Feasibility and Validity of Computed Tomography-Derived Fractional Flow Reserve in Patients With Severe Aortic Stenosis: The CAST-FFR Study.

BACKGROUND: Coronary artery disease is common in patients with severe aortic stenosis. Computed tomography-derived fractional flow reserve (CT-FFR) is a clinically used modality for assessing coronary artery disease, however, its use has not been validated in patients with severe aortic stenosis. This study assesses the safety, feasibility, and validity of CT-FFR in patients with severe aortic stenosis. METHODS: Prospectively recruited patients underwent standard-protocol invasive FFR and coronary CT angiography (CTA). CTA images were analyzed by central core laboratory (HeartFlow, Inc) for independent evaluation of CT-FFR. CT-FFR data were compared with FFR (ischemia defined as FFR ≤0.80). RESULTS: Forty-two patients (68 vessels) underwent FFR and CTA; 39 patients (92.3%) and 60 vessels (88.2%) had interpretable CTA enabling CT-FFR computation. Mean age was 76.2±6.7 years (71.8% male). No patients incurred complications relating to premedication, CTA, or FFR protocol. Mean FFR and CT-FFR were 0.83±0.10 and 0.77±0.14, respectively. CT calcium score was 1373.3±1392.9 Agatston units. On per vessel analysis, there was positive correlation between FFR and CT-FFR (Pearson correlation coefficient, R=0.64, P<0.0001). Sensitivity, specificity, positive predictive value, and negative predictive values were 73.9%, 78.4%, 68.0%, and 82.9%, respectively, with 76.7% diagnostic accuracy. The area under the receiver-operating characteristic curve for CT-FFR was 0.83 (0.72-0.93, P<0.0001), which was higher than that of CTA and quantitative coronary angiography (P=0.01 and P<0.001, respectively). Bland-Altman plot showed mean bias between FFR and CT-FFR as 0.059±0.110. On per patient analysis, the sensitivity, specificity, positive predictive, and negative predictive values were 76.5%, 77.3%, 72.2%, and 81.0% with 76.9% diagnostic accuracy. The per patient area under the receiver-operating characteristic curve analysis was 0.81 (0.67-0.95, P<0.0001). CONCLUSIONS: CT-FFR is safe and feasible in patients with severe aortic stenosis. Our data suggests that the diagnostic accuracy of CT-FFR in this cohort potentially enables its use in clinical practice and provides the foundation for future research into the use of CT-FFR for coronary evaluation pre-aortic valve replacement.

Angiographic Functional Scoring of Coronary Artery Disease Predicts Mortality in Patients With Severe Aortic Stenosis Undergoing TAVR.

BACKGROUND/PURPOSE: Coronary artery disease (CAD) is common in patients undergoing transcatheter aortic valve replacement (TAVR), although its prognostic significance is questionable. Significant CAD stratified using SYNTAX score (SS) has been associated with greater mortality, yet it is unknown whether the functional impact of CAD also impacts outcomes in this cohort. DILEMMA score (DS) is a validated angiographic functional scoring tool that correlates with fractional flow reserve and instantaneous wave-free ratio. This study sought to assess the functional impact of CAD on outcomes in patients undergoing TAVR for severe aortic stenosis (AS). METHODS/MATERIALS: 229 patients were included in this analysis. Patients underwent angiographic DS and SS and were classified using predefined values. The primary endpoint was one-year all-cause mortality, with secondary endpoints of 30-day major adverse cardiac and cerebrovascular events (MACCE). RESULTS: The mean age was 83.9 ± 0.5 years (55.0% female), with 11.8% all-cause mortality. CAD defined by ≥30% stenosis in any vessel was not associated with adverse outcomes (HR = 1.08, p = 0.84). However, the risk of one-year mortality was greater in patients with either SS > 9 (20.8% vs. 9.4%, HR 2.34, p = 0.03) or DS > 2 (18.4% vs. 8.5%, HR = 2.28, p = 0.03). Both scoring systems were also associated with 30-day MACCE (both p < 0.05). After multivariate adjustment, independent predictors of one-year mortality were DS > 2 (HR = 2.29, p = 0.04), left ventricular ejection fraction <50% (HR 2.66, p = 0.04) and COPD (HR 2.43, p = 0.04). CONCLUSION: Our results demonstrate that angiographic functional scoring is independently predictive of both 12-month mortality and 30-day MACCE following TAVR.

