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Sustained blood pressure reductions after radiofrequency (RF) renal denervation (RDN) have been reported to 3 years in patients with uncontrolled hypertension. However, mechanistic data to support procedural durability are lacking. We aimed to quantify the long-term nerve anatomic and functional effects of RF RDN in a preclinical model.Bilateral RF RDN was performed in 20 normotensive swine. Renal tissue samples were obtained in the RDN-treated groups at 7 ( n = 6), 28 ( n = 6), and 180 days ( n = 8) postprocedure for quantification of cortical norepinephrine (NE) levels and renal cortical axon density. Tissue fibrosis, necrosis and downstream nerve fiber atrophy (axonal loss) were also scored for each sample. Three additional untreated groups ( n = 6, n = 6 and n = 8, respectively) served as control.Pathologic nerve changes were characterized by necrosis in the ablated region at 7 days that partially resolved by 28 days and fully resolved at 180 days. Axonal loss was apparent within and downstream to the ablation regions and was evident at 7, 28 and 180 days in the main vessel and branch vessels. Consequently, renal cortical axon density and corresponding cortical NE levels were significantly reduced at 7 days in the RDN vs. control group and remained suppressed at 180 days.Reductions in renal NE, cortical axon density and downstream axonal loss caused by axonal destruction persisted through 180 days post-RDN in a normotensive swine model. These results suggest functional nerve regrowth after RF RDN is unlikely and support published clinical evidence that the procedure results in durable blood pressure reduction.

Background Ischemia-reperfusion injury remains a major clinical problem in patients with ST-elevation myocardial infarction (STEMI), leading to myocardial damage despite early reperfusion by primary percutaneous coronary intervention (PPCI). There are no effective therapies to limit ischemia-reperfusion injury, which is caused by multiple pathways activated by rapid tissue reoxygenation and the generation of reactive oxygen species (ROS). FDY-5301 contains sodium iodide, a ubiquitous inorganic halide and elemental reducing agent that can act as a catalytic anti-peroxidant. We tested the feasibility, safety and potential utility of FDY-5301 as a treatment to limit ischemia-reperfusion injury, in patients with first-time STEMI undergoing emergency PPCI. Methods STEMI patients (n = 120, median 62 years) presenting within 12 h of chest pain onset were randomized at 20 PPCI centers, in a double blind Phase 2 clinical trial, to receive FDY-5301 (0.5, 1.0 or 2.0 mg/kg) or placebo prior to reperfusion, to evaluate the feasibility endpoints. Participants underwent continuous ECG monitoring for 14 days after PPCI to address pre-specified cardiac arrhythmia safety end points and cardiac magnetic resonance imaging (MRI) at 72 h and at 3 months to assess exploratory efficacy end points. Results Intravenous FDY-5301 was delivered before re-opening of the infarct-related artery in 97% participants and increased plasma iodide levels ~1000-fold within 2 min. There was no significant increase in the primary safety end point of incidence of cardiac arrhythmias of concern. MRI at 3 months revealed median final infarct sizes in placebo vs. 2.0 mg/kg FDY-5301-treated patients of 14.9% vs. 8.5%, and LV ejection fractions of 53.9% vs. 63.2%, respectively, although the study was not powered to detect statistical significance. In patients receiving FDY-5301, there was a significant reduction in the levels of MPO, MMP2 and NTproBNP after PPCI, but no reduction with placebo. Conclusions Intravenous FDY-5301, delivered immediately prior to PPCI in acute STEMI, is feasible, safe, and shows potential efficacy. A larger trial is justified to test the effects of FDY-5301 on acute ischemia-reperfusion injury and clinical outcomes. Clinical Trial Registration: CT.gov NCT03470441 ; EudraCT 2017-000047-41

International audience; Objective: The RADIANCE-HTN SOLO trial demonstrated a greater reduction in daytime ambulatory SBP at 2 months by endovascular ultrasound renal denervation than sham procedure. We hypothesized that plasma renin and aldosterone concentrations would be associated with the SBP response to renal denervation.Methods: Hypertensive patients were randomized to renal denervation (n ¼ 74) or sham (n ¼ 72) after a 4-week washout of antihypertensive medications. In a 53-patient subset, 2-month and 6-month plasma renin and aldosterone concentration were measured. Dietary sodium was not controlled.Results: Mean age of the 29 treatment and 24 sham patients was 54 years; 62% were men; 17% black. Daytime ambulatory SBP fell in the denervation but not the sham group at 2 months (-7.8 AE 10.7 vs. -0.1 AE 10.1 mmHg; P ¼ 0.048). Baseline plasma renin and aldosterone concentrations were in the low-normal range, did not change significantly at 2 months in either group and did not predict response to renal denervation. At 6 months, after the addition of antihypertensive medications, there was a significant rise in renin in the sham but not the denervation group.Conclusion: Although renal denervation but not sham resulted in a decrease in daytime ambulatory SBP at 2 months, renin and aldosterone concentrations did neither predict the BP response to renal denervation; nor did they fall after denervation. A rise in renin at 6 months in the sham group likely represents confounding from antihypertensive medications. Whether the BP-lowering effect of renal denervation depends on reducing local intrarenal renin release requires further study.

The blood pressure (BP) lowering response to renal denervation (RDN) remains variable with about one-third of patients not responding to ultrasound or radiofrequency RDN. Identification of predictors of the BP response to RDN is needed to optimize patient selection for this therapy. This is a post-hoc analysis of the RADIANCE-HTN SOLO study. BP response to RDN was measured by the change in daytime ambulatory systolic blood pressure (dASBP) at 2 months post procedure. Univariate regression was used initially to assess potential predictors of outcome followed by multivariate regression analysis. In the univariate analysis, predictors of response to RDN were higher baseline daytime ambulatory diastolic blood pressure (dADBP), the use of antihypertensive medications at screening, and presence of orthostatic hypertension (OHTN) whilst the presence of untreated accessory arteries was a negative predictor of response. Multivariate analysis determined that dADBP and use of antihypertensive medications were predictors of response to RDN with a trend for OHTN to predict response. Obese females also appeared to be better responders to RDN in an interaction model. RDN is more effective in patients with elevated baseline dADBP and those with OHTN, suggesting increased peripheral vascular resistance secondary to heightened sympathetic tone. These assessments are easy to perform in clinical setting and may help in phenotyping patients who will respond better to RDN.

