. Patients with a death or discharge code of MI were also identified by the hospital information department and, independently, from Myocardial Infarction National Audit Project (MINAP) records. The hospital laboratory identified all patients with an elevated serum troponin-T (TnT) by contemporary criteria (>0.03 mu g/L in 2005).Results: The prospective survey identified 1731 admissions (1439 patients) with ACS, including 764 admissions (704 patients) with MIs. The hospital information department reported only 552 admissions (544 patients) with MI and only 206 admissions (203 patients) were reported to the MINAP. Using all 3 strategies, 934 admissions (873 patients) for MI were identified, for which TnT was >1 mu g/L in 443, 0.04-1.0 mu g/L in 435, <= 0.03 mu g/L in 19 and not recorded in 37. A further 823 patients had TnT >0.03 mu g/L, but did not have ACS ascertained by any survey method. Of the 873 patients with MI, 146 (16.7%) died during admission and 218 (25.0%) by 1 year, but ranging from 9% for patients enrolled in the MINAP to 27% for those identified by the hospital information department.Conclusions: MINAP and hospital statistics grossly underestimated the incidence of MI managed by our hospital. The 1-year mortality was highly dependent on the method of ascertainment.

Objectives In the presence of a chronically occluded coronary artery, the collateral circulation matures by a process of arteriogenesis; however, there is considerable variation between individuals in the functional capacity of that collateral network. This could be explained by differences in endothelial health and function. We aimed to examine the relationship between the functional extent of collateralization and levels of biomarkers that have been shown to relate to endothelial health. Methods We measured four potential biomarkers of endothelial health in 34 patients with mature collateral networks who underwent a successful percutaneous coronary intervention (PCI) for a chronic total coronary occlusion (CTO) before PCI and 6–8 weeks after PCI, and examined the relationship of biomarker levels with physiological measures of collateralization. Results We did not find a significant change in the systemic levels of sICAM-1, sE-selectin, microparticles or tissue factor 6–8 weeks after PCI. We did find an association between estimated retrograde collateral flow before CTO recanalization and lower levels of sICAM-1 (r=0.39, P=0.026), sE-selectin (r=0.48, P=0.005) and microparticles (r=0.38, P=0.03). Conclusion Recanalization of a CTO and resultant regression of a mature collateral circulation do not alter systemic levels of sICAM-1, sE-selectin, microparticles or tissue factor. The identified relationship of retrograde collateral flow with sICAM-1, sE-selectin and microparticles is likely to represent an association with an ability to develop collaterals rather than their presence and extent.

Background Renal denervation (RDN) may lower blood pressure (BP); however, it is unclear whether medication changes may be confounding results. Furthermore, limited data exist on pattern of ambulatory blood pressure (ABP) response—particularly in those prescribed aldosterone antagonists at the time of RDN. Methods We examined all patients treated with RDN for treatment-resistant hypertension in 18 UK centres. Results Results from 253 patients treated with five technologies are shown. Pre-procedural mean office BP (OBP) was 185/102 mmHg (SD 26/19; n = 253) and mean daytime ABP was 170/98 mmHg (SD 22/16; n = 186). Median number of antihypertensive drugs was 5.0: 96 % ACEi/ARB; 86 % thiazide/loop diuretic and 55 % aldosterone antagonist. OBP, available in 90 % at 11 months follow-up, was 163/93 mmHg (reduction of 22/9 mmHg). ABP, available in 70 % at 8.5 months follow-up, was 158/91 mmHg (fall of 12/7 mmHg). Mean drug changes post RDN were: 0.36 drugs added, 0.91 withdrawn. Dose changes appeared neutral. Quartile analysis by starting ABP showed mean reductions in systolic ABP after RDN of: 0.4; 6.5; 14.5 and 22.1 mmHg, respectively ( p < 0.001 for trend). Use of aldosterone antagonist did not predict response ( p > 0.2). Conclusion In 253 patients treated with RDN, office BP fell by 22/9 mmHg. Ambulatory BP fell by 12/7 mmHg, though little response was seen in the lowermost quartile of starting blood pressure. Fall in BP was not explained by medication changes and aldosterone antagonist use did not affect response.