Acute Effects of Transcatheter Aortic Valve Replacement on Central Aortic Hemodynamics in Patients With Severe Aortic Stenosis.

Severe aortic stenosis induces abnormalities in central aortic pressure, with consequent impaired organ and tissue perfusion. Relief of aortic stenosis by transcatheter aortic valve replacement (TAVR) is associated with both a short- and long-term hypertensive response. Counterintuitively, patients who are long-term normotensive post-TAVR have a worsened prognosis compared with patients with hypertension, yet the underlying mechanisms are not understood. We investigated immediate changes in invasively measured left ventricular and central aortic pressure post-TAVR in patients with severe aortic stenosis using aortic reservoir pressure, wave intensity analysis, and indices of aortic function. Fifty-four patients (mean age 83.6±6.2 years, 50.0% female) undergoing TAVR were included. We performed reservoir pressure and wave intensity analysis on invasively acquired pressure waveforms from the ascending aorta and left ventricle immediately pre- and post-TAVR. Following TAVR, there were increases in systolic, diastolic, mean, and pulse aortic pressures (all P<0.05). Post-TAVR reservoir pressure was unchanged (54.5±12.4 versus 56.6±14.0 mm Hg, P=0.30) whereas excess pressure increased 47% (29.0±10.9 versus 42.6±15.5 mm Hg, P<0.001). Wave intensity analysis (arbitrary units, au) demonstrated increased forward compression wave (64.9±35.5 versus 124.4±58.9, ×103 au, P<0.001), backward compression wave (11.6±5.5 versus 14.4±6.9, ×103 au, P=0.01) and forward expansion wave energies (43.2±27.3 versus 82.8±53.1, ×103 au, P<0.001). Subendocardial viability ratio improved with aortic function effectively unchanged post-TAVR. Increased central aortic pressure following TAVR relates to increased transmitted power and energy to the proximal aorta with increased excess pressure but unchanged reservoir pressure. These changes provide a potential mechanism for the improved prognosis associated with relative hypertension post-TAVR.

The role of Glucagon-Like Peptide 1 Loading on periprocedural myocardial infarction During elective PCI (GOLD-PCI study): A randomized, placebo-controlled trial.

BACKGROUND: The incretin hormone glucagon-like peptide 1 (GLP-1) has been shown to protect against lethal ischemia-reperfusion injury in animal models and against nonlethal ischemia reperfusion injury in humans. Furthermore, GLP-1 receptor agonists have been shown to reduce major adverse cardiovascular and cerebrovascular events (MACCE) in large-scale studies. We sought to investigate whether GLP-1 reduced percutaneous coronary intervention (PCI)-associated myocardial infarction (PMI) during elective PCI. METHODS: The study was a randomized, double-blind controlled trial in which patients undergoing elective PCI received an intravenous infusion of either GLP-1 at 1.2 pmol/kg/min or matched 0.9% saline placebo before and during the procedure. Randomization was performed in 1:1 fashion, with stratification for diabetes mellitus. Six-hour cardiac troponin I (cTnI) was measured with a primary end point of PMI defined as rise ≫×5 upper limit of normal (280 ng/L). Secondary end points included cTnI rise and MACCE at 12 months. RESULTS: A total of 192 patients were randomized with 152 (79%) male and a mean age of 68.1 ±â€¯8.9 years. No significant differences in patient demographics were noted between the groups. There was no difference in the rate of PMI between GLP-1 and placebo (9 [9.8%] vs 8 [8.3%], P = 1.0) or in the secondary end points of difference in median cTnI between groups (9.5 [0-88.5] vs 20 [0-58.5] ng/L, P = .25) and MACCE at 12 months (7 [7.3%] vs 9 [9.4%], P = .61). CONCLUSIONS: In this randomized, placebo-controlled trial, GLP-1 did not reduce the low incidence of PMI or abrogate biomarker rise during elective PCI, nor did it influence the 12-month MACCE rate which also remained low. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov Number: NCT02127996https://clinicaltrials.gov/ct2/show/NCT02127996.