Background Left ventricular (LV) hypertrophy (LVH) in uncontrolled hypertension is an independent predictor of mortality, though its regression with treatment improves outcomes. Retrospective data suggest that early control of hypertension provides a prognostic advantage and this strategy is included in the 2018 European guidelines, which recommend treating grade II/III hypertension to target blood pressure (BP) within 3 months. The earliest LVH regression to date was demonstrated by echocardiography at 24 weeks. The effect of a rapid guideline-based treatment protocol on LV remodelling, with very early BP control by 18 weeks remains controversial and previously unreported. We aimed to determine whether such rapid hypertension treatment is associated with improvements in LV structure and function through paired cardiovascular magnetic resonance (CMR) scanning at baseline and 18 weeks, utilising CMR mass and feature tracking analysis. Methods We recruited participants with never-treated grade II/III hypertension, initiating a guideline-based treatment protocol which aimed to achieve BP control within 18 weeks. CMR and feature tracking were used to assess myocardial morphology and function immediately before and after treatment. Results We acquired complete pre- and 18-week post-treatment data for 41 participants. During the interval, LV mass index reduced significantly (43.5 ± 9.8 to 37.6 ± 8.3 g/m2, p Conclusions LVH regresses following just 18 weeks of intensive antihypertensive treatment in subjects with newly-diagnosed grade II/III hypertension. This is accompanied by potentially advantageous functional changes within the myocardium and supports the hypothesis that rapid treatment of hypertension could improve clinical outcomes. Trial registration: ISRCTN registry number: 57475376 (assigned 25/06/2015).

Supplemental Digital Content is available in the text., Background: Physiological assessment with pressure wire pullback can characterize coronary artery disease (CAD) with a focal or diffuse pattern. However, the clinical relevance of this distinction is unknown. We use data from the ORBITA trial (Objective Randomised Blinded Investigation With Optimal Medical Therapy of Angioplasty in Stable Angina) to test if the pattern of CAD predicts the placebo-controlled efficacy of percutaneous coronary intervention (PCI) on stress echocardiography ischemia and symptom end points. Methods: One hundred sixty-four patients in ORBITA underwent blinded instantaneous wave-free ratio (iFR) pullback assessment before randomization. Focal disease was defined as a ≥0.03 iFR unit drop within 15 mm, rather than over a longer distance. Analyses were performed using regression modeling. Results: In the PCI arm (n=85), 48 were focal and 37 were diffuse. In the placebo arm (n=79), 35 were focal and 44 were diffuse. Focal stenoses were associated with significantly lower fractional flow reserve (FFR) and iFR values than diffusely diseased vessels (mean FFR and iFR, focal 0.60±0.15 and 0.65±0.24, diffuse 0.78±0.10 and 0.88±0.08, respectively, P

Item does not contain fulltext OBJECTIVES: This study sought to evaluate sex differences in procedural characteristics and clinical outcomes of instantaneous wave-free ratio (iFR)- and fractional flow reserve (FFR)-guided revascularization strategies. BACKGROUND: An iFR-guided strategy has shown a lower revascularization rate than an FFR-guided strategy, without differences in clinical outcomes. METHODS: This is a post hoc analysis of the DEFINE-FLAIR (Functional Lesion Assessment of Intermediate stenosis to guide Revascularization) study, in which 601 women and 1,891 men were randomized to iFR- or FFR-guided strategy. The primary endpoint was 1-year major adverse cardiac events (MACE), a composite of all-cause death, nonfatal myocardial infarction, or unplanned revascularization. RESULTS: Among the entire population, women had a lower number of functionally significant lesions per patient (0.31 +/- 0.51 vs. 0.43 +/- 0.59; p < 0.001) and less frequently underwent revascularization than men (42.1% vs. 53.1%; p < 0.001). There was no difference in mean iFR value according to sex (0.91 +/- 0.09 vs. 0.91 +/- 0.10; p = 0.442). However, the mean FFR value was lower in men than in women (0.83 +/- 0.09 vs. 0.85 +/- 0.10; p = 0.001). In men, an FFR-guided strategy was associated with a higher rate of revascularization than an iFR-guided strategy (57.1% vs. 49.3%; p = 0.001), but this difference was not observed in women (41.4% vs. 42.6%; p = 0.757). There was no difference in MACE rates between iFR- and FFR-guided strategies in both women (5.4% vs. 5.6%, adjusted hazard ratio: 1.10; 95% confidence interval: 0.50 to 2.43; p = 0.805) and men (6.6% vs. 7.0%, adjusted hazard ratio: 0.98; 95% confidence interval: 0.66 to 1.46; p = 0.919). CONCLUSIONS: An FFR-guided strategy was associated with a higher rate of revascularization than iFR-guided strategy in men, but not in women. However, iFR- and FFR-guided strategies showed comparable clinical outcomes, regardless of sex. (Functional Lesion Assessment of Intermediate Stenosis to guide Revascularization [DEFINE-FLAIR]; NCT02053038).

PURPOSE OF REVIEW Although sound physiological principles and surgical precedent underpin renal denervation as a therapy for treatment resistant hypertension, and early clinical studies had produced encouraging results, the first sham-controlled study (SYMPLICITY HTN-3) failed to achieve its primary efficacy endpoint. Lessons learnt from this trial, and the knowledge derived from further animal and autopsy work, have been applied in three recently published sham-controlled trials. RECENT FINDINGS These trials - SPYRAL OFF-MED, RADIANCE SOLO and SPYRAL ON-MED - using newer technologies, demonstrate a 5-10 mmHg incremental reduction in ambulatory SBP from RDN against sham-control, in patients with mild-to-moderate hypertension taking 0-3 drugs. SUMMARY These results provide proof of principle of the blood pressure-lowering effect of renal denervation. We now require data on long-term safety and durability of the procedure. Research is needed to identify predictive markers of response as about one-third of subjects do not respond to renal denervation. Hard-outcome data would be welcome but might be difficult to acquire. Individuals with treatment resistance are obvious treatment candidates, but RDN may also potentially benefit those with medication nonadherence and/or intolerance and those unwilling to take pills.

Initial studies of catheter-based renal denervation (RDN) for uncontrolled HTN using radiofrequency ablation in the main renal arteries showed that RDN was effective in lowering office blood pressure (BP). However, the first randomized sham-controlled trial, SYMPLICITY-HTN-3, did not show significantly lower office or 24-h ambulatory systolic BP compared with sham treatment. Subsequent studies in both animals and humans demonstrated the potential importance of more distal and branch renal artery radiofrequency ablation, and a second-generation multielectrode system became available. Two recent randomized sham-controlled trials in patients not taking antihypertensive drugs (SPYRAL HTN-OFF MED) or continuing to take drugs (SPYRAL HTN-ON MED) performed RDN with the second-generation radiofrequency ablation system using an ablation protocol that included treatment of the distal renal artery as well as the branch renal arteries. These studies showed that RDN significantly reduced office and 24-h ambulatory BP compared with sham treatment. Another recent randomized sham-controlled trial in patients not receiving medications showed that RDN with catheter-based ultrasound (RADIANCE-HTN SOLO) applied in just the main renal arteries significantly lowered daytime ambulatory and office BP compared with sham treatment. These trials have renewed clinical and scientific interest in defining the appropriate role of RDN in hypertension treatment. In addition, other important issues will need to be addressed in the future such as the development of tests to determine the extent of RDN at the time of the procedure and the potential of renal nerve fibers to regain their patency at some later stage following the ablation procedure.

