Jasvindar Singh

Use of the Instantaneous Wave-free Ratio or Fractional Flow Reserve in PCI

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<0.001 for noninferiority; hazard ratio, 0.95; 95% CI, 0.68 to 1.33; P=0.78). The risk of each component of the primary end point and of death from cardiovascular or noncardiovascular causes did not differ significantly between the groups. The number of patients who had adverse procedural symptoms and clinical signs was significantly lower in the iFR group than in the FFR group (39 patients [3.1%] vs. 385 patients [30.8%], P<0.001), and the median procedural time was significantly shorter (40.5 minutes vs. 45.0 minutes, P=0.001). Conclusions Coronary revascularization guided by iFR was noninferior to revascularization guided by FFR with respect to the risk of major adverse cardiac events at 1 year. The rate of adverse procedural signs and symptoms was lower and the procedural time was shorter with iFR than with FFR. (Funded by Philips Volcano; DEFINE‐FLAIR ClinicalTrials.gov number, NCT02053038.)

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

BACKGROUND Previous 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. METHODS SPYRAL 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. FINDINGS Between 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. INTERPRETATION Results from SPYRAL HTN-OFF MED provide biological proof of principle for the blood-pressure-lowering efficacy of renal denervation. FUNDING Medtronic.

Long-Term Outcomes With Use of Intravascular Ultrasound for the Treatment of Coronary Bifurcation Lesions

Percutaneous coronary intervention (PCI) of bifurcation lesions remains challenging with a higher risk of adverse outcomes. Whether adjunctive intravascular ultrasound (IVUS) imaging improves outcomes of PCI of bifurcation lesions remains unclear. This study sought to determine the long-term clinical outcomes associated with using IVUS for percutaneous treatment of coronary bifurcation lesions. From April 2003 through August 2010, 449 patients with 471 bifurcation lesions underwent PCI with (n = 247) and without (n = 202) the use of IVUS. Clinical outcomes (death, myocardial infarction [MI], periprocedural MI, stent thrombosis, target vessel revascularization [TVR], and target lesion revascularization [TLR]) were compared between patients undergoing PCI with and without IVUS using univariate and propensity score-adjusted analyses. Most patients (61%) presented with acute coronary syndrome and 89% of bifurcations lesions were Medina class 1,1,1. After propensity score adjustment, use of IVUS was associated with significantly lower rates of death or MI (odds ratio 0.38, 95% confidence interval 0.20 to 0.74, p = 0.005), death (odds ratio 0.40, 95% confidence interval 0.18 to 0.88, p = 0.02), MI (odds ratio 0.37, 95% confidence interval 0.14 to 0.98, p = 0.04), periprocedural MI (odds ratio 0.45, 95% confidence interval 0.20 to 0.97, p = 0.04), TVR (odds ratio 0.28, 95% confidence interval 0.14 to 0.53, p <0.0001), and TLR (odds ratio 0.27, 95% confidence interval 0.14 to 0.53, p = 0.0003) compared to no IVUS. In conclusion, IVUS-guided treatment of complex bifurcation lesions was associated with significantly lower rates of adverse cardiac events at late follow-up. Further study is warranted to evaluate the role of IVUS guidance in improving long-term outcomes after PCI of bifurcation lesions.

Endovascular brachytherapy for treatment of bilateral renal artery in-stent restenosis

Percutaneous transluminal angioplasty of renal artery stenosis is an attractive alternative to surgical therapy. However, even with endovascular stenting, the overall rate of restenosis is 21%. While brachytherapy for coronary in‐stent restenosis has proven efficacy, its use for renal artery in‐stent restenosis has not been formally evaluated. We report a case of bilateral in‐stent renal artery restenosis treated with endovascular brachytherapy. Cathet Cardiovasc Intervent 2003;59:251–254.

Risk model for estimating the 1-year risk of deferred lesion intervention following deferred revascularization after fractional flow reserve assessment

AIMS Although lesions deferred revascularization following fractional flow reserve (FFR) assessment have a low risk of adverse cardiac events, variability in risk for deferred lesion intervention (DLI) has not been previously evaluated. The aim of this study was to develop a prediction model to estimate 1-year risk of DLI for coronary lesions where revascularization was not performed following FFR assessment. METHODS AND RESULTS A prediction model for DLI was developed from a cohort of 721 patients with 882 coronary lesions where revascularization was deferred based on FFR between 10/2002 and 7/2010. Deferred lesion intervention was defined as any revascularization of a lesion previously deferred following FFR. The final DLI model was developed using stepwise Cox regression and validated using bootstrapping techniques. An algorithm was constructed to predict the 1-year risk of DLI. During a mean (±SD) follow-up period of 4.0 ± 2.3 years, 18% of lesions deferred after FFR underwent DLI; the 1-year incidence of DLI was 5.3%, while the predicted risk of DLI varied from 1 to 40%. The final Cox model included the FFR value, age, current or former smoking, history of coronary artery disease (CAD) or prior percutaneous coronary intervention, multi-vessel CAD, and serum creatinine. The c statistic for the DLI prediction model was 0.66 (95% confidence interval, CI: 0.61-0.70). CONCLUSION Patients deferred revascularization based on FFR have variation in their risk for DLI. A clinical prediction model consisting of five clinical variables and the FFR value can help predict the risk of DLI in the first year following FFR assessment.

