Disturbed Lipid Metabolism in Diabetic Patients with Manifest Coronary Artery Disease Is Associated with Enhanced Inflammation.

BACKGROUND: Diabetic vasculopathy plays an important role in the pathophysiology of coronary artery disease (CAD) with oxidative stress as a strong mediator. This study aims to elucidate the underlying pathomechanisms of diabetic cardiac vasculopathy leading to coronary disease with an emphasis on the role of oxidative stress. Therefore, novel insights into antioxidant pathways might contribute to new strategies in the treatment and prevention of diabetic CAD. METHODS: In 20 patients with insulin-dependent or non-insulin dependent diabetes mellitus (IDDM/NIDDM) and 39 non-diabetic (CTR) patients, myocardial markers of oxidative stress, vasoactive proteins, endothelial nitric oxide synthase (eNOS), activated phosphorylated eNOS (p-eNOS), and antioxidant enzymes, e.g., tetrahydrobiopterin generating dihydrofolate reductase (DHFR), heme oxygenase (HO-1), as well as serum markers of inflammation, e.g., E-selectin, interleukin-6 (IL-6), and lipid metabolism, e.g., high- and low-density lipoptrotein (HDL- and LDL-cholesterol) were determined in specimens of right atrial tissue and in blood samples from type 2 diabetic and non-diabetic patients undergoing coronary artery bypass graft (CABG) surgery. RESULTS: IDDM/NIDDM increased markers of inflammation (e.g., E-selectin, p = 0.005 and IL-6, p = 0.051), decreased the phosphorylated myocardial p-eNOS (p = 0.032), upregulated the myocardial stress response protein HO-1 (p = 0.018), and enhanced the serum LDL-/HDL-cholesterol ratio (p = 0.019). However, the oxidative stress markers in the myocardium and the expression of vasoactive proteins (eNOS, DHFR) showed only marginal adverse changes in patients with IDDM/NIDDM. CONCLUSION: Dyslipidemia and myocardial inflammation seem to be the major determinants of diabetic CAD complications. Dysregulation in pro-oxidative enzymes might be attributable to the severity of CAD and oxidative stress levels in all included patients undergoing CABG.

Impact of the COVID-19 pandemic on cardiovascular mortality and catherization activity during the lockdown in central Germany: an observational study.

AIMS: During the COVID-19 pandemic, hospital admissions for cardiac care have declined. However, effects on mortality are unclear. Thus, we sought to evaluate the impact of the lockdown period in central Germany on overall and cardiovascular deaths. Simultaneously we looked at catheterization activities in the same region. METHODS AND RESULTS: Data from 22 of 24 public health-authorities in central Germany were aggregated during the pandemic related lockdown period and compared to the same time period in 2019. Information on the total number of deaths and causes of death, including cardiovascular mortality, were collected. Additionally, we compared rates of hospitalization (n = 5178) for chronic coronary syndrome (CCS), acute coronary syndrome (ACS), and out of hospital cardiac arrest (OHCA) in 26 hospitals in this area. Data on 5,984 deaths occurring between March 23, 2020 and April 26, 2020 were evaluated. In comparison to the reference non-pandemic period in 2019 (deaths: n = 5832), there was a non-significant increase in all-cause mortality of 2.6% [incidence rate ratio (IRR) 1.03, 95% confidence interval (CI) 0.99-1.06; p = 0.16]. Cardiovascular and cardiac mortality increased significantly by 7.6% (IRR 1.08, 95%-CI 1.01-1.14; p = 0.02) and by 11.8% (IRR 1.12, 95%-CI 1.05-1.19; p < 0.001), respectively. During the same period, our data revealed a drop in cardiac catherization procedures. CONCLUSION: During the COVID-19-related lockdown a significant increase in cardiovascular mortality was observed in central Germany, whereas catherization activities were reduced. The mechanisms underlying both of these observations should be investigated further in order to better understand the effects of a pandemic-related lockdown and social-distancing restrictions on cardiovascular care and mortality.

Necessity of Antiaggregation and Anticoagulation and Its Prognostic Impact: A Cardiologist's View.