Periprocedural Myocardial Injury Predicts Short- and Long-Term Mortality in Patients Undergoing Transcatheter Aortic Valve Replacement.

BACKGROUND: The aim was to assess whether periprocedural myocardial injury (PPMI) predicts outcomes in patients undergoing transcatheter aortic valve replacement (TAVR). PPMI is a strong predictor of outcomes following coronary intervention, but its impact in the context of TAVR remains unclear. We performed a systematic review and meta-analysis to ascertain the association between PPMI and short- or long-term outcomes. METHODS AND RESULTS: Electronic searches identified studies reporting PPMI following TAVR. Primary end point was 30-day all-cause mortality, with secondary end points, including 1-year all-cause mortality, neurological events, post-TAVR pacemaker implantation, and aortic regurgitation. Analyses were performed using random effects modeling and reported as summary odds ratio (OR) with 95% CI. Nine studies comprising 3442 patients (mean age 81.0±6.6 years, 51.2% female) were included. PPMI occurred in 25.5% of patients following TAVR. The pooled all-cause mortality at 30-days and 1-year was 5.2% and 18.6%, respectively. The occurrence of PPMI following TAVR was associated with significantly increased risk of both 30-day (OR, 4.23; CI, 1.95-9.19; P<0.001) and 1-year all-cause mortality (OR, 1.77; CI, 1.05-2.99; P<0.001). Similarly, PPMI was associated with post-TAVR neurological events (OR, 2.72; CI, 1.69-4.37; P<0.001) and post-TAVR permanent pacing (OR, 1.43; CI, 1.02-2.00; P=0.04) but not with a statistically significant increase in aortic regurgitation post-TAVR (OR, 1.39; CI, 0.93-2.08; P=0.11). CONCLUSIONS: PPMI is common following TAVR and is strongly associated with 30-day and 1-year mortality. Detection of PPMI has potential to identify TAVR patients at highest risk of subsequent adverse events.

Diagnostic accuracy of ASLA score (a novel CT angiographic index) and aggregate plaque volume in the assessment of functional significance of coronary stenosis.

BACKGROUND: Visual assessment of diameter-stenosis on Computed Tomography Coronary Angiography (CTCA) lacks specificity to determine functional significance of coronary artery stenosis. Percent-aggregate plaque volume (%APV) and ASLA score, which incorporates Area of Stenosis, Lesion length, and area of myocardium subtended estimated by APPROACH score (Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease) have been described to predict lesion specific ischaemia in focal lesions with intermediate stenosis. METHODS AND RESULTS: Included were 81 patients (mean age 64.7 ±â€¯9 years, 62% male; 94 vessels) who underwent 320- detector-row CTCA, invasive coronary angiography and fractional-flow-reserve (FFR). We examined vessels with wide range of diameter stenosis (mid to severe) and with multiple lesions. Invasive FFR of ≤0.8 was considered functionally significant. The first 54 patients (62 vessels) formed the derivation cohort. ASLA score was the best predictor of FFR ≤ 0.8 (AUC 0.83, p < 0.001) compared to %APV (0.72), CT >50% (0.76), APPROACH score (0.79), area-stenosis (0.73), diameter-stenosis (0.74), minimum-luminal-diameter (0.74), minimal-luminal-area (0.72), and lesion-length (0.67). ASLA score and not %APV, provided incremental predictive value when added to CT > 50 [(NRI 0.71, p = 0.005) vs. (NRI 0.01, p = 0.96)]. In the validation cohort of 27 patients (32 vessels), the ASLA score (AUC 0.85) was again a better predictor of FFR ≤ 0.8 compared to %APV (0.71), CT > 50% (0.66) and other CT indices. The AUC of ASLA score was superior to CTCA>50% (p = 0.001). CONCLUSION: ASLA score is a novel predictor of functional significance of coronary stenosis and adds incremental predictive value to CT > 50 but %APV did not.

