Prevalence and Impact of Frailty in Patients ≥70 Years Old with Acute Coronary Syndrome Referred for Coronary Angiography.

INTRODUCTION: Elderly patients with acute coronary syndrome (ACS) have a higher risk of adverse cardiovascular events and may be frail but are underrepresented in clinical trials. Previous studies have proposed that frailty assessment is a better tool than chronological age, in assessing older patients' biological age, and may exceed conventional risk scores in predicting the prognosis. Therefore, we wanted to investigate the prevalence and impact on 12-month outcomes of frailty in patients ≥70 years with ACS referred for coronary angiography (CAG). METHODS: Patients ≥70 years with ACS referred for CAG underwent frailty scoring with the clinical frailty scale (CFS). Patients were divided into three groups depending on their CFS: robust (1-3), vulnerable (4), and frail (5-9) and followed for 12 months. RESULTS: Of 455 patients, 69 (15%) patients were frail, 79 (17%) were vulnerable, and 307 (68%) were robust. Frail patients were older (frail: 80.9 ± 5.7 years, vulnerable: 78.5 ± 5.5 years, and robust: 76.6 ± 4.9 years, p < 0.001) and less often treated with percutaneous coronary intervention (frail: 56.5%, vulnerable: 53.2%, and robust: 68.6%, p = 0.014). 12-month mortality was higher among frail patients (frail: 24.6%, vulnerable: 21.8%, and robust: 6.2%, p < 0.001). Frailty was associated with a higher mortality after adjustment for age, sex, comorbidities, the Global Registry of Acute Coronary Events (GRACE) score, and revascularisation (HR 2.67, 95% CI 1.30-5.50, p = 0.008). There was no difference between GRACE and CFS in predicting 12-month mortality (p = 0.893). CONCLUSIONS: Fifteen percent of patients ≥70 years old with ACS referred for CAG are frail. Frail patients have significantly higher 12-month mortality. GRACE and CFS are similar in predicting 12-month mortality.

Is It Safe to Mobilize Patients Very Early After Transfemoral Coronary Procedures? (SAMOVAR): A Randomized Clinical Trial.

BACKGROUND: Coronary angiography (CAG) and percutaneous coronary intervention (PCI) are performed via the femoral or radial arteries. In patients examined via transfemoral access, closure devices facilitate hemostasis, but it is unknown whether it is safe to mobilize these patients immediately and how acceptable this may be in terms of patient comfort. OBJECTIVE: The aims of this study were to investigate bleeding complications in patients mobilized immediately after transfemoral CAG or PCI compared with patients on bed rest (BR) for 2 hours after the procedure and, furthermore, to investigate patient comfort in relation to mobilization and BR. METHODS: SAMOVAR was a noninferiority trial with patients randomized to immediate mobilization (IM) or 2 hours of BR after transfemoral CAG or PCI and use of the AngioSeal as a closure device and reversal of heparin effect. The primary end point was development of hematoma greater than 5 cm, pseudoaneurysm, or bleeding requiring blood transfusion. Secondary end points were oozing from the puncture site, small hematoma, and patient comfort. RESULTS: Of 2027 patients (IM, 1010; BR, 1017), 40% underwent PCI. The primary outcome was recorded in 0.7% patients randomized to IM versus 0.5% in BR ( P = .58). There was no difference in the incidence of small hematoma, whereas persistent oozing was seen slightly more often after IM compared with BR (12% vs 9%, P = .04). Patients mobilized immediately reported less back pain and micturition problems ( P < .001). CONCLUSIONS: In patients who had CAG and PCI performed through transfemoral access, reversal of anticoagulation and use of closure devices allowed IM with low rates of complications and improved patient comfort.

The benefit of complete revascularization after primary PCI for STEMI is attenuated by increasing age: Results from the DANAMI-3-PRIMULTI randomized study.

OBJECTIVES: To ascertain the effect of age on outcomes after culprit-only and complete revascularization after Primary PCI (PPCI) for ST-elevation myocardial infarction (STEMI). BACKGROUND: The numbers of older patients being treated with PPCI are increasing. The optimal management of nonculprit stenoses in such patients is unclear. METHODS: We conducted an analysis of patients aged ≥75 years randomized in the DANAMI-3-PRIMULTI study to either culprit-only or complete FFR-guided revascularization. The primary endpoint was a composite of all-cause mortality, nonfatal reinfarction, and ischaemia-driven revascularization of lesions in noninfarct-related arteries after a median of 27 months of follow-up. RESULTS: One hundred and ten of six hundred and twenty seven patients in the DANAMI-3-PRIMULTI trial were aged ≥75 years. These patients were more likely female (p < .001), hypertensive (p < .001), had lower hemoglobin levels (p < .001), and higher serum creatinine levels (p < .001) than the younger patients in the trial. Other than less use of drug-eluting stents (96.6 versus 88.0%: p = .02), there were no significant differences in procedural technique and success between patients aged <75 years and those ≥75 years of age. There was no significant difference in the incidence of the primary endpoint in patients ≥75 years randomized to culprit-only or FFR-guided complete revascularization (HR 1.49 [95% CI 0.57-4.65]; log-rank p = .19; p for interaction versus patients <75 years <.001). There was a significant interaction between age as a continuous variable, treatment assignment, and the primary outcome (p < .001); beyond the age of about 75 years, there may be no prognostic advantage to complete revascularization. CONCLUSIONS: In patients ≥75 years, after treatment of the culprit lesion in STEMI, there is no significant prognostic benefit to prophylactic complete revascularization of nonculprit stenoses. Pending further study, data would support a symptom-guided approach to further invasive treatment.

Electrocardiogram to predict reperfusion success in late presenters with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention.