BACKGROUND: In modern cardiology, anticoagulation and antiaggregation are key components of current treatment strategies. However, in patients treated with anticoagulation and antiplatelet substances, bleeding is a major risk. FINDINGS: In all major cardiovascular diseases, a multitude of studies have shown a positive impact of antithrombotic treatment on cardiovascular death. In patients with higher bleeding risks, recent studies showed the safety of reducing the period of dual antiplatelet therapy (DAPT), i.e., after percutaneous coronary intervention. In patients with coronary artery disease and atrial fibrillation (AF), triple therapy including DAPT and anticoagulation is associated with very high bleeding risks. However, recently published data showed the safety of direct oral anticoagulants (DOACs) and P2Y12 inhibitors only compared to vitamin K antagonist (VKA) and DAPT. Anticoagulation in nonvalvular AF reduces major cerebrovascular ischemic events. However, the inherent cerebrovascular bleeding risk is an important concern of this treatment. With the advent of DOACs, this risk could be reduced compared to VKA. Furthermore, anticoagulation and antiaggregation are crucial after treatment of valve disease, both after surgical and interventional procedures. Even in heart failure, new data show benefits using antithrombotic substances. CONCLUSIONS: Anticoagulation and antiaggregation are of major prognostic relevance in cardiovascular diseases. However, the inherent bleeding risk has to be considered.

Impact of percutaneous closure device type on vascular and bleeding complications after TAVR: A post hoc analysis from the BRAVO-3 randomized trial.

BACKGROUND/OBJECTIVE: Prostar XL (PS) and ProGlide (PG) are common vascular closure devices (VCD) used in TAVR via transfemoral vascular approach. The impact of these VCD on vascular and bleeding complications remains unclear. METHODS: The BRAVO-3 trial randomized 802 patients undergoing transfemoral TAVR. We stratified patients according to type of VCD used and examined the 30-day incidence of major or minor vascular complications, major bleeding (BARC ≥3b), AKI and major adverse cardiac and cerebrovascular events (MACCE; death, myocardial infarction or stroke). RESULTS: A total of 746 (93%) patients were treated with either PS (n = 352, 47%) or PG (n = 394, 53%) VCD, without significant differences in successful deployment rate (PS 322 [91.2%] vs. PG 373 [94.2%] respectively, p = .20). PG was associated with a significantly lower incidence of major or minor vascular complications, compared to PS (adjusted OR: 0.54; 95% CI: 0.37-0.80; p < .01). Rates of acute kidney injury were also lower with the PG device. There was no significant difference between bleeding, MACCE, and death. CONCLUSIONS: Compared to PS, the PG VCD was associated with a lower rate of major or minor vascular complications and lower rates of AKI after transfemoral TAVR.

Oxidative Stress in Cardiac Tissue of Patients Undergoing Coronary Artery Bypass Graft Surgery: The Effects of Overweight and Obesity.

BACKGROUND: Obesity is one of the major cardiovascular risk factors and is associated with oxidative stress and myocardial dysfunction. We hypothesized that obesity affects cardiac function and morbidity by causing alterations in enzymatic redox patterns. METHODS: Sixty-one patients undergoing coronary artery bypass grafting (CABG) were included in the study. Excessive right atrial myocardial tissue emerging from the operative connection to the extracorporeal circulation was harvested. Patients were assigned to control (n = 19, body mass index (BMI): <25 kg/m2), overweight (n = 25, 25 kg/m2 < BMI < 30 kg/m2), or obese (n = 17, BMI: >30 kg/m2) groups. Oxidative enzyme systems were studied directly in the cardiac muscles of patients undergoing CABG who were grouped according to BMI. Molecular biological methods and high-performance liquid chromatography were used to detect the expression and activity of oxidative enzymes and the formation of reactive oxygen species (ROS). RESULTS: We found increased levels of ROS and increased expression of ROS-producing enzymes (i.e., p47phox, xanthine oxidase) and decreased antioxidant defense mechanisms (mitochondrial aldehyde dehydrogenase, heme oxygenase-1, and eNOS) in line with elevated inflammatory markers (vascular cell adhesion molecule-1) in the right atrial myocardial tissue and by trend also in serum (sVCAM-1 and CCL5/RANTES). CONCLUSION: Increasing BMI in patients undergoing CABG is related to altered myocardial redox patterns, which indicates increased oxidative stress with inadequate antioxidant compensation. These changes suggest that the myocardium of obese patients suffering from coronary artery disease is more susceptible to cardiomyopathy and possible damage by ischemia and reperfusion, for example, during cardiac surgery.