Objectives The aim of this study was to determine the lowest optimal tissue plasminogen activator (tPA) dose and delivery duration using ultrasound-facilitated catheter-directed thrombolysis (USCDT) for the treatment of acute intermediate-risk (submassive) pulmonary embolism. Background Previous trials of USCDT used tPA over 12 to 24 h at doses of 20 to 24 mg for acute pulmonary embolism. Methods Hemodynamically stable adults with acute intermediate-risk pulmonary embolism documented by computed tomographic angiography were randomized into this prospective multicenter, parallel-group trial. Patients received treatment with 1 of 4 USCDT regimens. The tPA dose ranged from 4 to 12 mg per lung and infusion duration from 2 to 6 h. The primary efficacy endpoint was reduction in right ventricular–to–left ventricular diameter ratio by computed tomographic angiography. A major secondary endpoint was embolic burden by refined modified Miller score, measured on computed tomographic angiography 48 h after initiation of USCDT. Results One hundred one patients were randomized, and improvements in right ventricular–to–left ventricular diameter ratio were as follows: arm 1 (4 mg/lung/2 h), 0.40 (24%; p = 0.0001); arm 2 (4 mg/lung/4 h), 0.35 (22.6%; p = 0.0001); arm 3 (6 mg/lung/6 h), 0.42 (26.3%; p = 0.0001); and arm 4 (12 mg/lung/6 h), 0.48 (25.5%; p = 0.0001). Improvement in refined modified Miller score was also seen in all groups. Four patients experienced major bleeding (4%). Of 2 intracranial hemorrhage events, 1 was attributed to tPA delivered by USCDT. Conclusions Treatment with USCDT using a shorter delivery duration and lower-dose tPA was associated with improved right ventricular function and reduced clot burden compared with baseline. The major bleeding rate was low, but 1 intracranial hemorrhage event due to tPA delivered by USCDT did occur.

Background: Dobutamine stress echocardiography is widely used to test for ischemia in patients with stable coronary artery disease. In this analysis, we studied the ability of the prerandomization stress echocardiography score to predict the placebo-controlled efficacy of percutaneous coronary intervention (PCI) within the ORBITA trial (Objective Randomised Blinded Investigation With Optimal Medical Therapy of Angioplasty in Stable Angina). Methods: One hundred eighty-three patients underwent dobutamine stress echocardiography before randomization. The stress echocardiography score is broadly the number of segments abnormal at peak stress, with akinetic segments counting double and dyskinetic segments counting triple. The ability of prerandomization stress echocardiography to predict the placebo-controlled effect of PCI on response variables was tested by using regression modeling. Results: At prerandomization, the stress echocardiography score was 1.56±1.77 in the PCI arm (n=98) and 1.61±1.73 in the placebo arm (n=85). There was a detectable interaction between prerandomization stress echocardiography score and the effect of PCI on angina frequency score with a larger placebo-controlled effect in patients with the highest stress echocardiography score ( P interaction =0.031). With our sample size, we were unable to detect an interaction between stress echocardiography score and any other patient-reported response variables: freedom from angina ( P interaction =0.116), physical limitation ( P interaction =0.461), quality of life ( P interaction =0.689), EuroQOL 5 quality-of-life score ( P interaction =0.789), or between stress echocardiography score and physician-assessed Canadian Cardiovascular Society angina class ( P interaction =0.693), and treadmill exercise time ( P interaction =0.426). Conclusions: The degree of ischemia assessed by dobutamine stress echocardiography predicts the placebo-controlled efficacy of PCI on patient-reported angina frequency. The greater the downstream stress echocardiography abnormality caused by a stenosis, the greater the reduction in symptoms from PCI. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02062593.

Recent prospective randomized clinical trials have demonstrated blood pressure lowering following renal denervation (RDN) with radiofrequency (RF) ablation systems and minimal adverse events in relatively small populations with short follow up duration. The current analysis estimates the rate of renal artery adverse events based on a comprehensive review of published reports. An online database search was performed to identify trials, registries and case reports that employed either the SYMPLICITY Flex or Spyral RF denervation systems (Medtronic, Santa Rosa, CA). Updated reviews of the SYMPLICITY HTN-3 trial and the Global SYMPLICITY Registry were also included. Renal artery stenoses classified as “significant”, greater than 50%, resulted in stent implant or if not specified were counted. The pooled incidence rate of stent implantation was determined by fixed-effects meta-analysis of the study-level incidence rates. Review of 45 published RDN trials reporting on procedural safety with 10,130 patient-years of follow up identified 0.44% of patients (25 of 5,657) with reported renal artery stenosis or dissection and 0.39% of patients (22 of 5,657) with required renal artery stenting. Meta-analysis of all reports indicated an 0.20% pooled annual incidence rate of stent implantation (95% CI: 0.11 to 0.29 % per patient-year). This result was consistent with a fixed effects Poisson regression model (0.22%; 95% CI: 0.14 to 0.32%). An additional 10 case reports including 11 patients with renal artery stenosis resulting in at least one stent implant were identified, with most cases diagnosed after recurrent hypertension, occasionally with concomitant symptoms. Median time from RDN procedure to all renal artery interventions, including both case reports and clinical trials, was 5.5 months (range: 0 to 33 months). A separate review of 14 clinical trials reporting on prospective follow up high resolution imaging of main renal arteries or branches using either MRI, CT or angiography following RDN found a new significant stenosis rate of 0.20% (one event out of 511 patients). Renal artery stenosis and re-intervention following renal denervation with the most commonly applied RF renal denervation system are rare.