Subclinical Leaflet Thrombosis in Transcatheter Aortic Valve Replacement Detected by Multidetector Computed Tomography　- A Review of Current Evidence.

Subclinical leaflet thrombosis (SLT) following transcatheter aortic valve replacement (TAVR) has been increasingly recognized. SLT has the hallmark features of hypo-attenuated leaflet thickening (HALT) on multidetector computed tomography (MDCT), which may result in hypoattenuation affecting motion (HAM). The actual prevalence of this condition is uncertain, with limited observational registries. SLT has caught the attention of the cardiovascular community because of concerns regarding its clinical sequelae, specifically the potential increased incidence of cerebrovascular events. There are available, albeit sparse, data to suggest that when left untreated, SLT may lead to valve deterioration with potential hemodynamic compromise and potentially clinically overt prostheses thrombosis. Some clinicians have opted to treat patients with SLT with anticoagulation. Although anticoagulation may be a rational treatment option, little data exist on the safety and efficacy of this treatment. This is particularly important considering TAVR patients also have higher bleeding risk than the standard population. In this review, we aim to summarize the current evidence on SLT, explore its pathophysiological mechanism, discuss the current treatment options and future trials that may clarify the optimal antithrombotic strategies of SLT.

Novel bioabsorbable polymer and polymer-free metallic drug-eluting stents.

The introduction of drug-eluting stents (DES) significantly reduced angiographic restenosis and the clinical need for revascularization following percutaneous coronary intervention. However, concerns remain regarding the long-term safety and efficacy of DES. The use of durable polymers for drug elution that have limited biocompatibility is thought to contribute toward DES failure, by promoting an adverse local inflammatory response and vascular toxicity. Biodegradable polymer and polymer-free metallic stents represent two novel technological solutions to this challenging clinical problem. This review summarizes the available clinical evidence supporting the use of either biodegradable polymer or polymer-free DES platforms.

Bioprosthetic aortic valve leaflet thrombosis detected by multidetector computed tomography is associated with adverse cerebrovascular events: a meta-analysis of observational studies.

AIMS: Leaflet thrombosis (LT) has become increasingly recognised following transcatheter and surgical aortic bioprosthetic valve (ABV) replacement and can be reliably identified by multidetector computed tomography (MDCT). However, it is an ongoing debate whether MDCT-defined LT is associated with adverse cerebrovascular outcomes. We sought to perform a systematic review and meta-analysis in order to assess the incidence and clinical outcomes associated with MDCT-defined leaflet thrombosis following (ABV) replacement. METHODS AND RESULTS: Electronic databases were searched for studies that performed mandatory MDCT imaging following ABV replacement. The primary endpoint was the incidence of cerebrovascular events, defined as a composite of stroke or transient ischaemic attack (TIA). Secondary endpoints included major adverse cerebrovascular and cardiovascular events (MACCE), stroke, TIA, death or myocardial infarction. In total, six studies met the inclusion criteria with 11.6% (198/1,704) of patients having MDCT-defined LT. The prevalence of LT following transcatheter and surgical ABV replacement was 13.2% and 3.6%, respectively. Cerebrovascular events were significantly increased in patients with LT (odds ratio [OR] 3.38, 95% CI: 1.78-6.41, p<0.001). The risk of MACCE (OR 2.10, 95% CI: 1.21-3.64, p<0.001) and TIA (OR 5.86, 95% CI: 2.05-16.75, p<0.001) was also increased in patients with LT, although there were no differences in the incidence of stroke (OR 2.43, 95% CI: 1.00-5.93, p=0.05), death (OR 0.92, 95% CI: 0.42-2.03, p=0.84) or myocardial infarction (OR 1.72, 95% CI: 0.34-9.78, p=0.54) between groups. CONCLUSIONS: MDCT-defined LT following ABV replacement is associated with a significantly increased risk of adverse cerebrovascular events. Further prospective studies are required to ascertain whether LT can be prevented or treated with pharmacological strategies.

Effect of aorto-ventricular angulation on procedural success in transcatheter aortic valve replacements with the Lotus Valve system.

