Chandan Devireddy

Transcatheter aortic valve replacement versus surgical valve replacement in intermediate-risk patients: a propensity score analysis

BACKGROUND Transcatheter aortic valve replacement (TAVR) with the SAPIEN 3 valve demonstrates good 30 day clinical outcomes in patients with severe aortic stenosis who are at intermediate risk of surgical mortality. Here we report longer-term data in intermediate-risk patients given SAPIEN 3 TAVR and compare outcomes to those of intermediate-risk patients given surgical aortic valve replacement. METHODS In the SAPIEN 3 observational study, 1077 intermediate-risk patients at 51 sites in the USA and Canada were assigned to receive TAVR with the SAPIEN 3 valve [952 [88%] via transfemoral access) between Feb 17, 2014, and Sept 3, 2014. In this population we assessed all-cause mortality and incidence of strokes, re-intervention, and aortic valve regurgitation at 1 year after implantation. Then we compared 1 year outcomes in this population with those for intermediate-risk patients treated with surgical valve replacement in the PARTNER 2A trial between Dec 23, 2011, and Nov 6, 2013, using a prespecified propensity score analysis to account for between-trial differences in baseline characteristics. The clinical events committee and echocardiographic core laboratory methods were the same for both studies. The primary endpoint was the composite of death from any cause, all strokes, and incidence of moderate or severe aortic regurgitation. We did non-inferiority (margin 7·5%) and superiority analyses in propensity score quintiles to calculate pooled weighted proportion differences for outcomes. FINDINGS At 1 year follow-up of the SAPIEN 3 observational study, 79 of 1077 patients who initiated the TAVR procedure had died (all-cause mortality 7·4%; 6·5% in the transfemoral access subgroup), and disabling strokes had occurred in 24 (2%), aortic valve re-intervention in six (1%), and moderate or severe paravalvular regurgitation in 13 (2%). In the propensity-score analysis we included 963 patients treated with SAPIEN 3 TAVR and 747 with surgical valve replacement. For the primary composite endpoint of mortality, strokes, and moderate or severe aortic regurgitation, TAVR was both non-inferior (pooled weighted proportion difference of -9·2%; 90% CI -12·4 to -6; p<0·0001) and superior (-9·2%, 95% CI -13·0 to -5·4; p<0·0001) to surgical valve replacement. INTERPRETATION TAVR with SAPIEN 3 in intermediate-risk patients with severe aortic stenosis is associated with low mortality, strokes, and regurgitation at 1 year. The propensity score analysis indicates a significant superiority for our composite outcome with TAVR compared with surgery, suggesting that TAVR might be the preferred treatment alternative in intermediate-risk patients. FUNDING None.

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

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

Comparison of transfemoral transcatheter aortic valve replacement performed in the catheterization laboratory (minimalist approach) versus hybrid operating room (standard approach): outcomes and cost analysis.

OBJECTIVES The aim of this study was to compare transfemoral transcatheter aortic valve replacement (TF TAVR) performed in a catheterization laboratory (minimalist approach [MA]) with TF TAVR performed in a hybrid operating room (standard approach [SA]). BACKGROUND A MA-TF TAVR can be performed without general anesthesia, transesophageal echocardiography, or a surgical hybrid room. The outcomes and cost of MA-TF TAVR compared with those of the SA have not been described. METHODS Patients who underwent elective, percutaneous TF TAVR using the Edwards Sapien valve (Edwards Lifesciences, Irvine, California) were studied. Baseline characteristics, outcomes, and hospital costs of MA-TF TAVR and SA-TF TAVR were compared. RESULTS A total of 142 patients were studied (MA-TF TAVR, n = 70 and SA-TF TAVR, n = 72). There were no differences in baseline comorbidities (Society of Thoracic Surgeons score, 10.6 ± 4.3 vs. 11.4 ± 5.8; p = 0.35). All procedures in the MA-TF TAVR group were successful; 1 patient was intubated. Three patients in the SA-TF TAVR group had procedure-related death. Procedure room time (150 ± 48 min vs. 218 ± 56 min, p < 0.001), total intensive care unit time (22 h vs. 28 h, p < 0.001), length of stay from procedure to discharge (3 days vs. 5 days, p < 0.001), and cost (

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

45,485 ± 14,397 vs.