Rapid treatment to target in hypertension may have beneficial effects on long-term outcomes. This has led to a new recommendation in the 2018 European hypertension guidelines for patients with grade II/III hypertension to be treated to target within three months. However, whether it is feasible and safe to quickly manage treatment-naive grade II/III hypertension to target was unclear. We examined this using a single-centre before and after interventional study, treating newly diagnosed, never-treated, grade II/III hypertensive patients with a daytime average systolic ABP ≥ 150 mmHg to target within 18 weeks. The proportion at office target BP at 18 weeks was determined, together with office and ambulatory BP change from baseline to after the intervention. The protocol was designed to maximise medication adherence, including a low threshold for treatment adaptation. Safety was evaluated through close monitoring of adverse events and protocol discontinuation. Fifty-five participants were enrolled with 54 completing the protocol. 69 ± 12.3% were at office target BP at their final visit, despite a high average starting BP of 175/103 mmHg, as a consequence of significant reductions in both office and ambulatory BP. Of those at office target BP, 51% were above target on ambulatory measurement. Adherence testing demonstrated that 92% of participants were adherent to treatment at their final visit. Therefore we conclude that the accelerated management of treatment-naive grade II/III hypertension is feasible and safe to implement in routine practice and there is no evidence to suggest it causes harm. Further large-scale randomised studies of rapid, adaptive treatment, including a cost-effectiveness analysis, are required.

Background: Accelerated tPA (tissue-type plasminogen activator) dosing regimens for ultrasound-facilitated, catheter-directed fibrinolysis improve short-term computed tomographic-measured right ventricular (RV)-to-left ventricular diameter ratio in massive and submassive pulmonary embolism. The impact on RV remodeling, functional status, and quality of life over the long-term remains unclear. Methods: To study 1-year changes in RV remodeling, functional status, and quality of life, we assessed patients with acute submassive pulmonary embolism randomly assigned to 1 of 4 tPA dosing regimens for ultrasound-facilitated, catheter-directed fibrinolysis in the OPTALYSE-PE trial (Optimum Duration and Dose of r-tPA With the Acoustic Pulse Thrombolysis Procedure for Intermediate-Risk Pulmonary Embolism; 8 mg/2 hours, 8 mg/4 hours, 12 mg/6 hours, and 24 mg/6 hours). Echocardiographic assessment included RV-to-left ventricular diameter ratio within 4 hours of treatment end, and at 48 hours, 30 days, 90 days, and 1 year. Functional status was assessed by 6-minute walk test at 30 days, 90 days, and 1 year and PROMIS-PF-6b scores at 30 days, 90 days, 180 days, 270 days, and 1 year. Quality of life was evaluated by PEmb-QOL scores at 30 days, 90 days, 180 days, 270 days, and 1 year. Results: Mean RV-to-left ventricular diameter ratio decreased from baseline to 4 hours and further at 48 hours and 30 days, with reductions maintained at 90 days and 1 year in all groups. Mean 6-minute walk distance, PROMIS-PF-6b, and PEmb-QOL scores improved over the course of 1 year in all groups. Conclusions: Accelerated lower-dose tPA regimens for ultrasound-facilitated, catheter-directed fibrinolysis resulted in sustained recovery of RV-to-left ventricular diameter ratio and tricuspid annular plane systolic excursion and improvements in functional status and quality of life over 1 year. Registration: URL: https://www.ClinicalTrials.gov . Unique Identifier: NCT02396758.

OBJECTIVES: We sought to assess the validity of the DILEMMA score against instantaneous wave-free ratio (iFR) and evaluate its utility in rationalizing the number of patients referred for invasive physiological assessment. BACKGROUND: The DILEMMA score is a validated angiographic scoring tool incorporating minimal lumen diameter, lesion length and subtended myocardial area that has been shown to predict the functional significance of lesions as assessed by fractional flow reserve (FFR). METHODS: Patients in the DEFINE-FLAIR study who had coronary stenosis of intermediate severity were randomized to either FFR or iFR. DILEMMA score was calculated retrospectively on a subset of this cohort by operators blinded to FFR or iFR values. RESULTS: Three hundred and forty-six lesions (181 assessed by FFR; 165 by iFR) from 259 patients (mean age 66.0 years, 79% male) were included. A DILEMMA score ≤ 2 had a negative predictive value of 96.3% and 95.7% for identifying lesions with FFR >0.80 and iFR >0.89, respectively. A DILEMMA score ≥ 9 had a positive predictive value of 88.9% and 100% for identifying lesions with FFR ≤0.80 and iFR ≤0.89, respectively. The receiver operating characteristic area under the curve values for DILEMMA score to predict FFR ≤0.80 and iFR ≤0.89 were 0.83 (95% CI 0.77–0.90) and 0.82 (0.75–0.89) respectively. A DILEMMA score ≤ 2 or ≥9 occurred in 172 of the 346 lesions (49.7%). CONCLUSIONS: Using DILEMMA score in patients with coronary stenosis of intermediate severity may reduce the need for pressure wire use, offering potential cost-savings and minimizing the risks associated with invasive physiological lesion assessment.

OBJECTIVES: The authors sought to evaluate the accuracy of instantaneous wave-Free Ratio (iFR) pullback measurements to predict post-percutaneous coronary intervention (PCI) physiological outcomes, and to quantify how often iFR pullback alters PCI strategy in real-world clinical settings.\ud \ud BACKGROUND: In tandem and diffuse disease, offline analysis of continuous iFR pullback measurement has previously been demonstrated to accurately predict the physiological outcome of revascularization. However, the accuracy of the online analysis approach (iFR pullback) remains untested.\ud \ud METHODS: Angiographically intermediate tandem and/or diffuse lesions were entered into the international, multi-center iFR GRADIENT (Single instantaneous wave-Free Ratio Pullback Pre-Angioplasty Predicts Hemodynamic Outcome Without Wedge Pressure in Human Coronary Artery Disease) registry. Operators were asked to submit their procedural strategy after angiography alone and then after iFR-pullback measurement incorporating virtual PCI and post-PCI iFR prediction. PCI was performed according to standard clinical practice. Following PCI, repeat iFR assessment was performed and the actual versus predicted post-PCI iFR values compared.\ud \ud RESULTS: Mean age was 67+/-12 years (81% male). Paired pre-and post-PCI iFR were measured in 128 patients (134 vessels). The predicted post-PCI iFR calculated online was 0.93+/-0.05; observed actual iFR was 0.92+/-0.06. iFR pullback predicted the post-PCI iFR outcome with 1.4+/-0.5% error. In comparison to angiography-based decision making, after iFR pullback, decision making was changed in 52 (31%) of vessels; with a reduction in lesion number (-0.18+/-0.05 lesion/vessel; p = 0.0001) and length (-4.4+/-1.0 mm/vessel; p < 0.0001).\ud \ud CONCLUSIONS: In tandem and diffuse coronary disease, iFR pullback predicted the physiological outcome of PCI with a high degree of accuracy. Compared with angiography alone, availability of iFR pullback altered revascularization procedural planning in nearly one-third of patients.