An FFRCT diagnostic strategy versus usual care in patients with suspected coronary artery disease planned for invasive coronary angiography at German sites: one-year results of a subgroup analysis of the PLATFORM (Prospective Longitudinal Trial of FFRCT: Outcome and Resource Impacts) study.

AIM: Diagnostic evaluation practices for suspected coronary artery disease (CAD) may vary between countries. Our objective was to compare a CT-derived fractional flow reserve (FFRCT) diagnostic strategy with usual care in patients with planned invasive coronary angiography (ICA) enrolled in the PLATFORM (Prospective Longitudinal Trial of FFRCT: Outcome and Resource Impacts) study at German sites. METHODS: Patients were divided into two consecutive observational cohorts, receiving either usual care or CT angiography (CTA)/FFRCT. The primary endpoint was the percentage of patients planned for ICA, with no obstructive CAD on ICA within 90 days. Secondary endpoints included death, myocardial infarction, unstable angina, hospitalisation leading to unplanned revascularisation, cumulative radiation exposure, estimated medical costs and quality of life (QOL) at 1 year. RESULTS: 116 patients were included. The primary endpoint occurred in 4 of the 52 patients (7.7%) in the CTA/FFRCT group and in 55 of the 64 patients (85.9%) in the usual care group (risk difference 78.2%, 95% CI 67.1% to 89.4%, p<0.001). ICA was cancelled in 40 of the 52 patients (77%) who underwent CTA/FFRCT. Clinical event rates were low overall. The mean radiation exposure was lower in the FFRCT versus the usual care group (7.28 vs 9.80 mSv, p<0.001). Mean estimated medical costs were €4217 (CTA/FFRCT) versus €6894 (usual care), p<0.001. Improvement in QOL (EQ-5D score) was greater in the FFRCT (+0.09 units) versus the usual care cohort (+0.03 units), p=0.04. CONCLUSIONS: In patients with suspected CAD planned for ICA at German sites, initial CTA/FFRCT compared with usual care was associated with a markedly reduced rate of ICA showing no obstructive CAD, lower cumulative radiation exposure and estimated costs and greater improvement in QOL.

Effect of valve design and anticoagulation strategy on 30-day clinical outcomes in transcatheter aortic valve replacement: Results from the BRAVO 3 randomized trial.

BACKGROUND: Selection of valve type and procedural anticoagulant may impact bleeding and vascular complications in transfemoral transcatheter aortic valve replacement (TAVR). We sought to compare outcomes by valve [balloon expandable (BE) or non-BE] and anticoagulant [bivalirudin vs. unfractionated heparin (UFH)] type from the BRAVO-3 trial. METHODS: BRAVO-3 was a randomized multicenter trial including 500 BE-TAVR and 282 non-BE TAVR patients, randomized to bivalirudin versus UFH. Selection of valve type was at the discretion of the operator but randomization was stratified according to valve type. Total follow up was to 30 days. We examined the incidence of Bleeding Academic Research Consortium type ≥3b bleeding, major vascular complications and all ischemic outcomes at 30-days. Outcomes were adjusted using logistic regression analysis. RESULTS: Of the trial cohort, 63.9% were treated with BE valves (n = 251 bivalirudin vs. n = 249 UFH) and 36.1% with non-BE valves (n = 140 bivalirudin vs. n = 142 UFH). Patients treated with non-BE valves were older, with higher euroSCORE I. At 30 days, there were nonsignificant differences between the two valve types for adjusted risk of all-cause death (HR 2.07, 95% CI 0.91-4.70, P = 0.084) and major vascular complications (HR 1.78, 95% CI 0.97-3.26, P = 0.062) with non-BE compared with BE valves, but all other outcomes were similar. A significant interaction was observed between valve and anticoagulant type, with lower risk of major vascular complications with bivalirudin compared with UFH in non-BE TAVR (P-interaction = 0.039). CONCLUSIONS: Majority of patients in the BRAVO 3 trial received BE valves. At 30-days, adjusted risk of clinical outcomes was similar with non-BE vs. BE valves. A significant interaction was observed between valve type and procedural anticoagulant for lower risk of major vascular complications with bivalirudin versus UFH in non-BE TAVR.