OBJECTIVE: To determine the effect of aorto-ventricular angulation (AA) on procedural success with the Lotus Valve system. BACKGROUND: AA, the angulation of the aortic valve basal plane, may affect the deployment of transcatheter aortic valve replacements (TAVRs). The Lotus Valve system is fully repositionable and delivered on a pre-shaped catheter which may alter the impact of AA on its deployment. The effect of AA on procedural and clinical outcomes with the Lotus valve is unreported. METHODS: Consecutive patients who underwent transfemoral TAVR with the Lotus Valve system were analyzed. AA was determined on pre-procedural multi-detector computed tomography imaging. Device success, procedural characteristics, and clinical events were assessed according to Valve Academic Research Consortium-2 (VARC2) definitions. RESULTS: One hundred sixty-five patients were analyzed (48% male, mean age 84 years). The mean AA was 47.8 degrees. Patients were, therefore, divided into low AA (AA < 48°) or high AA (AA ≥ 48°). Baseline characteristics were similar in both cohorts. Device success and procedural outcomes were also similar including procedure time, contrast dose, and need to reposition. There was no difference in degree of moderate or greater para-valvular regurgitation (PVR) (0% vs. 3%, P = 0.09). Clinical outcomes of death, stroke, myocardial infarction, and other major VARC2 endpoints were similar. CONCLUSION: AA did not affect device success or clinical outcome with the Lotus Valve system. The Lotus' unique design features may have mitigated the impact of AA by improving the accuracy, ease of valve positioning, and reducing PVR.

Alcohol Septal Ablation for Hypertrophic Obstructive Cardiomyopathy: A 16-Year Australian Single Centre Experience.

BACKGROUND: Alcohol septal ablation (ASA), is a well-established treatment for symptomatic hypertrophic obstructive cardiomyopathy (HOCM). We report the acute, short and long-term clinical and echocardiographic outcomes of our experience in a single Australian centre over 16 years. METHODS: We retrospectively analysed consecutive patients presenting to our centre for ASA between March 2000 and July 2016. Local databases were interrogated along with direct patient or physician contact occurred where required. RESULTS: Alcohol septal ablation was performed in 80 patients with symptomatic, medication refractory HOCM (mean age 61±15 years; range 22-84 years; 50% male). All patients had transthoracic echocardiography prior to the procedure, within 48hours of the procedure, 6 weeks, 6 months, 1 year and yearly thereafter to a median follow-up of 80±40months. At baseline, mean resting and provoked LVOT gradients were 80±49mmHg and 97±40mmHg respectively. Compared with baseline, ASA led to a reduction in resting LVOT gradients at all time points, particularly at 2 days-52±41mmHg, p<0.001; 12 months-29±34mmHg, p<0.001; and last follow-up 12±21mmHg, p<0.001. Provoked LVOT gradients were also reduced at 2 days-64±44mmHg and last follow-up of 19±29mmHg, p<0.001. Compared to baseline (19.8±4.2mm), ASA was associated with a reduction in interventricular septal (IVS) thickness at all time intervals with last echocardiographic follow-up at 80 months being 16.0±4.9mm, (

Simultaneous transcatheter aortic valve implantation and drive-by endovascular aortic aneurysm repair: a case of lotus valve retrieved and replaced due to an undersized valve after an endovascular aneurysm repair.

A 79-year-old man with stable chronic obstructive pulmonary disease was found to have an abdominal aortic aneurysm and worsening dyspnoea. Echocardiography demonstrated critical aortic stenosis. Simultaneous endovascular aneurysm repair (EVAR) and transcatheter aortic valve replacement (TAVR) was recommended due to high surgical risk. Procedural strategy was to perform balloon valvuloplasty (BAV), followed by EVAR then TAVR. The initial 25 mm Lotus valve adopted a barrel shape suggestive of an undersized valve and was thus replaced with a 27 mm valve. Post procedural echo revealed no regurgitation. We report here for the first time a successful simultaneous TAVR/EVAR using the fully retrievable Lotus Valve.

Intravascular ultrasound guidance improves clinical outcomes during implantation of both first- and second-generation drug-eluting stents: a meta-analysis.