ObjectivesThe aim of this study was to compare microvascular resistance under both baseline and hyperemic conditions immediately after percutaneous coronary intervention (PCI) of a chronic total occlusion (CTO) with an unobstructed reference vessel in the same patientBackgroundMicrovascular dysfunction has been reported to be prevalent immediately after CTO PCI. However, previous studies have not made comparison with a reference vessel. Patients with a CTO may have global microvascular and/or endothelial dysfunction, making comparison with established normal values misleading.MethodsAfter successful CTO PCI in 21 consecutive patients, coronary pressure and flow velocity were measured at baseline and hyperemia in distal segments of the CTO/target vessel and an unobstructed reference vessel. Hemodynamics including hyperemic microvascular resistance (HMR), basal microvascular resistance (BMR), and instantaneous minimal microvascular resistance at baseline and hyperemia were calculated and compared between reference and target/CTO vessels.ResultsAfter CTO PCI, BMR was reduced in the target/CTO vessel compared with the reference vessel: 3.58 mm Hg/cm/s vs 4.94 mm Hg/cm/s, difference −1.36 mm Hg/cm/s (−2.33 to −0.39, p = 0.008). We did not detect a difference in HMR: 1.82 mm Hg/cm/s vs 2.01 mm Hg/cm/s, difference −0.20 (−0.78 to 0.39, p = 0.49). Instantaneous minimal microvascular resistance correlated strongly with the length of stented segment at baseline (r = 0.63, p = 0.005) and hyperemia (r = 0.68, p = 0.002).ConclusionsBMR is reduced in a recanalized CTO in the immediate aftermath of PCI compared to an unobstructed reference vessel; however, HMR appears to be preserved. A longer stented segment is associated with increased microvascular resistance. © 2016 Wiley Periodicals, Inc.

Objective: To describe the UK experience with Renal Denervation (RDN). Design and method: RDN may lower blood pressure (BP) in people with resistant hypertension. The UK Renal Denervation Affiliation is an independent, investigator-led initiative. Each centre had done >5 cases. A standardised dataset was collected retrospectively, anonymised and submitted to the coordinating centre for analysis. Results: Results from 246 cases from 16 centres are reported. Average cases per centre was 15. Five different ablation technologies were used: unipolar catheters in 198 and multipolar in 48. Mean age was 56.7 years, 53% female, 87% Caucasian and 27% diabetes. Previous stroke/TIA - 24%; myocardial infarction - 15%; proteinuria - 26%. Patients were screened by a mean of 1.6 specialists with an interest in hypertension. 86% attended specialist hypertension clinics. On average 4.7 drugs were used before RDN; 95% were on 3+ drugs; 90% were on RAS blockers, 90% diuretics and 56% aldosterone antagonists at time of RDN. Pre-RDN mean office BP was 186/102 mmHg. Ambulatory blood pressure monitoring (ABP) data were available for 179 patients (73%). Average pre-RDN ABP was: daytime - 170/98; night - 154/86. Average follow-up was 10.7 months. Mean Office BP post-RDN was 164/93, a fall of 22/9 mmHg (P < 0.001). In 24%, office SBP fell 40+ mmHg. On average, 0.8 drugs were withdrawn per patient and 0.3 drugs added between RDN and follow-up. Mean daytime ABP after RDN was 158/92 and nighttime ABP 145/81 - fall in daytime ABP was 12/6 (p < 0.001). 18% had a drop in day systolic ABP of >20 mmHg. A decrease in GFR >25% was seen at 10 months in 5% patients. Otherwise, no significant complications were seen. Conclusions: In a cohort of 246 patients from 16 UK centres who had undergone renal denervation, a significant fall in blood pressure was observed. Office BP fell by 22/9 mmHg. Daytime ambulatory BP fell by 12/6 mmHg. Carefully selected patients with resistant hypertension exhibited significant BP reduction following RDN. This was a group with severe hypertension who had been well characterised in specialist hypertension clinics. Drug additions/withdrawals did not appear to explain the BP fall.