Effects of atrial fibrillation and heart rate on percutaneous mitral valve repair with MitraClip: results from the TRAnscatheter Mitral valve Interventions (TRAMI) registry.

AIMS: In patients undergoing percutaneous edge-to-edge mitral valve repair for mitral valve regurgitation (MR), our aim was to evaluate acute and follow-up differences with pre-existing sinus rhythm (SR) or atrial fibrillation (AF), as well as comparisons stratified by baseline heart rate. METHODS AND RESULTS: Seven hundred and sixty patients who underwent a MitraClip procedure were prospectively enrolled in the TRAnscatheter Mitral valve Interventions (TRAMI) registry, and stratified according to baseline heart rhythm and heart rate with a cut-off value of 70 beats per minute. Technical success, procedural characteristics and MR reduction were similar throughout the subgroups. Overall, in-hospital adverse event rates were low in this high-risk patient collective. At 12 months, survival was higher in SR (83.5%) than AF patients (74.9%, p<0.05), while the cumulative major adverse cardio-cerebrovascular event rate did not differ, and a sustained improvement of NYHA functional class occurred in all subgroups. CONCLUSIONS: These registry data, comprising the largest number of unselected "real-world" MitraClip patients, suggest that the intervention can be performed safely and effectively, and reduces MR in the majority of patients irrespective of baseline rhythm or heart rate. While 12-month survival was higher for patients with SR, overall MACCE and clinical improvement did not differ between the subgroups.

Comparison of transcatheter aortic valve implantation with the newest-generation Sapien 3 vs. Direct Flow Medical valve in a single center cohort.

BACKGROUND: The latest generation transcatheter heart valves including Edwards Sapien 3 (ES3) and Direct Flow Medical (DFM) were designed to allow precise implantation at the intended position and to minimize prosthesis dysfunction as well as procedural complications. Our aim was to compare short-term functional and clinical outcomes of these 2 transcatheter aortic valve systems. METHODS: Of 174 patients undergoing transfemoral transcatheter aortic valve implantation (TAVI) at our institution between August 2013 and June 2015, 113 were treated with ES3 and 61 with DFM. Device success, residual aortic regurgitation and early safety endpoints were defined according to the updated VARC-2 criteria and prespecified as primary endpoints. RESULTS: Patients treated with ES3 had a significantly higher rate of procedural success (ES3 94% vs. DFM 79%, p=0.005), mainly driven by lower postprocedural gradients (ES3 8.6±0.5mmHg vs. DFM 14.6±1.4mmHg by invasive recordings; p=0.00012) and no incidence of more than mild aortic regurgitation. The occurrence of safety endpoints at 30days was low and comparable in the DFM vs. ES3 group (ES3 88% vs. DFM 95% of patients without endpoints, p=0.26). No significant differences were observed in 30day mortality, stroke or the incidence of new permanent pacemaker implantation. CONCLUSIONS: These single-center experience data show a higher rate of device success for ES3 treated patients, while 30day safety outcome was similar in both groups. Long-term follow-up and larger scale multicenter experience will have to assess possible effects of these observations on long-term clinical outcomes.

A systematic diagnostic and therapeutic approach for the treatment of patients after cardio-pulmonary resuscitation: a prospective evaluation of 212 patients over 5 years.

A literature on systematic treatment protocols for patients after resuscitation for cardiac arrest is lacking. We evaluated a systematic protocol, including ECG, echocardiogram, urgent cardiac catheterisation ("STEMI-like" workflow), CT scans, laboratory findings, IABP, hypothermia, and cMRI, prospectively over 5 years. The primary endpoint was the Cerebral Performance Category Scale (CPCS). During the period from January 2008 to December 2012, 212 patients were included. The mean age was 66.7 years, n = 151 (71.2 %) were male, mean time from the first medical contact to start of catheterisation was 76.6 min, and ventricular fibrillation (VF) was present in n = 99 (46.7 %). A significant coronary artery stenosis was seen in n = 130 (61.3 %), PCI was performed in n = 101 (47.6 %), an ACS was found in n = 100 (47.2 %), n = 91 patients (42.9 %) had another cardiac cause, an extra-cardiac cause was found in n = 12 (5.7 %, mostly a cerebral process), and in 9 patients (4.3 %), no cause was identifiable. A significant difference in mortality was found for patients with TIMI flow 2/3 vs. 0/1 (65.4 vs. 95.7 %, p < 0.01). The difference of intra-aortic balloon pumping vs. no pumping was not significant, performing hypothermia reduced mortality significantly (52.7 vs. 68.2 %, p = 0.04). The survival rate was n = 76 (35.9 %), a CPCS of 1/2 was reached in n = 68 pts (32.1 %), patients with ongoing resuscitation had a 100 % mortality (n = 41), and VF had a lower mortality (54.6 vs. 72.6 %, p < 0.01). A systematic algorithm may improve the outcome of patients after reanimation compared with classically reported outcomes. The data are hypothesis generating for further studies.