Association of Lower Fractional Flow Reserve Values With Higher Risk of Adverse Cardiac Events for Lesions Deferred Revascularization Among Patients With Acute Coronary Syndrome

Background The safety of deferring revascularization based on fractional flow reserve (FFR) during acute coronary syndrome (ACS) is unclear. We evaluated the association of FFR and adverse cardiac events among patients with coronary lesions deferred revascularization based on FFR in the setting of ACS versus non-ACS. Methods and Results The study population (674 patients; 816 lesions) was divided into ACS (n=334) and non-ACS (n=340) groups based on the diagnosis when revascularization was deferred based on FFR values >0.80 between October 2002 and July 2010. The association and interaction between FFR and clinical outcomes was evaluated using Cox proportional hazards models within each group (mean follow-up of 4.5±2.1 years). Subsequent revascularization of a deferred lesion was classified as a deferred lesion intervention (DLI), whereas the composite of DLI or myocardial infarction (MI) attributed to a deferred lesion was designated as deferred lesion failure (DLF). In the non-ACS group, lower FFR values were not associated with any increase in adverse cardiac events. In the ACS group, every 0.01 decrease in FFR was associated with a significantly higher rate of cardiovascular death, MI, or DLI (hazard ratio [HR], 1.08; 95% confidence interval [CI], 1.03 to 1.12), MI or DLI (HR, 1.09; 95% CI: 1.04 to 1.14), DLF (HR, 1.12; 95% CI, 1.06 to 1.18), MI (HR, 1.07; 95% CI, 1.00 to 1.14), and DLI (HR, 1.12; 95% CI, 1.06 to 1.18). Conclusion Lower FFR values among ACS patients with coronary lesions deferred revascularization based on FFR are associated with a significantly higher rate of adverse cardiac events. This association was not observed in non-ACS patients.

Outcomes of Coronary Stenoses Deferred Revascularization for Borderline Versus Nonborderline Fractional Flow Reserve Values

Current evidence supports deferral of revascularization for lesions with fractional flow reserve (FFR) values >0.80. The natural history after deferral of revascularization of lesions with borderline FFR values is unknown. This study evaluated the outcomes of patients after deferred revascularization of coronary stenoses based on a borderline FFR value. We retrospectively studied 720 patients with 881 intermediate-severity coronary stenoses who underwent FFR assessment from October 2002 to July 2010 and were deferred revascularization. Patients were divided into gray zone (0.75 to 0.80), borderline (0.81 to 0.85), and nonborderline (>0.85) FFR groups. Any subsequent percutaneous coronary intervention or coronary artery bypass grafting of a deferred stenosis during follow-up was classified as a deferred lesion intervention (DLI). Patient and/or lesion characteristics and clinical outcomes were compared between the FFR groups using univariate and propensity score-adjusted inverse probability of weighting Cox proportional hazards analyses. During a mean follow-up of 4.5 ± 2.1 years, 157 deferred lesions (18%) underwent DLI by percutaneous coronary intervention (n = 117) or coronary artery bypass grafting (n = 40). No statistically significant differences were observed in clinical outcomes between the gray zone and borderline FFR groups. Lesions with a borderline FFR were associated with a significantly higher risk of DLI compared with lesions with nonborderline FFR values (hazard ratio 1.63, 95% confidence interval 1.14 to 2.33, p = 0.007). Lesions deferred revascularization because of a borderline FFR (0.81 to 0.85) were associated with a higher risk of DLI compared with lesions with a nonborderline FFR (>0.85). Further study is needed to determine the optimal management of coronary stenoses with a borderline FFR value.

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

BACKGROUND Previous 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. METHODS In 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. FINDINGS Between 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. INTERPRETATION Renal 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. FUNDING Medtronic.

Coronary subclavian steal syndrome.

Purpose of review Coronary subclavian steal syndrome (CSSS) is the reversal of blood flow in an internal mammary artery bypass graft that results in coronary ischemia. CSSS is an uncommon but treatable cause of coronary ischemia. In this review, we highlight the historical background and epidemiology of CSSS, common clinical presentations, diagnosis of CSSS and management strategies for relieving ischemia. We also present a case report to illustrate the complexity of CSSS and percutaneous management using current technology. Recent findings Most commonly, CSSS results from atherosclerotic stenosis of the subclavian artery and occurs in 2.5–4.5% of patients referred for coronary artery bypass grafting (CABG). All patients referred for CABG should have bilateral noninvasive brachial blood pressures checked to screen for the underlying subclavian stenosis. A review of 98 case reports with 128 patients demonstrated a diverse clinical presentation of CSSS, including acute myocardial infarction, unstable angina and acute systolic heart failure. Resolution of CSSS symptoms has been reported with both surgical and percutaneous revascularization. Long-term patency with either revascularization strategy is excellent. Percutaneous revascularization is largely considered the first-line therapy for CSSS and can be safely performed prior to CABG to prevent CSSS. Summary CSSS should be suspected in patients presenting with angina, heart failure or myocardial infarction after CABG. Successful amelioration of CSSS symptoms can be safely and effectively performed via percutaneous revascularization.

Long-term clinical outcomes with the use of a modified provisional jailed-balloon stenting technique for the treatment of nonleft main coronary bifurcation lesions.

To assess the long‐term clinical outcomes associated with treatment of nonleft main coronary bifurcation lesions using a modified provisional jailed‐balloon technique (JBT).