Introduction An association between improved survival and successful PCI of chronic total coronary occlusions (CTO) when compared with failed PCI has been widely reported. However a comparison between elective medical therapy and CTO PCI is more relevant to clinical decision making. We compared long-term clinical outcomes in a cohort of patients with an identified CTO on angiography between these two treatment groups, hypothesising there would be a difference in all-cause mortality at 5 year follow-up. Methods Patients found to have a CTO on angiography between 2002 and 2008, without prior CABG or important structural heart disease in a single tertiary centre were identified using a dedicated database. Patients undergoing CTO PCI and elective medical therapy to the CTO were matched using a propensity score to adjust for baseline clinical and angiographic differences. Events at follow-up were identified using national death certification records and national registries for myocardial infarction, CABG and PCI. Results In total 1957 patients were identified, a CTO was treated by PCI in 405 (20.7%) and medical therapy in 667 (34.1%), 885 (45.2%) patients underwent CABG. Of those treated by PCI or medical therapy, propensity score matching identified 389 pairs of patients. PCI was successful in 238 patients (61.2%). There was no difference in the primary study objective of 5 year mortality between the propensity matched treatment groups (CTO PCI: 10.8%, medical therapy: 15.7%; HR 0.74; 95% CI 0.49 to 1.11; p = 0.146), or after adjustment for Syntax score: (HR 0.81; 95% CI 0.53–1.25; p = 0.336). There remained no difference if only the 238 matched pairs in which CTO PCI was successful were included (HR 0.83; 95% CI 0.48 to 1.42; p = 0.493). There was an increase in repeat revascularisation associated with CTO PCI (HR 2.18; 95% CI 1.49–3.18; p < 0.001). This difference was not present in the successful PCI matched pair subgroup (HR 0.79; 95% CI 0.45–1.37; p = 0.397). Conclusions Using an alternative approach to much of the existing literature, we have not demonstrated an associated difference in survival between patients with a CTO treated by PCI versus those in whom the CTO was treated medically. Doubt remains as to whether PCI of a CTO should be performed on grounds of prognosis.

Background— The presence of a concomitant chronic total coronary occlusion (CTO) and a large collateral contribution might alter the fractional flow reserve (FFR) of an interrogated vessel, rendering the FFR unreliable at predicting ischemia should the CTO vessel be revascularized and potentially affecting the decision on optimal revascularization strategy. We tested the hypothesis that donor vessel FFR would significantly change after percutaneous coronary intervention of a concomitant CTO. Methods and Results— In consecutive patients undergoing percutaneous coronary intervention of a CTO, coronary pressure and flow velocity were measured at baseline and hyperemia in proximal and distal segments of both nontarget vessels, before and after percutaneous coronary intervention. Hemodynamics including FFR, absolute coronary flow, and the coronary flow velocity–pressure gradient relation were calculated. After successful percutaneous coronary intervention in 34 of 46 patients, FFR in the predominant donor vessel increased from 0.782 to 0.810 (difference, 0.028 [0.012 to 0.044]; P =0.001). Mean decrease in baseline donor vessel absolute flow adjusted for rate pressure product: 177.5 to 139.9 mL/min (difference −37.6 [−62.6 to −12.6]; P =0.005), mean decrease in hyperemic flow: 306.5 to 272.9 mL/min (difference, −33.5 [−58.7 to −8.3]; P =0.011). Change in predominant donor vessel FFR correlated with angiographic (%) diameter stenosis severity ( r =0.44; P =0.009) and was strongly related to stenosis severity measured by the coronary flow velocity–pressure gradient relation ( r =0.69; P <0.001). Conclusions— Recanalization of a CTO results in a modest increase in the FFR of the predominant collateral donor vessel associated with a reduction in coronary flow. A larger increase in FFR is associated with greater coronary stenosis severity.

Objective There is little published data reporting outcomes for those found to have a chronic total coronary occlusion (CTO) that is electively treated medically versus those treated by percutaneous coronary intervention (PCI). We sought to compare long-term clinical outcomes between patients treated by PCI and elective medical therapy in a consecutive cohort of patients with an identified CTO.Methods Patients found to have a CTO on angiography between January 2002 and December 2007 in a single tertiary centre were identified using a dedicated database. Those undergoing CTO PCI and elective medical therapy to the CTO were propensity matched to adjust for baseline clinical and angiographic differences.Results In total, 1957 patients were identified, a CTO was treated by PCI in 405 (20.7%) and medical therapy in 667 (34.1%), 885 (45.2%) patients underwent coronary artery bypass graft surgery. Of those treated by PCI or medical therapy, propensity score matching identified 294 pairs of patients, PCI was successful in 177 patients (60.2%). All-cause mortality at 5 years was 11.6% for CTO PCI and 16.7% for medical therapy HR 0.63 (0.40 to 1.00, p=0.052). The composite of 5-year death or myocardial infarction occurred in 13.9% of the CTO PCI group and 19.6% in the medical therapy group, HR 0.64 (0.42 to 0.99, p=0.043). Among the CTO PCI group, if the CTO was revascularised by any means during the study period, 5-year mortality was 10.6% compared with 18.3% in those not revascularised in the medical therapy group, HR 0.50 (0.28-0.88, p=0.016).Conclusions Revascularisation, but not necessarily PCI of a CTO, is associated with improved long-term survival relative to medical therapy alone.