A multicentre European registry to evaluate the Direct Flow Medical transcatheter aortic valve system for the treatment of patients with severe aortic stenosis.

AIMS: Our aim was to assess the clinical outcomes of the Direct Flow Medical Transcatheter Aortic Valve System (DFM-TAVS), when used in routine clinical practice. METHODS AND RESULTS: This is a prospective, open-label, multicentre, post-market registry of patients treated with DFM-TAVS according to approved commercial indications. Echocardiographic and angiographic data were evaluated by an independent core laboratory and adverse events were adjudicated and classified according to VARC-2 criteria by an independent clinical events committee. The primary endpoint was freedom from all-cause mortality at 30 days post procedure. Secondary endpoints included procedural, early safety and efficacy endpoints at 30 days. Two hundred and fifty patients with severe aortic stenosis undergoing transcatheter aortic valve implantation (TAVI) with the DFM-TAVS were enrolled in 21 European centres. The primary endpoint, freedom from all-cause mortality at 30 days, was met in 98% (245/250) of patients. Device success was 83.8%. Moderate or severe aortic regurgitation was reported in 3% of patients, and none/trace regurgitation in 73% of patients. Post-procedural permanent pacemaker implantation was performed in 30 patients (12.0%). CONCLUSIONS: The DFM-TAVS was associated with good short-term outcomes in this real-world registry. The low pacemaker and aortic regurgitation rates confirm the advantages of this next-generation transcatheter heart valve (THV).

1-Year Outcomes of FFRCT-Guided Care in Patients With Suspected Coronary Disease: The PLATFORM Study.

BACKGROUND: Coronary computed tomographic angiography (CTA) plus estimation of fractional flow reserve using CTA (FFRCT) safely and effectively guides initial care over 90 days in patients with stable chest pain. Longer-term outcomes are unknown. OBJECTIVES: The study sought to determine the 1-year clinical, economic, and quality-of-life (QOL) outcomes of using FFRCT instead of usual care. METHODS: Consecutive patients with stable, new onset chest pain were managed by either usual testing (n = 287) or CTA (n = 297) with selective FFRCT (submitted in 201, analyzed in 177); 581 of 584 (99.5%) completed 1-year follow-up. Endpoints were adjudicated major adverse cardiac events (MACE) (death, myocardial infarction, unplanned revascularization), total medical costs, and QOL. RESULTS: Patients averaged 61 years of age with a mean 49% pre-test probability of coronary artery disease. At 1 year, MACE events were infrequent, with 2 in each arm of the planned invasive group and 1 in the planned noninvasive cohort (usual care strategy). In the planned invasive stratum, mean costs were 33% lower with CTA and selective FFRCT ($8,127 vs. $12,145 usual care; p < 0.0001); in the planned noninvasive stratum, mean costs did not differ when using an FFRCT cost weight of zero ($3,049 FFRCT vs. $2,579; p = 0.82), but were higher when using an FFRCT cost weight equal to CTA. QOL scores improved overall at 1 year (p < 0.001), with similar improvements in both groups, apart from the 5-item EuroQOL scale scores in the noninvasive stratum (mean change of 0.12 for FFRCT vs. 0.07 for usual care; p = 0.02). CONCLUSIONS: In patients with stable chest pain and planned invasive coronary angiography, care guided by CTA and selective FFRCT was associated with equivalent clinical outcomes and QOL, and lower costs, compared with usual care over 1-year follow-up. (The PLATFORM Study: Prospective LongitudinAl Trial of FFRct: Outcome and Resource IMpacts [PLATFORM]; NCT01943903).

Transcatheter aortic valve implantation with the new-generation Evolut R™: Comparison with CoreValve® in a single center cohort.

