David E. Kandzari

Catheter-based renal denervation in patients with uncontrolled hypertension in the absence of antihypertensive medications (SPYRAL HTN-OFF MED): a randomised, sham-controlled, proof-of-concept trial

BACKGROUNDnPrevious randomised renal denervation studies did not show consistent efficacy in reducing blood pressure. The objective of our study was to evaluate the effect of renal denervation on blood pressure in the absence of antihypertensive medications.nnnMETHODSnSPYRAL HTN-OFF MED was a multicentre, international, single-blind, randomised, sham-controlled, proof-of-concept trial. Patients were enrolled at 21 centres in the USA, Europe, Japan, and Australia. Eligible patients were drug-naive or discontinued their antihypertensive medications. Patients with an office systolic blood pressure (SBP) of 150 mm Hg or greater and less than 180 mm Hg, office diastolic blood pressure (DBP) of 90 mm Hg or greater, and a mean 24-h ambulatory SBP of 140 mm Hg or greater and less than 170 mm Hg at second screening underwent renal angiography and were randomly assigned to renal denervation or sham control. Patients, caregivers, and those assessing blood pressure were blinded to randomisation assignments. The primary endpoint, change in 24-h blood pressure at 3 months, was compared between groups. Drug surveillance was done to ensure patient compliance with absence of antihypertensive medication. The primary analysis was done in the intention-to-treat population. Safety events were assessed at 3 months. This study is registered with ClinicalTrials.gov, number NCT02439749.nnnFINDINGSnBetween June 25, 2015, and Jan 30, 2017, 353 patients were screened. 80 patients were randomly assigned to renal denervation (n=38) or sham control (n=42) and followed up for 3 months. Office and 24-h ambulatory blood pressure decreased significantly from baseline to 3 months in the renal denervation group: 24-h SBP -5·5 mm Hg (95% CI -9·1 to -2·0; p=0·0031), 24-h DBP -4·8 mm Hg (-7·0 to -2·6; p<0·0001), office SBP -10·0 mm Hg (-15·1 to -4·9; p=0·0004), and office DBP -5·3 mm Hg (-7·8 to -2·7; p=0·0002). No significant changes were seen in the sham-control group: 24-h SBP -0·5 mm Hg (95% CI -3·9 to 2·9; p=0·7644), 24-h DBP -0·4 mm Hg (-2·2 to 1·4; p=0·6448), office SBP -2·3 mm Hg (-6·1 to 1·6; p=0·2381), and office DBP -0·3 mm Hg (-2·9 to 2·2; p=0·8052). The mean difference between the groups favoured renal denervation for 3-month change in both office and 24-h blood pressure from baseline: 24-h SBP -5·0 mm Hg (95% CI -9·9 to -0·2; p=0·0414), 24-h DBP -4·4 mm Hg (-7·2 to -1·6; p=0·0024), office SBP -7·7 mm Hg (-14·0 to -1·5; p=0·0155), and office DBP -4·9 mm Hg (-8·5 to -1·4; p=0·0077). Baseline-adjusted analyses showed similar findings. There were no major adverse events in either group.nnnINTERPRETATIONnResults from SPYRAL HTN-OFF MED provide biological proof of principle for the blood-pressure-lowering efficacy of renal denervation.nnnFUNDINGnMedtronic.

Application of the “Hybrid Approach” to Chronic Total Occlusions in Patients With Previous Coronary Artery Bypass Graft Surgery (from a Contemporary Multicenter US Registry)

Percutaneous coronary intervention (PCI) for chronic total occlusions (CTOs) has been traditionally associated with lower success rates in patients with previous coronary artery bypass graft surgery (CABG). We sought to examine the success and complication rates of CTO PCI using the hybrid crossing algorithm among patients with a history of previous CABG. The procedural outcomes of 496 consecutive CTO PCIs performed at 5 high-volume PCI centers in the United States from January 2012 to August 2013 were assessed. The outcomes of patients with previous CABG were compared with those of patients without previous CABG. Compared with patients without previous CABG (n = 320), patients with previous CABG (n = 176, 35%) were older, had more coronary artery disease risk factors, and had less favorable baseline angiographic CTO characteristics. Technical and procedural success was slightly lower among patients with previous CABG (88.1% vs 93.4%, p = 0.044 and 87.5 vs 92.5%, p = 0.07, respectively). Patients with previous CABG more commonly underwent CTO PCI using the retrograde approach (39% vs 24%, respectively, p <0.001) and received higher air kerma radiation exposure (4.8 [interquartile range 3.0 to 6.4] vs 3.1 [1.9 to 5.3] Gray, p <0.001) and fluoroscopy time (59 [38 to 77] vs 34 [21 to 55] minutes, p <0.001). Major procedural complications were similar in the 2 groups: 2 of 176 (1.1%) patients with previous CABG versus 7 of 320 (2.1%) patients without previous CABG (p = 0.40). In conclusion, with application of the hybrid approach to CTO PCI, success was slightly lower, and complication rates were similar between patients with and without previous CABG.