Transapical and Transaortic Transcatheter Aortic Valve Replacement in the United States

55,377 ± 22,587, p < 0.001) were significantly less in the MA-TF TAVR group. Mortality at 30 days was not significantly different in the MA-TF TAVR group (0 vs. 6%, p = 0.12) and 30-day stroke/transient ischemic attack was similar (4.3% vs. 1.4%, p = 0.35). Moderate or severe paravalvular leak and device success were similar in the MA-TF TAVR and SA-TF TAVR groups (3% vs. 5.8%, p = 0.4 and 90% vs. 88%, p = 0.79, respectively) at 30 days. At a median follow-up of 435 days, there was no significant difference in survival (MA-TF TAVR, 83% vs. SA-TF TAVR, 82%; p = 0.639). CONCLUSIONS MA-TF TAVR can be performed with minimal morbidity and mortality and equivalent effectiveness compared with SA-TF TAVR. The shorter length of stay and lower resource use with MA-TF TAVR significantly lowers hospital costs.

Clinical and Angiographic Results After Hybrid Coronary Revascularization

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.

Prevalence of Resistant Hypertension and Eligibility for Catheter-Based Renal Denervation in Hypertensive Outpatients

BACKGROUND When transcatheter aortic valve replacement (TAVR) cannot be carried out through transfemoral access, alternative access TAVR is indicated. The purpose of this study was to explore inhospital and 1-year outcomes of patients undergoing alternative access TAVR through the transapical (TA) or transaortic (TAo) techniques in the United States. METHODS Clinical records of 4,953 patients undergoing TA (n = 4,085) or TAo (n = 868) TAVR from 2011 to 2014 in The Society of Thoracic Surgeons (STS)/American College of Cardiology Transcatheter Valve Therapy Registry were linked to Centers for Medicare and Medicaid Services hospital claims. Inhospital and 1-year clinical outcomes were stratified by operative risk; and the risk-adjusted association between access route and mortality, stroke, and heart failure repeat hospitalization was explored. RESULTS Mean age for all patients was 82.8 ± 6.8 years. The median STS predicted risk of mortality was significantly higher among patients undergoing TAo (8.8 versus 7.4, p < 0.001). When compared with TA, TAo was associated with an increased risk of unadjusted 30-day mortality (10.3% versus 8.8%) and 1-year mortality (30.3% versus 25.6%, p = 0.006). There were no significant differences between TAo and TA for inhospital stroke rate (2.2%), major vascular complications (0.3%), and 1-year heart failure rehospitalizations (15.7%). Examination of high-risk and inoperable subgroups showed that 1-year mortality was significantly higher for TAo patients classified as inoperable (p = 0.012). CONCLUSIONS Patients undergoing TAo TAVR are older, more likely female, and have significantly higher STS predicted risk of mortality scores than patients operated on by TA access. There were no risk-adjusted differences between TA and TAo access in mortality, stroke, or readmission rates as long as 1 year after TAVR.

A novel catheter in patients with peripheral chronic total occlusions: A single center experience†

BACKGROUND With hybrid coronary revascularization (HCR), minimally invasive left internal mammary artery (LIMA) to left anterior descending coronary artery (LAD) grafting is combined with percutaneous coronary intervention (PCI) of non-LAD vessels. The purpose of this study was to examine the short-term clinical and angiographic results in one of the largest HCR series to date. METHODS From 2003 to 2012, 300 consecutive patients (aged 64±12 years, female 31.7%, predicted risk of mortality 1.6%±2.1%) underwent HCR on an intent-to-treat basis at a single institution. After robotic or thoracoscopic LIMA harvest, off-pump LIMA to LAD grafting was performed through a 3- to 4-cm sternal-sparing, non-rib-spreading thoracotomy. PCI was utilized to treat non-LAD lesions either before, after, or concomitant with the surgical procedure. RESULTS Of the 300 patients undergoing HCR on an intent-to-treat basis, HCR was performed with surgery first in 192 patients (64.0%), PCI first in 56 (18.7%), and as a concomitant procedure in 21 (7.0%). Of the 31 patients (10.1%) who did not undergo HCR, 24 patients (8.0%) did not have PCI and thus were incompletely revascularized. For all patients, 30-day mortality, stroke, and nonfatal myocardial infarction occurred in 4 (1.3%), 3 (1.0%), and 4 (1.3%), respectively. Angiographic LIMA evaluation was performed in 248 patients and revealed a FitzGibbon A LIMA patency rate of 97.6% (242 of 248 patients). Repeat revascularization was required in 13 of 300 patients (4.3%). CONCLUSIONS Hybrid coronary revascularization represents an alternative approach for patients with multivessel coronary disease with excellent short-term outcomes. It provides a minimally invasive alternative to traditional coronary artery bypass graft surgery and may prove more durable than multivessel PCI.