AIMS: Our aim was to assess whether intravascular ultrasound (IVUS) improves clinical outcomes during implantation of first- and second-generation drug-eluting stents (DES). IVUS guidance is associated with improved clinical outcomes during DES implantation, but it is unknown whether this benefit is limited to either first- or second-generation devices. METHODS AND RESULTS: MEDLINE, EMBASE and PubMed were searched for studies comparing outcomes between IVUS- and angiography-guided PCI. Among 909 potentially relevant studies, 15 trials met the inclusion criteria. The primary endpoint was MACE, defined as death, myocardial infarction, target vessel/lesion revascularisation (TVR/TLR) or stent thrombosis (ST). Summary estimates were obtained using Peto modelling. In total, 9,313 patients from six randomised trials and nine observational studies were included. First-generation DES were implanted in 6,156 patients (3,064 IVUS-guided and 3,092 angiography-guided) and second-generation in 3,157 patients (1,528 IVUS-guided and 1,629 angiography-guided). IVUS guidance was associated with a significant reduction in MACE (odds ratio [OR] 0.73, 95% CI: 0.64-0.85, p<0.001), across both first- (OR 0.79, 95% CI: 0.67-0.92, p=0.01) and second-generation DES (0.57, 95% CI: 0.43-0.77, p<0.001). For second-generation DES, IVUS guidance was associated with significantly lower rates of cardiac death (OR 0.33, 95% CI: 0.14-0.78, p=0.02), TVR (OR 0.47, 95% CI: 0.28-0.79, p=0.006), TLR (OR 0.61, 95% CI: 0.42-0.90, p=0.01) and ST (OR 0.31, 95% CI: 0.12-0.78, p=0.02). Cumulative meta-analysis highlighted progressive temporal benefit towards IVUS-guided PCI to reduce MACE (OR 0.60, 95% CI: 0.48-0.75, p<0.001). CONCLUSIONS: IVUS guidance is associated with a significant reduction in MACE during implantation of both first- and second-generation DES platforms. These data support the use of IVUS guidance in contemporary revascularisation procedures using second-generation DES.

Persistent type III cavity-spilling coronary perforation due to covered stent malapposition.

Coronary perforations are a rare but potentially catastrophic complication of percutaneous coronary intervention. We report a rare case of a large cavity-spilling perforation from the left anterior descending coronary artery into the left ventricle, which was successfully treated with a covered stent. However, repeating angiography 1 week later demonstrated persistence of the perforation due to stent malapposition.

Glucagon-like peptide-1 protects against ischemic left ventricular dysfunction during hyperglycemia in patients with coronary artery disease and type 2 diabetes mellitus.

BACKGROUND: Enhancement of myocardial glucose uptake may reduce fatty acid oxidation and improve tolerance to ischemia. Hyperglycemia, in association with hyperinsulinemia, stimulates this metabolic change but may have deleterious effects on left ventricular (LV) function. The incretin hormone, glucagon-like peptide-1 (GLP-1), also has favorable cardiovascular effects, and has emerged as an alternative method of altering myocardial substrate utilization. In patients with coronary artery disease (CAD), we investigated: (1) the effect of a hyperinsulinemic hyperglycemic clamp (HHC) on myocardial performance during dobutamine stress echocardiography (DSE), and (2) whether an infusion of GLP-1(7-36) at the time of HHC protects against ischemic LV dysfunction during DSE in patients with type 2 diabetes mellitus (T2DM). METHODS: In study 1, twelve patients underwent two DSEs with tissue Doppler imaging (TDI)-one during the steady-state phase of a HHC. In study 2, ten patients with T2DM underwent two DSEs with TDI during the steady-state phase of a HHC. GLP-1(7-36) was infused intravenously at 1.2 pmol/kg/min during one of the scans. In both studies, global LV function was assessed by ejection fraction and mitral annular systolic velocity, and regional wall LV function was assessed using peak systolic velocity, strain and strain rate from 12 paired non-apical segments. RESULTS: In study 1, the HHC (compared with control) increased glucose (13.0 ± 1.9 versus 4.8 ± 0.5 mmol/l, p < 0.0001) and insulin (1,212 ± 514 versus 114 ± 47 pmol/l, p = 0.01) concentrations, and reduced FFA levels (249 ± 175 versus 1,001 ± 333 µmol/l, p < 0.0001), but had no net effect on either global or regional LV function. In study 2, GLP-1 enhanced both global (ejection fraction, 77.5 ± 5.0 versus 71.3 ± 4.3%, p = 0.004) and regional (peak systolic strain -18.1 ± 6.6 versus -15.5 ± 5.4%, p < 0.0001) myocardial performance at peak stress and at 30 min recovery. These effects were predominantly driven by a reduction in contractile dysfunction in regions subject to demand ischemia. CONCLUSIONS: In patients with CAD, hyperinsulinemic hyperglycemia has a neutral effect on LV function during DSE. However, GLP-1 at the time of hyperglycemia improves myocardial tolerance to demand ischemia in patients with T2DM. TRIAL REGISTRATION: http://www.isrctn.org . Unique identifier ISRCTN69686930.