The efficacy of "hybrid" percutaneous coronary intervention in chronic total occlusions caused by in-stent restenosis: insights from a US multicenter registry.

To examine the success and complication rates in percutaneous coronary intervention (PCI) for chronic total occlusions (CTO) caused by in‐stent restenosis (ISR).

Transradial approach for coronary chronic total occlusion interventions: Insights from a contemporary multicenter registry

To examine the impact of transradial access on the procedural outcomes of chronic total occlusion (CTO) percutaneous coronary interventions (PCI).

Percutaneous Intervention of Circumflex Chronic Total Occlusions Is Associated With Worse Procedural Outcomes: Insights From a Multicentre US Registry

BACKGROUNDnWe sought to determine whether outcomes of chronic total occlusion (CTO) percutaneous coronary intervention (PCI) vary according to CTO target vessel: left anterior descending artery (LAD), left circumflex artery (LCX), and right coronary artery (RCA).nnnMETHODSnWe evaluated the clinical and angiographic characteristics and procedural outcomes of 636 patients who underwent CTO PCI at 6 high-volume centres in the United States between January 2012 and March 2014.nnnRESULTSnThe CTO target vessel was the RCA in 387 cases (61%), LAD in 132 (21%), and LCX in 117 (18%). LCX lesions were more tortuous and RCA lesions had greater occlusion length and Japanese Chronic Total Occlusion (J-CTO) score, but were less likely to have a side branch at the proximal cap and had more developed collateral circulation. The rate of procedural success was lower in LCX CTOs (84.6%), followed by RCA (91.7%), and LAD (94.7%) CTOs (P = 0.016). Major complications tended to occur more frequently in LCX PCI (4.3% vs 1.0% for RCA vs 2.3% for LAD; P = 0.07). LCX and RCA CTO PCI required longer fluoroscopy times (45 [interquartile range (IQR), 30-74] minutes vs 45 [IQR, 21-69] minutes for RCA vs 34 [IQR, 20-60] minutes for LAD; P = 0.018) and LCX CTOs required more contrast administration (280 [IQR, 210-370] mL vs 250 [IQR, 184-350] mL for RCA and 280 [IQR, 200-400] mL for LAD).nnnCONCLUSIONSnIn a contemporary, multicentre CTO PCI registry, LCX was the least common target vessel. Compared with LAD and RCA, PCI of LCX CTOs was associated with a lower rate of procedural success, less efficiency, and a nonsignificant trend for higher rates of complications.

Treatment of the chronic total occlusion: A call to action for the interventional community

There is substantial evidence that recanalization of a chronic total occlusion is beneficial; nonetheless, it is generally underutilized in clinical practice. We consider the Aesops fable of the “Fox and the Grapes” as analogous to the current situation in interventional cardiology. The technical challenges in achieving CTO recanalization has led interventionalists, clinical cardiologists, and sometimes even patients to believe that CTO recanalization is not effective, and, therefore, not needed. This perspective reviews available data regarding efficacy and safety of CTO percutaneous coronary intervention (PCI) in the current drug‐eluting stent era, discusses areas where more studies are required, and encourages the interventional community to utilize CTO PCI where appropriate based on current evidence.

Effect of renal denervation on blood pressure in the presence of antihypertensive drugs: 6-month efficacy and safety results from the SPYRAL HTN-ON MED proof-of-concept randomised trial