BACKGROUND: The Medtronic Evolut R (EVR) is a novel transcatheter heart valve designed to allow precise implantation at the intended position and to minimize prosthesis dysfunction as well as procedural complications. Our aim was to compare short-term functional and clinical outcomes of the new EVR with the established Medtronic CoreValve (CV) system. METHODS AND RESULTS: Of 151 patients undergoing transfemoral transcatheter aortic valve implantation with a self-expanding valve at our institution between January 2013 and January 2016, 86 were treated with EVR and 65 with CV. Patients treated with EVR had a significantly lower rate of more-than-mild aortic regurgitation and a higher rate of device success. Recapture maneuvers to optimize valve deployment were performed in 22.1% of the EVR procedures. Transvalvular post-procedural gradients were slightly higher in the EVR group, while no differences were observed in the incidence of safety endpoints at 30 days, vascular complications, or need for permanent pacemaker implantation following asystole or complete atrioventricular block. CONCLUSIONS: These initial single-center experience data on the short-term outcomes after EVR valve implantation show a substantially reduced rate of more-than-mild paravalvular regurgitation and higher device success, while 30-day safety outcomes were similar to the CV system. Clinical outcome data from long-term follow-up and larger scale multicenter experience are now necessary.

Quality-of-Life and Economic Outcomes of Assessing Fractional Flow Reserve With Computed Tomography Angiography: PLATFORM.

BACKGROUND: Fractional flow reserve estimated using computed tomography (FFRCT) might improve evaluation of patients with chest pain. OBJECTIVES: The authors sought to determine the effect on cost and quality of life (QOL) of using FFRCT instead of usual care to evaluate stable patients with symptoms suspicious for coronary disease. METHODS: Symptomatic patients without known coronary disease were enrolled into 2 strata based on whether invasive or noninvasive diagnostic testing was planned. In each stratum, consecutive observational cohorts were evaluated with either usual care or FFRCT. The number of diagnostic tests, invasive procedures, hospitalizations, and medications during 90-day follow-up were multiplied by U.S. cost weights and summed to derive total medical costs. Changes in QOL from baseline to 90 days were assessed using the Seattle Angina Questionnaire, the EuroQOL, and a visual analog scale. RESULTS: In the 584 patients, 74% had atypical angina, and the pre-test probability of coronary disease was 49%. In the planned invasive stratum, mean costs were 32% lower among the FFRCT patients than among the usual care patients ($7,343 vs. $10,734 p < 0.0001). In the noninvasive stratum, mean costs were not significantly different between the FFRCT patients and the usual care patients ($2,679 vs. $2,137; p = 0.26). In a sensitivity analysis, when the cost weight of FFRCT was set to 7 times that of computed tomography angiography, the FFRCT group still had lower costs than the usual care group in the invasive testing stratum ($8,619 vs. $ 10,734; p < 0.0001), whereas in the noninvasive testing stratum, when the cost weight of FFRCT was set to one-half that of computed tomography angiography, the FFRCT group had higher costs than the usual care group ($2,766 vs. $2,137; p = 0.02). Each QOL score improved in the overall study population (p < 0.0001). In the noninvasive stratum, QOL scores improved more in FFRCT patients than in usual care patients: Seattle Angina Questionnaire 19.5 versus 11.4, p = 0.003; EuroQOL 0.08 versus 0.03, p = 0.002; and visual analog scale 4.1 versus 2.3, p = 0.82. In the invasive cohort, the improvements in QOL were similar in the FFRCT and usual care patients. CONCLUSIONS: An evaluation strategy based on FFRCT was associated with less resource use and lower costs within 90 days than evaluation with invasive coronary angiography. Evaluation with FFRCT was associated with greater improvement in quality of life than evaluation with usual noninvasive testing. (Prospective Longitudinal Trial of FFRCT: Outcomes and Resource Impacts [PLATFORM]; NCT01943903).

Rationale and design of the Prospective LongitudinAl Trial of FFRCT: Outcome and Resource IMpacts study.