Fractional flow reserve (FFR) has been shown to improve outcomes when used to guide percutaneous coronary intervention (PCI). There have been two proposed cut-off points for FFR. The first was derived by comparing FFR against a series of non-invasive tests, with a value of ≤0.75 shown to predict a positive ischaemia test. It was then shown in the DEFER study that a vessel FFR value of ≥0.75 was associated with safe deferral of PCI. During the validation phase, a ‘grey zone’ for FFR values of between 0.76 and 0.80 was demonstrated, where a positive non-invasive test may still occur, but sensitivity and specificity were sub-optimal. Clinical judgement was therefore advised for values in this range. The FAME studies then moved the FFR cut-off point to ≤0.80, with a view to predicting outcomes. The ≤0.80 cut-off point has been adopted into clinical practice guidelines, whereas the lower value of ≤0.75 is no longer widely used. Here, the authors discuss the data underpinning these cut-off values and the practical implications for their use when using FFR guidance in PCI.

OBJECTIVES The aim of this study was to investigate the clinical outcomes of patients deferred from coronary revascularization on the basis of instantaneous wave-free ratio (iFR) or fractional flow reserve (FFR) measurements in stable angina pectoris (SAP) and acute coronary syndromes (ACS). BACKGROUND Assessment of coronary stenosis severity with pressure guidewires is recommended to determine the need for myocardial revascularization. METHODS The safety of deferral of coronary revascularization in the pooled per-protocol population (n = 4,486) of the DEFINE-FLAIR (Functional Lesion Assessment of Intermediate Stenosis to Guide Revascularisation) and iFR-SWEDEHEART (Instantaneous Wave-Free Ratio Versus Fractional Flow Reserve in Patients With Stable Angina Pectoris or Acute Coronary Syndrome) randomized clinical trials was investigated. Patients were stratified according to revascularization decision making on the basis of iFR or FFR and to clinical presentation (SAP or ACS). The primary endpoint was major adverse cardiac events (MACE), defined as the composite of all-cause death, nonfatal myocardial infarction, or unplanned revascularization at 1 year. RESULTS Coronary revascularization was deferred in 2,130 patients. Deferral was performed in 1,117 patients (50%) in the iFR group and 1,013 patients (45%) in the FFR group (p amp;lt; 0.01). At 1 year, the MACE rate in the deferred population was similar between the iFR and FFR groups (4.12% vs. 4.05%; fully adjusted hazard ratio: 1.13; 95% confidence interval: 0.72 to 1.79; p = 0.60). A clinical presentation with ACS was associated with a higher MACE rate compared with SAP in deferred patients (5.91% vs. 3.64% in ACS and SAP, respectively; fully adjusted hazard ratio: 0.61 in favor of SAP; 95% confidence interval: 0.38 to 0.99; p = 0.04). CONCLUSIONS Overall, deferral of revascularization is equally safe with both iFR and FFR, with a low MACE rate of about 4%. Lesions were more frequently deferred when iFR was used to assess physiological significance. In deferred patients presenting with ACS, the event rate was significantly increased compared with SAP at 1 year. (C) 2018 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. Funding Agencies|Philips; Upsala Clinical Research Centre; Volcano; Imperial College; Philips Volcano; Imperial College London; Medical Research Council

OBJECTIVES The aim of this double-blind, randomized, sham-controlled study was to verify the blood pressure (BP)-lowering efficacy of externally delivered focused ultrasound for renal denervation (RDN). BACKGROUND Nonrandomized, first proof-of-concept study and experimental evidence suggested that noninvasive techniques of RDN emerged as an alternative approach of RDN to invasive technologies. METHODS WAVE IV, an international, randomized (1 : 1) sham-controlled, double-blind prospective clinical study, was prematurely stopped. Patients were enrolled if office BP was at least 160 mmHg and 24-h ambulatory BP was at least 135 mmHg, while taking three or more antihypertensive medications. The treatment consisted of bilateral RDN using therapeutic levels of ultrasound energy and the sham consisted of bilateral application of diagnostic levels of ultrasound energy. RESULTS In the 81 treated patients neither changes in office BP at 12 and 24 weeks, nor changes in 24-h ambulatory BP at 24-week follow-up visit differed between the two groups significantly. Of note, no safety signal was observed. Adherence analysis disclosed full adherence in 77% at baseline and 82% at 6 months' follow-up visit. Post hoc analysis revealed that stricter criteria for stabilization of BP at baseline were associated with a numerically greater change in 24-h ambulatory BP in the RDN group than in the sham group. CONCLUSION Our data did not prove that antihypertensive efficacy of the externally delivered focused ultrasound for RDN was greater than the sham effect. Stabilization of BP at baseline was identified as an important determinant of BP changes.

BACKGROUND: Coronary revascularization guided by fractional flow reserve (FFR) is associated with better patient outcomes after the procedure than revascularization guided by angiography alone. It is unknown whether the instantaneous wave-free ratio (iFR), an alternative measure that does not require the administration of adenosine, will offer benefits similar to those of FFR. METHODS: We randomly assigned 2492 patients with coronary artery disease, in a 1:1 ratio, to undergo either iFR-guided or FFR-guided coronary revascularization. The primary end point was the 1-year risk of major adverse cardiac events, which were a composite of death from any cause, nonfatal myocardial infarction, or unplanned revascularization. The trial was designed to show the noninferiority of iFR to FFR, with a margin of 3.4 percentage points for the difference in risk. RESULTS: At 1 year, the primary end point had occurred in 78 of 1148 patients (6.8%) in the iFR group and in 83 of 1182 patients (7.0%) in the FFR group (difference in risk, -0.2 percentage points; 95% confidence interval [CI], -2.3 to 1.8; P

Objectives To evaluate the first experience of real-time instantaneous wave–free ratio (iFR) measurement by clinicians. Background The iFR is a new vasodilator-free index of coronary stenosis severity, calculated as a trans-lesion pressure ratio during a specific period of baseline diastole, when distal resistance is lowest and stable. Because all previous studies have calculated iFR offline, the feasibility of real-time iFR measurement has never been assessed. Methods Three hundred ninety-two stenoses with angiographically intermediate stenoses were included in this multicenter international analysis. Instantaneous wave–free ratio and fractional flow reserve (FFR) were performed in real time on commercially available consoles. The classification agreement of coronary stenoses between iFR and FFR was calculated. Results Instantaneous wave–free ratio and FFR maintain a close level of diagnostic agreement when both are measured by clinicians in real time (for a clinical 0.80 FFR cutoff: area under the receiver operating characteristic curve [ROCAUC] 0.87, classification match 80%, and optimal iFR cutoff 0.90; for a ischemic 0.75 FFR cutoff: iFR ROCAUC 0.90, classification match 88%, and optimal iFR cutoff 0.85; if the FFR 0.75-0.80 gray zone is accounted for: ROCAUC 0.93, classification match 92%). When iFR and FFR are evaluated together in a hybrid decision-making strategy, 61% of the population is spared from vasodilator while maintaining a 94% overall agreement with FFR lesion classification. Conclusion When measured in real time, iFR maintains the close relationship to FFR reported in offline studies. These findings confirm the feasibility and reliability of real-time iFR calculation by clinicians., Graphical Abstract