Localization of culprit lesions in coronary arteries of patients with ST-segment elevation myocardial infarctions: Relation to bifurcations and curvatures

BACKGROUND Studies of endovascular renal denervation (RDN) have demonstrated significant blood pressure reduction in eligible patients with resistant hypertension. These trials have used stringent inclusion and exclusion criteria in patient enrollment, potentially selecting for a small subset of patients with resistant hypertension. In this study, we examined the changes in estimated prevalence of resistant hypertension when using increasingly stringent definitions of resistant hypertension in a fixed population and assessed the generalizability of RDN when applying study criteria to a community-based hypertensive population. METHODS A retrospective chart review was done of hypertensive outpatients. Four increasingly stringent interpretations of the American Heart Association definition of resistant hypertension were used to calculate prevalence estimates. Patients eligible for RDN were identified using criteria from SYMPLICITY HTN-3. Demographic and clinical characteristics were compared. RESULTS We identified 1,756 hypertensive outpatients; 55.0% were male, 53.9% were white, and subjects had a mean age of 66.6 ± 12.5 years and a body mass index (BMI) of 30.1 ± 10.7 kg/m(2). Only 14 (0.8%) were eligible for RDN. Among these patients, 10 (71.4%) were female and all were black, with a mean age of 69.9 ± 8.8 and BMI of 35.7 ± 6.6. Congestive heart failure was more common in patients eligible for RDN. CONCLUSIONS Patients eligible for RDN based on published studies represent an exceedingly small proportion of the total hypertensive population. Further studies are necessary to determine if the benefits of RDN can be generalized to a broader range of hypertensive patients than those included in previous trials.

Safety of catheter‐directed thrombolysis for massive and submassive pulmonary embolism: Results of a multicenter registry and meta‐analysis

Objectives and Background: Recanalization of a chronic total occlusion (CTO) is technically challenging with less than optimum results in arterial disease. Crosser® is a novel technology that utilizes high frequency (20 KHz) vibration energy to fragment occlusive fibrous atherosclerotic plaque and helps in traversing the occluded vessel. We report a single center experience with this catheter as the primary device in peripheral chronic total occlusions. Methods: The catheter was used as the primary device in 25 consecutive patients with peripheral CTOs. The peripheral CTOs in this study are defined as 100% occluded vessels involving any segment of the iliac artery or below the inguinal ligament down to the trifurcation vessels which have been occluded for greater than 3 months judged by patients history of longstanding symptoms with no worsening in the past 3 months. Procedural success was defined by the ability of the device to facilitate guide wire crossing of the occlusion. All angiograms were evaluated by two operators. Data on demographics, angiographic variables, and patient complications was collected. Results: The device was used in 25 consecutive patients and 27 CTO lesions were treated. Critical limb ischemia and claudication were the indications in 32 and 68% of the patients, respectively. Average lesion length was 117 mm (range 10–300 mm). Superficial femoral artery was the most common lesion site (n = 20, 74%). Crosser‐assisted guide wire recanalization was achieved in 11(41%) lesions while the final overall procedure success rate with any device was 63% (n = 17). Perforation occurred in five lesions with one directly attributable to this device. Conclusions: In this single center observational review, the Crosser device in peripheral CTO lesions had a procedural success of 41%.