BACKGROUND: Fractional flow reserve (FFR) measured by coronary computed tomography angiography (FFRCT) has been validated against invasive FFR. However, there are no data on how the use of FFRCT affects patient care and outcomes. The aim of this study is to compare standard practice guided by usual care testing to FFRCT-guided management in symptomatic subjects with suspected coronary artery disease (CAD). METHODS: In this prospective nonrandomized trial, symptomatic patients with suspected CAD will be enrolled in 2 consecutive cohorts: a usual care-guided pathway (cohort 1) and an FFRCT-guided pathway (cohort 2). Each cohort is divided into 2 groups according to whether noninvasive or invasive diagnostic testing was planned before enrollment. In all subjects, the patient's clinical team will review all diagnostic test results and determine a treatment strategy. A total sample size of 580 subjects will be enrolled and followed up for 12 months. RESULTS: The primary end point is the comparison of the percentage of patients with planned invasive testing who have a catheterization (invasive coronary angiography) within 90 days from initial assessment, which does not show a significant stenosis (defined as coronary artery stenosis >50% or invasive FFR ≤0.80). Secondary end points include the rate of invasive coronary angiography without obstructive CAD in those with planned noninvasive testing and, in all groups, noninferiority of resource use, quality of life, medical radiation exposure, and major adverse cardiac events up to 365 days of follow-up. CONCLUSIONS: The study compares clinical and economic outcomes based on diagnostic evaluation using FFRCT with that based on standard diagnostic strategies.

Clinical outcomes of fractional flow reserve by computed tomographic angiography-guided diagnostic strategies vs. usual care in patients with suspected coronary artery disease: the prospective longitudinal trial of FFR(CT): outcome and resource impacts study.

AIMS: In symptomatic patients with suspected coronary artery disease (CAD), computed tomographic angiography (CTA) improves patient selection for invasive coronary angiography (ICA) compared with functional testing. The impact of measuring fractional flow reserve by CTA (FFRCT) is unknown. METHODS AND RESULTS: At 11 sites, 584 patients with new onset chest pain were prospectively assigned to receive either usual testing (n = 287) or CTA/FFR(CT) (n = 297). Test interpretation and care decisions were made by the clinical care team. The primary endpoint was the percentage of those with planned ICA in whom no significant obstructive CAD (no stenosis ≥50% by core laboratory quantitative analysis or invasive FFR < 0.80) was found at ICA within 90 days. Secondary endpoints including death, myocardial infarction, and unplanned revascularization were independently and blindly adjudicated. Subjects averaged 61 ± 11 years of age, 40% were female, and the mean pre-test probability of obstructive CAD was 49 ± 17%. Among those with intended ICA (FFR(CT)-guided = 193; usual care = 187), no obstructive CAD was found at ICA in 24 (12%) in the CTA/FFR(CT) arm and 137 (73%) in the usual care arm (risk difference 61%, 95% confidence interval 53-69, P< 0.0001), with similar mean cumulative radiation exposure (9.9 vs. 9.4 mSv, P = 0.20). Invasive coronary angiography was cancelled in 61% after receiving CTA/FFR(CT) results. Among those with intended non-invasive testing, the rates of finding no obstructive CAD at ICA were 13% (CTA/FFR(CT)) and 6% (usual care; P = 0.95). Clinical event rates within 90 days were low in usual care and CTA/FFR(CT) arms. CONCLUSIONS: Computed tomographic angiography/fractional flow reserve by CTA was a feasible and safe alternative to ICA and was associated with a significantly lower rate of invasive angiography showing no obstructive CAD.

Clinical, Angiographic, Functional, and Imaging Outcomes 12 Months After Implantation of Drug-Eluting Bioresorbable Vascular Scaffolds in Acute Coronary Syndromes.

OBJECTIVES: The purpose of this study was to describe the multimodal outcome 12 months after implantation of coronary bioresorbable scaffolds (BVS) for the treatment of patients with acute coronary syndromes (ACS). BACKGROUND: Functional and imaging data on the use of BVS are limited to simple, stable lesions; in the setting of ACS, only short-term clinical follow-up data are available, and no information from intracoronary imaging and vasomotion tests has been reported. METHODS: A total of 133 patients (age 62 ± 12 years, 74% males, 15% diabetic) underwent BVS (n = 166) implantation for the treatment of thrombotic lesions in the setting of ACS (43% non-ST-segment elevation myocardial infarction, 38% ST-segment elevation myocardial infarction, 20% unstable angina). Clinical, angiographic, intracoronary imaging, and vasomotor endpoints were evaluated at 12 months. RESULTS: During the 374 days (interquartile range: 359 to 411 days) of follow-up, there were 4 deaths; 3 definite and 1 probable in-BVS thromboses (all in the first 6 months). At 12-month angiography (75 patients, 83 BVS), in-segment late lumen loss was 0.19 ± 0.45 mm, and 3 (4%) patients showed binary restenosis. Optical coherence tomography (80 BVS, n = 70) showed a mean lumen area of 6.3 ± 2.3 mm(2). Malapposition was evidenced in 21 (26%) BVS. Endothelium-dependent and -independent vasodilation were observed in 48% and 49% of the BVS. CONCLUSIONS: Twelve months after BVS implantation, clinical, intracoronary imaging, and vasomotion data appear to provide a rationale for the use of BVS in the setting of ACS and the basis for a randomized study.