Introduction Fractional flow reserve (FFR) guided angioplasty has been shown to have a beneficial effect on clinical outcome in patients with multi-vessel coronary disease. However, multi-vessel disease is frequently accompanied by a chronic total occlusion (CTO). We have limited understanding of the effect of the donation of a collateral supply to collateral dependent myocardium on the FFR. Marked changes in non-target vessel FFR post recanalisation of CTOs have been reported, but the consistency of this phenomenon remains uncertain and changes in haemodynamic indices immediately post-angioplasty might be confounded by the effect of the vessel trauma of angioplasty on the microvasculature. If the phenomenon is consistent, we might expect haemodynamics in a vessel donating collaterals to a CTO to be dependent on the extent of angiographic collateral flow originating from it. Methods Prior to CTO angioplasty in 22 patients, simultaneous pressure and flow were measured at rest and during hyperaemia in the distal and proximal segment of each non-target vessel. Absolute coronary flow, coronary flow reserve, hyperaemic microvascular resistance and fractional flow reserve were calculated. Blinded to haemodynamic measurements, the major collateral donor vessel was selected and each vessel was graded by the size of the largest collateral branch which originated from it by collateral connexion (CC) grade (0 = no continuous connexion, 1 = threadlike connexion, 2 = side branch like connexion). Haemodynamic measurements were compared between the major and minor collateral donor vessels using a paired t-test. Results All patients had right dominant coronary anatomy. The target vessel was the left anterior descending artery (LAD) in 9 patients, circumflex artery (LCx) in 2 and right coronary artery (RCA) in 11. All target vessels were filled by a modified Rentrop grade of >2 (2 n = 12, 3 n = 10). Angiographic characteristics are listed in Table 1 and haemodynamic measurements are listed in Table 2. In spite of clearly increased angiographic collateral donation, we did not identify any associated significant difference between haemodynamic indices. Abstract 72 Table 1 Minor Collateral Donorn Major Collateral Donorn CC class (0,1,2) 2 3 11 1 8 11 0 11 0 Vessel LAD 7 6 LCx 15 5 RCA 0 11 Abstract 72 Table 2 Minor Collateral Donor Mean(SD) Major Collateral Donor Mean(SD) Difference (95% CI, p-value) Donor Vessel Duke Jeopardy Score 3.27(1.91) 4.09(1.44) 0.75 (-0.61-2.11, p =. 27) Maximum diameter stenosis (%) 36.9(13.6) 32.6(14.9) -4.3 (-11.5-3.0, p =. 23) Fractional Flow Reserve 0.82(0.11) 0.80(0.10) -0.02 (-0.07-0.04, p =. 55) Hyperaemic Microvascular Resistance (mmHg/cm/s) 2.19(0.87) 2.01(0.95) -0.18 (-0.74-0.38, p =. 51) Coronary Flow Reserve 2.11(0.61) 2.13(0.78) -0.03 (-0.36-0.42, p =. 88) Hyperaemic Absolute Flow (ml/min) 168.8(97.7) 189.4(126.9) 20.6 (-30.7-72.0,p =. 41) Crude Resting Absolute Flow (ml/min) 79.5(43.0) 86.0(37.1) 6.4 (-13.6-26.5,p =. 51) Resting Absolute Flow adjustedfor Rate Pressure Product (ml/min) 105.8(61.3) 111.6(58.7) 5.8 (-21.0-32.6, p =. 66) Conclusion The mechanism for a large rise in non-target vessel FFR post CTO angioplasty must involve one or more of a fall in absolute flow, a fall in coronary flow reserve or an increase in microvascular resistance. One would expect that change to move towards the norm for a vessel donating fewer collateral branches. The absence of a difference in any of these haemodynamic indices between paired non-target vessels with differing CC grades (and therefore different extents of collateral ‘donation’) would suggest thatthe large changes in FFR which have been reported might only represent a publication biassed measurement extreme, rather than the rule.