Objectives To report very long-term follow-up of “Full-Metal Jacket” (FMJ) percutaneous coronary interventions (PCI) in long-diffuse coronary lesions with drug-eluting stents (DES). Background PCI for long-diffuse lesions may result in FMJ, which is not preferred by some operators due to long-term risk of restenosis and stent thrombosis. The data on long-term follow-up of patients with FMJ are limited and would be useful in understanding the safety and feasibility of such a strategy. Methods Between April 2002 and March 2007, 274 patients (297 lesions in native coronary arteries) underwent PCI utilizing DES. FMJ was described as lesions requiring ≥ 60 mm of continuous stent. The measured endpoints were cardiac death, target-vessel myocardial infarction (MI), target lesion revascularization (TLR), target-vessel revascularization (TVR), and major adverse cardiac events (MACE) defined as composite of cardiac death, target-vessel MI, and TVR. Results The mean age of patients was 62.1 ± 11 years. The mean length of total stents used was 75.1 ± 16.4 mm (60–150). During the median follow-up of 74.7 months (interquartile range: 58–96), the rates of cardiac death, MI, TLR, and TVR were: 5.8% (n = 16), 6.2% (n = 17), 27.3% (n = 81), and 30% (n = 89), respectively. The MACE rate was 34%. Definite and probable stent thrombosis occurred in 10 patients (3.6%). Conclusion The long-term follow-up of patients with FMJ is acceptable especially in regards to hard endpoints (death and MI) given the complexity of lesions treated. The high MACE rate was driven mainly by TVR. The availability of newer-generation DES and bioabsorbable scaffolds may improve these results. © 2014 Wiley Periodicals, Inc.

Surgical aortic valve replacement remains the gold standard for the treatment of severe, symptomatic aortic stenosis. However, percutaneous treatments are challenging this paradigm in high-risk surgical patients. Technological developments have been rapid in the field of percutaneous aortic valve intervention. Two devices have been approved for general use in Europe: the Edwards SAPIEN valve (Edwards Lifesciences, Irvine, CA) and the CoreValve ReValving((R)) System (CoreValve ReValving((R)) Technology Medtronic Inc., Minneapolis, MN), with 15 potential new designs for percutaneous aortic valves in development around the world. Both systems can be delivered via the transfemoral, transapical and the axillary/subclavian routes, depending upon patient characteristics, anatomy, and the device available to the operator. Careful selection of appropriate patients is essential to ensure a safe procedure. This necessitates a multidisciplinary approach, with multiple imaging modalities used to fully delineate the peripheral vasculature, aortic anatomy and the valve itself. It is important to remember, however, that just because we can treat aortic valve disease percutaneously, it does not mean that we necessarily should. The gold standard treatment for aortic stenosis remains thoracotomy and surgical replacement of the valve; to this end it is essential that surgeons play a central role in the decision-making processes for transcatheter aortic valve implantation and that they embrace this new and exciting technology, which promises to dramatically change the way their high-risk aortic valve patients are managed over the course of the next 10 years.

Objectives We hypothesized that an amlodipine-based regimen would have more favorable effects on left ventricular (LV) diastolic function. Background Different antihypertensive therapies may vary in their effect on LV diastolic function. Methods The HACVD (Hypertension Associated Cardiovascular Disease) substudy of ASCOT (Anglo-Scandinavian Cardiac Outcomes Trial) collected detailed cardiovascular phenotypic data on a subset of 1,006 participants recruited from 2 centers (St. Mary's Hospital, London, and Beaumont Hospital, Dublin). Conventional and tissue Doppler echocardiography and measurement of plasma B-type natriuretic peptide (BNP) were performed approximately 1 year after randomization to atenolol-based or amlodipine-based antihypertensive treatment to assess LV diastolic function. Results On-treatment blood pressure (BP) (mean ± SD) was similar in both groups: atenolol-based regimen, systolic BP of 137 ± 17 mm Hg, diastolic BP of 82 ± 9 mm Hg; amlodipine-based regimen, systolic BP of 136 ± 15 mm Hg, diastolic BP of 80 ± 9 mm Hg. Ejection fraction did not differ between groups, but early diastolic mitral annular velocity (E′), a measure of diastolic relaxation, was lower in patients on the atenolol-based regimen: atenolol-based regimen, 7.9 ± 1.8; amlodipine-based regimen, 8.8 ± 2.0. A measure of left ventricular filling pressure, E/E′, and BNP were significantly higher in patients on the atenolol-based regimen. Differences in E′, E/E′, and BNP remained significant after adjustment for age and sex. Further adjustment for systolic BP, LV mass index, and heart rate had no impact on differences in mean E′ or BNP. The difference in E/E′ was attenuated. Conclusions Patients receiving treatment with an amlodipine-based regimen had better diastolic function than patients treated with the atenolol-based regimen. Treatment-related differences in diastolic function were independent of BP reduction and other factors that are known to affect diastolic function.

Objectives The aim of this study was to evaluate the efficacy and safety of unrestricted everolimus-eluting stent (EES) implantation in a contemporary cohort of real-world patients. Background The randomized SPIRIT (A Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System in the Treatment of Patients With de Novo Native Coronary Artery Lesions) trials have evaluated the performance of EES, resulting in their approval by the Food and Drug Administration, but data regarding unselected usage, including off-label indications are lacking. Methods Consecutive patients treated with EES (either PROMUS, Boston Scientific Corp., Natick, Massachusetts, or XIENCE-V, Abbott Vascular Devices, Santa Clara, California) between October 2006 and February 2008 were analyzed. End points were cardiac death, myocardial infarction (MI), ischemic-driven target lesion revascularization (TLR), stent thrombosis (ST), and major adverse cardiac events (MACE) (a composite of cardiac death, MI, TLR) during follow-up. Results We identified 345 patients (573 lesions) treated with EES. The majority of patients (71.9%) were treated for ≥1 off-label or untested indication. Clinical follow-up was completed in 99%. At a median follow-up of 378 days (interquartile range 334 to 473), MACE occurred in 36 (10.6%) patients, TLR in 27 (7.9%), MI in 7 (2.1%), and cardiac death in 7 (2.1%). Definite and probable ST was observed in 3 (0.9%) cases. Off-label EES implantation was not associated with a statistically significant increased risk of MACE (12.2% vs. 6.3%, p = 0.17), TLR (9.3% vs. 4.2%, p = 0.18), or ST (0.8% vs. 1.1%, p = 1.0). On multivariable analysis, previous bypass surgery (p = 0.002) and diabetes (p = 0.03) were associated with MACE. Conclusions In unrestricted daily practice, EES were implanted predominantly for off-label indications and associated with a relative low rate of MACE and TLR.