Feasibility and safety of left ventricular endomyocardial biopsy via transradial access: Technique and initial experience.

BACKGROUND: Endomyocardial biopsy constitutes an essential part of the diagnostic algorithm in patients with heart failure of unknown origin, but usually requires transfemoral access. METHODS AND RESULTS: Here, we describe a novel method that allows interventional cardiologists to obtain left ventricular biopsies via transradial access with a 7.5F sheathless multipurpose (MP1.0) guiding catheter. This approach was successfully conducted in 37 consecutive patients at our institution with only one intraprocedural minor complication (ventricular fibrillation during insertion of the guiding catheter). CONCLUSIONS: Transradial access to obtain left ventricular endomyocardial biopsies is a feasible and safe option for experienced radial operators.

Usefulness of 3D-PISA as compared to guideline endorsed parameters for mitral regurgitation quantification.

This study was intended to evaluate the diagnostic value of three dimensional proximal isovelocity surface area (3D PISA) derived effective regurgitant orifice area (EROA) and the accuracy of automatic 3D PISA detection in a population resembling clinical practice. Quantification of mitral regurgitation (MR) remains challenging and 3D PISA EROA is a novel diagnostic tool with promising results. However its' usefulness compared to guideline endorsed parameters has not been shown. In 93 consecutive patients examined in routine practice conventional parameters and 3D-datasets for offline 3D PISA evaluation were recorded. EROA was determined from the largest (peak) PISA and also averaged over systole for meanEROA. Results of 3D PISA calculation were compared with a combination of expert grading by two examiners and two scores for MR grading. In receiver operator characteristic-analysis the meanEROA as determined by 3D PISA had the best diagnostic value (AUC = 0.907 CI 0.832-0.983) as compared to peakEROA (AUC 0.840 CI 0.739-0.941), vena contracta width (AUC 0.831 CI 0.745-0.918) and 2D PISA (AUC 0.747 CI 0.644-0.850). A meanEROA of 0.15 cm(2) had a sensitivity of 88.2 % and a specificity of 81.4 % for distinguishing severe from non-severe MR. Semiautomatic 3D PISA detection correlated very well with manually corrected values (r = 0.955). Semiautomatic 3D PISA measurement is feasible in a clinical population and has better diagnostic value compared to 2D PISA. Calculation of mean EROA throughout systole further improves diagnostic value compared to conventional parameters.

Impact of the learning curve on outcome after transcatheter mitral valve repair: results from the German Mitral Valve Registry.

AIMS: This analysis from the German Mitral Valve Registry investigates the impact of the learning curve with the MitraClip(®) technique on procedural success and complications. METHODS AND RESULTS: Consecutive patients treated since 2009 in centers that performed more than 50 transcatheter mitral repairs were included. Results of the first half of the patients were compared to those of the second. Altogether 496 patients from 10 centers were included. Patients treated later had less common severe heart failure symptoms (patients with NYHA IV: 22.1 vs. 14.5 %, p < 0.05). The EuroSCORE I (22.0 vs. 23.0 %, p = ns) and Society of Thoracic Surgeons (STS) score (7.5 vs. 9.5 %, p = ns) did not differ between both groups. Procedural success was 95.6 % (238/249) in the first cases and 94.7 % (232/245, p = ns) subsequently. Also procedural time (104.3 vs. 119 min, p = ns) and complications did not decrease over time. CONCLUSION: A learning curve using the MitraClip(®) device does not appear to significantly affect acute MR reduction, hospital and 30-day mortality. Most likely, the proctor system leads to already high initial procedure success and relatively short procedure time.