Institutional Switch from Transfemoral to Transradial Vascular Access for Percutaneous Coronary Intervention was Associated with a Reduction in Bleeding Events: A Singlecenter Experience of >10,000 Consecutive Cases.

BACKGROUND: Transradial (TR) access for percutaneous coronary intervention (PCI) reduces bleeding compared with transfemoral (TF) access, and may reduce mortality in specific patient subsets. However, switching from TF to TR access is associated with a learning curve and it is unclear whether benefits observed in randomized trials translate into practice. We sought to characterize the trends in bleeding and mortality rates at our institution, as we changed from being a TF to predominantly TR center over a 5-year period. METHODS AND RESULTS: 10,213 consecutive patients presenting for PCI were included (mean age 65.0 ± 11.6 years, 76.1% male, 48.0% PCI for acute coronary syndrome) over 5 years at a single center with PCI volume >2,000 cases per annum. Patients were stratified by initial arterial access site (TR or TF) and outcome measures included temporal trends in TR procedural failure, 30-day bleeding complications and all-cause 1-year mortality. TR procedural failure fell to a consistently low rate within 1 year (11.8% in 2008 to 2.9% in 2009, P < 0.001). As TR volume increased, the annual 30-day bleeding rate fell (1.64% in 2008 to 0.68% in 2012, P = 0.006). TR access predicted reduced 30-day bleeding (OR 0.17 [95%CI 0.07-0.38], P < 0.001), but was not a predictor of 1-year survival (HR 0.78 [95%CI 0.58-1.05], P = 0.10). CONCLUSION: Successful transition from TF to TR PCI at our institution was rapid and associated with a reduction in 30-day bleeding. These data should encourage other centers considering the adoption of TR access.

Interpretation of fractional flow reserve in ST-elevation myocardial infarction culprit lesions.

BACKGROUND: Pressure wire assessment of the infarct-related artery (IRA) in ST-elevation myocardial infarction (STEMI) is not recommended until microcirculatory dysfunction recovers. OBJECTIVE: The objective of this study was to assess serial fractional flow reserve (FFR) and the index of microcirculatory resistance (IMR) in the IRA of STEMI patients to better understand and interpret FFR during primary percutaneous coronary intervention (PPCI). METHODS: Forty-one patients undergoing PPCI for STEMI were studied with a pressure wire at baseline after thrombectomy and after stenting. RESULTS: The majority of STEMI culprit lesions in the IRA were haemodynamically significant (mean FFR pre-PPCI: 0.54±0.20); only 4/41 culprit lesions had FFR greater than 0.80. The FFR of the culprit lesion and the initial IMR were correlated (r=0.45, P=0.004). Patients with a normal initial IMR of less than 25 exhibited lower culprit lesion FFR values (0.47±0.20 vs. 0.60±0.18, P=0.03) despite milder angiographic stenoses [angiographic stenoses (%): 80.4±10.4 vs. 86.6±8.0, P=0.03] but showed a reduction in the IMR during PPCI (pre-PPCI: 16.9±5.7 vs. post-PPCI: 32.2±22.6, P=0.009). CONCLUSION: STEMI culprit lesions are haemodynamically significant. A subset of STEMI IRAs has initially preserved microcirculatory function; thus, the culprit stenosis may feasibly be assessed through FFR.