Patients with controlled hypertension are at risk of future cardiac events, but predicting first events remains difficult. We hypothesized that modern echocardiographic measures of left ventricular diastolic function may be more sensitive than traditional echocardiographic methods of risk prediction and set out to test this in a cohort of patients with well-controlled hypertension.Conventional and tissue Doppler echocardiography was performed on 980 participants in the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT). All subjects had hypertension, but no known cardiac disease. Cardiac events were defined as fatal and non-fatal myocardial infarction (including silent myocardial infarction), coronary revascularization procedures, new-onset angina (stable or unstable), fatal and non-fatal heart failure, and life-threatening arrhythmias. Analysis was performed by a single, blinded observer. There were 56 primary cardiac events during 4.2 +/- 0.7 years follow-up. The ratio of transmitral Doppler early filling velocity to tissue Doppler early diastolic mitral annular velocity (E/E') was the strongest predictor of first cardiac events in Cox-proportional hazards models. Following adjustment for covariates, a unit rise in the E/E' ratio was associated with a 17% increment in risk of a cardiac event (HR 1.17, CI 1.05-1.29; P = 0.003).Tissue Doppler E/E', a non-invasive estimate of left atrial filling pressure, independently predicts primary cardiac events in a hypertensive population and out-performed traditional echocardiographic measures in this moderately sized, well-treated hypertensive population. E/E' represents a simple, effective tool for assessing cardiac risk in a hypertensive population.

Background— Limited long-term data exist on patients who have undergone drug-eluting stenting of very long lesions (requiring ≥60 mm of continuous stent) in native coronary arteries (“full-metal jacket”). Methods and Results— We examined consecutive procedures taking place between March 2002 and 2007 at 2 high-volume centers in Milan, Italy. Exclusion criteria were percutaneous coronary intervention for restenosis, percutaneous coronary intervention to a bypass graft, or percutaneous coronary intervention for acute ST-elevation myocardial infarction (MI). We identified 658 full-metal jacket lesions in 617 patients. Average age of the cohort was 62.0�10.6; 32.8% were diabetic, 51.5% had a previous MI, and 33.4% had undergone a previous percutaneous transluminal coronary angioplasty. Mean ejection fraction was 52.1�10.4%. The lesion was a chronic total occlusion in 33.0%. Median duration of clinical follow-up was 39 months (interquartile range, 28 to 50). Six-month follow-up was achieved in 97% of patients; 2-year follow-up was achieved in 91%. All-cause mortality rate was 7.3%; cardiac death rate was 3.6%. Non–procedure-related MI rates were 3.5%. Target lesion revascularization rates were 23.4%. There were 17 cases of Academic Research Consortium–defined definite or probable stent thrombosis (2.6%): 5 acute, 2 subacute, 6 late, and 4 very late. Ten of the 17 cases occurred while the patient was receiving dual antiplatelet therapy; 4 of the 17 after premature termination of 1 or both antiplatelets, and 3 of the 17 occurred while the patient was receiving single-antiplatelet therapy, after having completed the prescribed course of dual antiplatelet therapy. Conclusion— When very long lesions (≥60 mm) were treated using overlapping drug-eluting stents, 23.4% required a further procedure for restenosis at 3-year follow-up. However, MI, stent thrombosis, and cardiac mortality rates were relatively low.

Objectives We investigated whether diastolic function differs between hypertensive patients of African-Caribbean or white European origin and established whether differences could be explained by confounding variables. Background African Caribbeans are known to have a higher prevalence of heart failure than white Europeans but it is unclear whether this is a result of known risk factors. Tissue Doppler technology now allows accurate quantification of diastolic function, which is recognized as an important factor in the development of heart failure. Methods Participants from a single center participating in the ASCOT (Anglo-Scandinavian Cardiac Outcomes Trial), composed of patients with hypertension but no evidence of heart failure, were studied. Left ventricular structure and function were measured in 509 patients using conventional and tissue Doppler echocardiography. Diastolic function was assessed using the tissue Doppler early diastolic velocity E′ (averaged from 3 left ventricular segments) and the ratio of this and the transmitral early filling velocity E (E/E′). Results In African-Caribbean patients, mean E′ was significantly lower (7.7 cm/s vs. 8.6 cm/s, p = 0.003) and mean E/E′ was significantly higher (8.85 vs. 7.93, p = 0.003). After adjustment for confounding variables—age, gender, systolic blood pressure, pulse pressure, cholesterol, smoking, ejection fraction, left ventricular mass index, and diabetes mellitus—the effect of African-Caribbean ethnicity on diastolic function remained highly significant (E′: 7.52 vs. 8.51; p Conclusions Diastolic function is significantly worse in hypertensive patients of African-Caribbean origin than in white Europeans. This difference in diastolic performance is not due to known confounding variables.

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 0.2). 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. Electronic supplementary material The online version of this article (doi:10.1007/s00392-015-0959-4) contains supplementary material, which is available to authorized users.

Background: In tandem and diffuse disease, offline analysis of continuous instantaneous wave-free ratio (iFR) pullback measurement has been demonstrated to accurately predict the physiological outcome of revascularization. However, the accuracy of the real-time online analysis approach (iFR Scout)

Antihypertensive treatment can improve tissue Doppler indices of left ventricular diastolic function in the short term, but little is known about the longer-term effect of different antihypertensive treatments on progression of left ventricular diastolic function and left ventricular hypertrophy. We hypothesized that long-term treatment of hypertension will lead to improvements in left ventricular hypertrophy and diastolic function. We collected detailed cardiovascular phenotypic data on 1006 participants from a substudy of the Anglo-Scandinavian Cardiac Outcomes Trial. Patients randomized to either an amlodipine±perindopril-based or an atenolol±bendroflumethiazide-based regimen underwent conventional and tissue Doppler echocardiography at time of control of blood pressure after randomization (≈1.5 years; phase 1) and after a further 2 years of antihypertensive treatment (phase 2). There were no prerandomization data. Five hundred thirty-six patients had complete data collection at both phases. Left ventricular mass index regressed from phase 1 to 2 with no significant difference between treatment groups (amlodipine: 119.5–116.8; atenolol: 122.9–117.5; P P =not significant), but deteriorated in the atenolol±bendroflumethiazide-based regimen (E/e′, 8.0–8.5 cm/s; P