BACKGROUNDnPrevious catheter-based renal denervation studies have reported variable efficacy results. We aimed to evaluate safety and blood pressure response after renal denervation or sham control in patients with uncontrolled hypertension on antihypertensive medications with drug adherence testing.nnnMETHODSnIn this international, randomised, single-blind, sham-control, proof-of-concept trial, patients with uncontrolled hypertension (aged 20-80 years) were enrolled at 25 centres in the USA, Germany, Japan, UK, Australia, Austria, and Greece. Eligible patients had an office systolic blood pressure of between 150 mm Hg and 180 mm Hg and a diastolic blood pressure of 90 mm Hg or higher; a 24 h ambulatory systolic blood pressure of between 140 mm Hg and 170 mm Hg at second screening; and were on one to three antihypertensive drugs with stable doses for at least 6 weeks. Patients underwent renal angiography and were randomly assigned to undergo renal denervation or sham control. Patients, caregivers, and those assessing blood pressure were masked to randomisation assignments. The primary efficacy endpoint was blood pressure change from baseline (measured at screening visit two), based on ambulatory blood pressure measurements assessed at 6 months, as compared between treatment groups. Drug surveillance was used to assess medication adherence. The primary analysis was done in the intention-to-treat population. Safety events were assessed through 6 months as per major adverse events. This trial is registered with ClinicalTrials.gov, number NCT02439775, and follow-up is ongoing.nnnFINDINGSnBetween July 22, 2015, and June 14, 2017, 467 patients were screened and enrolled. This analysis presents results for the first 80 patients randomly assigned to renal denervation (n=38) and sham control (n=42). Office and 24 h ambulatory blood pressure decreased significantly from baseline to 6 months in the renal denervation group (mean baseline-adjusted treatment differences in 24 h systolic blood pressure -7·0 mm Hg, 95% CI -12·0 to -2·1; p=0·0059, 24 h diastolic blood pressure -4·3 mm Hg, -7·8 to -0·8; p=0.0174, office systolic blood pressure -6·6 mm Hg, -12·4 to -0·9; p=0·0250, and office diastolic blood pressure -4·2 mm Hg, -7·7 to -0·7; p=0·0190). The change in blood pressure was significantly greater at 6 months in the renal denervation group than the sham-control group for office systolic blood pressure (difference -6·8 mm Hg, 95% CI -12·5 to -1·1; p=0·0205), 24 h systolic blood pressure (difference -7·4 mm Hg, -12·5 to -2·3; p=0·0051), office diastolic blood pressure (difference -3·5 mm Hg, -7·0 to -0·0; p=0·0478), and 24 h diastolic blood pressure (difference -4·1 mm Hg, -7·8 to -0·4; p=0·0292). Evaluation of hourly changes in 24 h systolic blood pressure and diastolic blood pressure showed blood pressure reduction throughout 24 h for the renal denervation group. 3 month blood pressure reductions were not significantly different between groups. Medication adherence was about 60% and varied for individual patients throughout the study. No major adverse events were recorded in either group.nnnINTERPRETATIONnRenal denervation in the main renal arteries and branches significantly reduced blood pressure compared with sham control with no major safety events. Incomplete medication adherence was common.nnnFUNDINGnMedtronic.

One-Year Outcomes in “Real-World” Patients Treated With a Thin-Strut, Platinum-Chromium, Everolimus-Eluting Stent (from the PROMUS Element Plus US Post-Approval Study [PE-Plus PAS])

The PROMUS Element Plus US Post-Approval Study (PE-Plus PAS) was a prospective, open-label, multicenter, observational study designed to examine outcomes in everyday clinical practice in patients treated with everolimus-eluting, platinum-chromium PROMUS Element Plus stents at 52 centers in the United States. This is the first report of results from this large study. The primary end point of the PE-Plus PAS was 12-month cardiac death or myocardial infarction in the more restricted population of PLATINUM-like patients pooled from the PE-Plus PAS, PE-PROVE (PROMUS Element European post-approval study), and PLATINUM Workhorse/Small Vessel trials. Additional clinical end points were tested in the overall PE-Plus PAS patient population. Of the 2,683 patients enrolled in PE-Plus PAS, 70% were men, mean age was 64 years, 33% had diabetes, and 29% were PLATINUM-like. Among the PLATINUM-like patients, 12-month cardiac death or myocardial infarction was 1.8% (33 of 1,855) with an upper 1-sided 95% confidence interval of 2.3%, which was significantly less than the prespecified performance goal of 3.2% (pnoninferiority <0.001). In the overall PE-Plus population, 12-month target vessel failure (defined as death, MI, or revascularization related to the target vessel) was 6.7% (170 of 2,554), cardiac death was 1.4% (37 of 2,554), MI was 1.1% (28 of 2,554), and ARC-definite/probable stent thrombosis was 0.7% (19 of 2,554). A prespecified secondary end point of 12-month target vessel failure in diabetic patients demonstrated a rate of 4.2% (14 of 332) with an upper 1-sided 95% confidence interval of 6.03%, which was significantly less than the performance goal of 12.6% (pnoninferiority <0.001). In conclusion, in this large registry of unselected patients, coronary artery revascularization with the PROMUS Element Plus everolimus-eluting stent demonstrates favorable results with low 1-year clinical event rates.

Stents: Safety and Efficacy

Drug-eluting stents revolutionized the safety and efficacy of percutaneous coronary intervention and remain the backbone of percutaneous revascularization. Through iterative advances and persistent innovation stent design, vascular biology, and pharmacology, the continued expectation is that advances in design and composition will provide long-term durability and safety for the millions of patients with coronary disease globally.

Transradial approach for coronary chronic total occlusion interventions

To examine the impact of transradial access on the procedural outcomes of chronic total occlusion (CTO) percutaneous coronary interventions (PCI).