Introduction: Although an association between improved survival and successful PCI of chronic total coronary occlusions (CTO) compared with failed PCI has been widely reported, there is little published data reporting outcomes for those found to have a CTO which is electively treated medically versus those treated by PCI; a comparison which is more pertinent to clinical decision making. Our aim was to compare long-term clinical outcomes in a cohort of patients with an identified CTO on angiography between these two treatment groups. We hypothesised there would be a significant difference in all-cause mortality at 5 year follow-up. Methods: Patients found to have a CTO on angiography between 2002 and 2008, without prior CABG or important structural heart disease in a single tertiary centre were identified using a dedicated database. Patients undergoing CTO PCI and elective medical therapy to the CTO were propensity matched to adjust for baseline clinical and angiographic differences. Events at follow-up were identified using national death certification records and national registries for myocardial infarction, CABG and PCI. Comparisons were stratified by matched pair. Results: In total 1957 patients were identified, a CTO was treated by PCI in 405(20.7%) and medical therapy in 667(34.1%), 885(45.2%) patients underwent CABG. Of those treated by PCI or medical therapy, propensity score matching identified 389 pairs of patients. PCI was successful in 238 patients (61.2%). There was no difference in the primary study objective of 5 year mortality between the propensity matched treatment groups (CTO PCI: 10.8%, medical therapy: 15.7%; HR 0.74; 95% CI 0.49 to 1.11; p=0.146). There remained no difference if only the 238 matched pairs in which CTO PCI was successful were included (HR 0.83; 95% CI 0.48 to 1.42; p=0.493). There was an increase in repeat revascularization associated with CTO PCI (HR 2.18; 95% CI 1.49-3.18; p<0.001). This difference was not present in the successful PCI matched pair subgroup (HR 0.79; 95% CI 0.45-1.37; p=0.397). Conclusions: Using an alternative approach to much of the existing literature, we did not demonstrate an associated difference in survival between patients with a CTO treated by PCI versus those in whom the CTO was treated medically.

Resistant hypertension (RHTN) is defined as the failure to achieve goal blood pressure (BP), despite adherence to maximally tolerated doses of an appropriate regimen of 3 antihypertensive agents, including a diuretic.1,2 Interest surrounding its evaluation, diagnosis, and treatment has gained significant momentum for the following several reasons: (1) the recognition that patients with true RHTN appear to lie at the extreme end of an already high-risk cardiovascular (CV) morbidity and mortality continuum3–5; (2) the acceptance that accurate estimates of the incidence and prevalence of RHTN remain largely unknown5–8; (3) the need to establish robust prognostic associations to benchmark the degree of benefit gained from timely and consistent management; (4) the need to define the optimal pharmacotherapeutic regimen for RHTN; (5) evidence that RHTN may, at least in part, be mediated by chronic activation of the sympathetic nervous system (SNS)9; and (6) the subsequent emergence of percutaneous sympathetic denervation of the renal arteries—a novel intervention that could stimulate a paradigm shift in the way we manage not only treatment-resistant systemic HTN, but also a myriad of pathophysiological entities associated with chronically augmented SNS activation.10In this review we focus on the evolution of renal sympathetic denervation (RSDN) therapy; its role in the management of RHTN; current trial data; the wider application of renal denervation in the treatment of heart failure (HF), arrhythmia, and the metabolic syndrome; and emerging technologies for this potential device-based standard of care.The renal SNS comprises a dense network of postganglionic efferent fibers that run from the hypothalamus to the kidney via pre- and paravertebral sympathetic ganglia (T10–L2).11,12 Afferent renal sympathetic nerves emerge predominantly from the renal pelvic wall, where mechanoreceptors respond to stretch and chemoreceptors detect renal ischemia and alterations of the biochemical …

Aortic atherosclerosis reduces compliance in the systemic circulation and increases peripheral resistance, afterload and left ventricular wall stress. In patients with heart failure, these changes can impair left ventricular systolic function and energy efficiency, which could reduce exercise capacity. Though the interaction and the impact of aortic atherosclerosis on left ventricular function have been investigated, its prognostic implications in patients with heart failure are unclear. We used cardiac magnetic resonance imaging and gadolinium-enhanced abdominal aortography to investigate the prevalence and prognostic impact of atherosclerotic disease of the abdominal aorta and its side branches in 355 patients with heart failure. Sclerotic abdominal aortic disease was defined as a luminal narrowing >50% of the aorta and its side branches or the presence of abdominal aortic aneurysm. Patients with disease of the aorta and its branches were older (P < 0.0001), had overall longer stay in hospital (P = 0.006) and had more admissions (P = 0.001) and worse prognosis (hazard ratio: 1.97, 95% confidence interval: 1.29–3.00, P = 0.002) than those without. In a multivariable model, increasing age and pulse pressure, diabetes mellitus and increasing left ventricular end-diastolic volume were associated with a worse prognosis, but sclerotic abdominal aortic disease was not independently related to outcome (hazard ratio: 1.06; 95% confidence interval: 0.64–1.74; P = 0.823). These data demonstrate that atherosclerosis of the abdominal aorta and its side branches is common and associated with increased morbidity in patients with chronic heart failure. How such disease should be managed remains uncertain, but its recognition and characterisation are the first steps in finding out.