Background Stent thrombosis (ST) and restenosis are concerns after percutaneous coronary intervention (PCI). Limited information exists concerning clinical and angiographic outcomes following multiple stent insertion. We therefore present the long-term outcome from drug-eluting stent (DES) insertion and correlate this with the Syntax score. Methods and Results Between April 2002 and 2006, all patients that underwent multilesion PCI (defined as ≥4 DES) were included for analysis, and follow-up commenced from the point where the fourth stent was inserted. Three hundred and seventy-four patients were identified, comprising 1972 lesions; 99% had clinical (30±16 months), and 72% had angiographic follow-up. The mean number of stents implanted was 5.7±1.9 and with length of 137±50 mm and Syntax Score of 24±8. The Syntax score (SS) did not predict major adverse cardiac events (MACE) at long-term follow-up, which occurred in 33% in the low SS ( 33); P =ns. However, the number of stents implanted correlated with events [MACE: 12% (4 DES), 35% (4–6 DES), 61% (>6 DES)]. There were 11 (2.9%) definite and probable ST: four acute and subacute, three late, and four very late. Conclusions This study demonstrates an acceptable occurrence of myocardial infarction, death, repeat revascularisation, and ST in patients with multivessel de novo lesions, which had better correlation with the number of DES inserted than the Syntax score.

There exist case reports of using transcatheter aortic valves to treat dysfunctional surgically implanted aortic bioprosthesis. There are also case series reported of transaxillary implantation of the CoreValve device to treat Aortic Stenosis. In this article, we report the successful implantation an Edwards Sapien 23mm transcatheter aortic valve through the left axillary artery, in a patient with a functioning LIMA graft in order to treat a severely regurgitant Freestyle 23mm aortic bioprosthesis. © 2009 Wiley-Liss, Inc.

Introduction: Intra-aortic balloon pumping is widely used to augment diastolic coronary perfusion. However, far less is known about its effects on other large arteries. In this study we assessed the effects of intra-arterial balloon pump pressure support on pressure and flow in the proximal aorta, carotid, coronary and renal arteries. Methods: Recordings of simultaneous pressure and flow velocity were made using intra-arterial sensor tipped wires. Velocity time integral (VTI) was calculated at each location. Results: With balloon pump support VTI increased in the coronary arteries (458 to 540cm, 15%). In contrast, in the carotid arteries VTI markedly decreased (278 to 228cm, −21%). VTI remained constant in the renal arteries (247cm) and the aorta (225cm). The detrimental reduction in carotid VTI was due to the sudden fall in pressure occurring with balloon deflation, which results in carotid velocity transiently becoming negative (Fig. 1). Figure 1Pressure and velocity in the carotid artery before (left) and during (right) intra-arterial balloon pump support. Conclusion: Intra-arterial balloon pumping augments coronary blood flow, at the expense of diminishing carotid blood flow. This could lead to cerebral insufficiency in patients with obstructive carotid disease.

Transcatheter aortic valve implantation is an alternative to conventional aortic valve replacement for patients at high surgical risk, with favorable procedural outcomes. Aortic regurgitation remains an off-label indication. Recent case reports describe the successful use of a second CoreValve inside a malpositioned first CoreValve. In the current case, we report for the first time a valve-in-valve procedure for the treatment of a severely insufficient CoreValve prosthesis using the Edwards-Sapien prosthesis. © 2009 Wiley-Liss, Inc.

Brain natriuretic peptide (BNP) is a cardiac neurohormone of increasing interest over recent years, with research applications expanding at a rapid rate and new data published on a monthly basis. Initially developed as a diagnostic aid for those with acute shortness of breath, clinical applications are now increasing, and this article reviews these clinical applications of BNP and the evidence for effectiveness of the synthetic BNP analogue nesiritide.

Left ventricular hypertrophy (LVH) is more than just an adaptive response to hypertension. It predicts a poor prognosis independently of the blood pressure (BP) level. There is increasing evidence from studies such as Heart Outcomes Prevention Evaluation (HOPE) and Losartan Intervention For Endpoint reduction in hypertension (LIFE) that LVH should be a target for treatment, above and beyond BP control. It is likely that drugs blocking the renin-angiotensin-aldosterone system cause greater regression of LVH than other agents and this is probably the mechanism that explains the superiority of losartan over atenolol in the LIFE study. In order to achieve the stringent BP goals suggested by modern guidelines, most patients will require multiple antihypertensive agents and the clinical choices relate more often to which combinations of drugs are most appropriate, rather than which single drug is the best. Tight BP control should be the first priority and this is likely to lead to regression of LVH.

A 58-year-old man presented to his local doctor with 30 min of chest pain and inferior ST-segment elevation on his ECG ( Panel A ). He was transferred immediately for primary angioplasty. On arrival, his ECG became normal and pain had eased ( Panel B ). Left coronary injection ( Panel C ) showed a 70% stenosis of the posterolateral branch of the …

Background Dual anti-platelet therapy with aspirin and a thienopyridine (DAT) is used to prevent stent thrombosis after percutaneous coronary intervention (PCI). Low response to clopidogrel therapy (LR) occurs, but laboratory tests have a controversial role in the identification of this condition. Methods We studied LR in patients with stable angina undergoing elective PCI, all on DAT for at least 7 days, by comparing: 1) Flow cytometry (FC) to measure platelet membrane expression of P-selectin (CD62P) and PAC-1 binding following double stimulation with ADP and collagen type I either in the presence of prostaglandin (PG) E1; 2) VerifyNow-P2Y12 test, in which results are reported as absolute P2Y12-Reaction-Units (PRU) or % of inhibition (% inhibition). Results Thirty controls and 52 patients were analyzed. The median percentage of platelets exhibiting CD62P expression and PAC-1 binding by FC evaluation after stimulation in the presence of PG E1 was 25.4% (IQR: 21.4–33.1%) and 3.5% (1.7–9.4%), respectively. Only 6 patients receiving DAT (11.5%) had both values above the 1st quartile of controls, and were defined as LR. Evaluation of the same patients with the VerifyNow-P2Y12 test revealed that the area under the receiver-operating-characteristic (ROC) curve was 0.94 (95% CI: 0.84–0.98, p < 0.0001) for % inhibition and 0.85 (0.72–0.93, p < 0.005) for PRU. Cut-off values of ≤ 15% inhibition or > 213 PRU gave the maximum accuracy for the detection of patients defined as having LR by FC. Conclusion In conclusion our findings show that a cut-off value of ≤ 15% inhibition or > 213 PRU in the VerifyNow-P2Y12 test may provide the best accuracy for the identification of patients with LR.