Serial assessment of the index of microcirculatory resistance during primary percutaneous coronary intervention comparing manual aspiration catheter thrombectomy with balloon angioplasty (IMPACT study): a randomised controlled pilot study.

OBJECTIVE: Utilising a novel study design, we evaluated serial measurements of the index of microcirculatory resistance (IMR) in patients undergoing primary percutaneous coronary intervention (PPCI) for ST-segment elevation myocardial infarction (STEMI) to assess the impact of device therapy on microvascular function, and determine what proportion of microvascular injury is related to the PPCI procedure, and what is an inevitable consequence of STEMI. DESIGN: 41 patients undergoing PPCI for STEMI were randomised to balloon angioplasty (BA, n=20) or manual thrombectomy (MT, n=21) prior to stenting. Serial IMR measurements, corrected for collaterals, were recorded at baseline and at each stage of the procedure. Microvascular obstruction (MVO) and infarct size at 24 h and 3 months were measured by troponin and cardiac MRI (CMR). RESULTS: IMR did not change significantly following PPCI, but patients with lower IMR values (<32, n=30) at baseline had a significant increase in IMR following PPCI (baseline: 21.2±7.9 vs post-stent: 33.0±23.7, p=0.01) attributable to prestent IRA instrumentation (baseline: 21.7±8.0 vs post-BA or MT: 36.9±25.9, p=0.006). Post-stent IMR correlated with early MVO on CMR (p=0.01). There was no significant difference in post-stent IMR, presence of early MVO or final infarct size between patients with BA and patients treated with MT. CONCLUSIONS: Patients with STEMI and less microcirculatory dysfunction may be susceptible to acute iatrogenic microcirculatory injury from prestent coronary devices. MT did not appear to be superior to BA in maintaining microcirculatory integrity when the guide wire partially restores IRA flow during PPCI. TRIAL REGISTRATION NUMBER: ISRCTN31767278.

Pre-treatment with glucagon-like Peptide-1 protects against ischemic left ventricular dysfunction and stunning without a detected difference in myocardial substrate utilization.

OBJECTIVES: This study sought to determine whether pre-treatment with intravenous glucagon-like peptide-1 (GLP-1)(7-36) amide could alter myocardial glucose use and protect the heart against ischemic left ventricular (LV) dysfunction during percutaneous coronary intervention. BACKGROUND: GLP-1 has been shown to have favorable cardioprotective effects, but its mechanisms of action remain unclear. METHODS: Twenty patients with preserved LV function and single-vessel left anterior descending coronary artery disease undergoing elective percutaneous coronary intervention were studied. A conductance catheter was placed into the LV, and pressure-volume loops were recorded at baseline, during 1-min low-pressure balloon occlusion (BO), and at 30-min recovery. Patients were randomized to receive an infusion of either GLP-1(7-36) amide at 1.2 pmol/kg/min or saline immediately after baseline measurements. Simultaneous coronary artery and coronary sinus blood sampling was performed at baseline and after BO to assess transmyocardial glucose concentration gradients. RESULTS: BO caused both ischemic LV dysfunction and stunning in the control group but not in the GLP-1 group. Compared with control subjects, the GLP-1 group had a smaller reduction in LV performance during BO (delta dP/dTmax, -4.3 vs. -19.0%, p = 0.02; delta stroke volume, -7.8 vs. -26.4%, p = 0.05), and improved LV performance at 30-min recovery. There was no difference in transmyocardial glucose concentration gradients between the 2 groups. CONCLUSIONS: Pre-treatment with GLP-1(7-36) amide protects the heart against ischemic LV dysfunction and improves the recovery of function during reperfusion. This occurs without a detected change in myocardial glucose extraction and may indicate a mechanism of action independent of an effect on cardiac substrate use. (Effect of Glucgon-Like-Peptide-1 [GLP-1] on Left Ventricular Function During Percutaneous Coronary Intervention [PCI]; ISRCTN77442023).