BACKGROUND: Clinical decision-making in patients with ST-segment elevation myocardial infarction (STEMI) presenting beyond 12 h of symptom onset (late presenters) is challenging. However, the electrocardiogram (ECG) may provide helpful information. We investigated the association between three ECG-scores and myocardial salvage and infarct size in late presenters treated with primary percutaneous coronary intervention (primary PCI). METHODS: Sixty-six patients with STEMI and ongoing symptoms presenting 12-72 h after symptom onset were included. Cardiac magnetic resonance was performed at day 1 (interquartile range [IQR], 1-1) and at follow-up at day 93 (IQR, 90-98). The pre-PCI ECG was analyzed for the presence of pathological QW (early QW) as well as Anderson-Wilkins acuteness score (AW-score), the classic Sclarovsky-Birnbaum Ischemia Grading System (classic SB-IG-score) and a modified SB-IG-score including any T-wave morphologies. RESULTS: Early QW was associated with a larger myocardium at risk (39 ± 12 versus 33 ± 12; p = 0.030) and final infarct size (20 ± 11 versus 14 ± 9; p = 0.021) as well as a numerical lower final myocardial salvage (0.52 ± 0.19 versus 0.61 ± 0.23; p = 0.09). The association with final infarct size disappeared after adjusting for myocardium at risk. An AW-score < 3 showed a trend towards a larger final infarct size (18 ± 11 versus 11 ± 11; p = 0.08) and was not associated with salvage index (0.55 ± 0.20 versus 0.65 ± 0.30; p = 0.23). The classic and modified SB-IG-score were not associated with final infarct size (modified SB-IG-score, 17 ± 10 versus 21 ± 13; p = 0.28) or final myocardial salvage (0.53 ± 0.20 versus 0.53 ± 0.26; p = 0.96). CONCLUSION: Of three well-established ECG-scores only early QW and AW-score < 3 showed association with myocardium at risk and infarct size to some extent, but the association with myocardial salvage was weak. Hence, neither of the three investigated ECG-scores are sufficient to guide clinical decision-making in patients with STEMI and ongoing symptoms presenting beyond 12 h of symptom onset.

Invasive angiography and revascularization in patients with stable angina following prior coronary artery bypass grafting: Results from the East Denmark heart registry.

BACKGROUND: There are limited data to guide the optimum approach to patients presenting with angina after coronary artery bypass grafting (CABG). Although often referred for invasive angiography, the effectiveness of this is unknown; angina may also result from diffuse distal or micro-vascular coronary disease and it is not known how often targets for intervention are identified. METHODS: Retrospective review of 50,460 patients undergoing angiography in East Denmark between January 2010 and December 2014. Clinical and procedural data were prospectively stored in a regional electronic database. Follow-up data were available for all patients, by means of records linked to each Danish social security number. RESULTS: In patients with prior CABG and stable angina (n = 2,309), diagnostic angiography led to revascularization in 574 (24.9%) cases. Chronic kidney disease (HR 1.93 [1.08-3.44], P = 0.027), significant angina (HR 1.49 [1.18-1.88], P = 0.006 for angina class ≥ II, and HR 2.04 [1.61-2.58], P < 0.001 for angina class ≥ III) and a positive pre-procedural stress test (HR 2.56 [1.42-4.60], P < 0.001) were independent predictors of revascularization. Stress testing was, however, used less frequently than in patients without prior CABG (17.2% vs. 24.2%, P < 0.001). The positive predictive values for subsequent revascularization were 47.8%, 51.4%, and 66.9% for exercise ECG, stress echocardiography, and myocardial perfusion scintigraphy (MPS), respectively. CONCLUSIONS: Invasive angiography leads to revascularization in a quarter of patients with angina and prior CABG; the threshold for referral may be too low. Non-invasive stress testing predicts the need for revascularization but appears underused and MPS, in particular, may better identify patients likely to require revascularization. © 2016 Wiley Periodicals, Inc.

Organized thrombus is a frequent underlying feature in culprit lesion morphology in non-ST-elevation myocardial infarction. A study using optical coherence tomography and magnetic resonance imaging.

The concept that the culprit lesion in non-ST segment elevation myocardial infarction (NSTEMI) is caused by sudden plaque rupture with acute thrombus formation has recently been challenged. While angiography is an old gold-standard for culprit identification it merely visualizes the lumen contour. Optical coherence tomography (OCT) provides a detailed view of culprit features. Combined with myocardial edema on cardiac magnetic resonance (CMR), indicating acute ischemia and thus culprit location, we aimed to characterize culprit lesions using OCT. Patients with NSTEMI referred for angiography were prospectively enrolled. OCT was performed on angiographic stenoses ≥50% and on operator-suspected culprit lesions. Hierarchical OCT-culprit identifiers were defined in case of multiple unstable lesions, including OCT-defined thrombus age. An OCT-based definition of an organizing thrombus as corresponding to histological early healing stage was introduced. Lesions were classified as OCT-culprit or non-culprit, and characteristics compared. CMR was performed in a subset of patients. We included 65 patients with 97 lesions, of which 49 patients (75%) had 53 (54%) OCT-culprit lesions. The most common OCT-culprit identifiers were the presence of acute (66%) and organizing thrombus (19%). Plaque rupture was visible in 45% of OCT-culprit lesions. CMR performed in 38 patients revealed myocardial oedema in the corresponding territories of 67% of acute thrombi and 50% of organizing thrombi. A culprit lesion was identified by OCT in 75% patients with NSTEMI. Acute thrombus was the most frequent feature followed by organizing thrombus. Applying specific OCT-criteria to identify the culprit could prove valuable in ambiguous cases.

Anti-tumor necrosis factor-α therapy reduces aortic inflammation and stiffness in patients with rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is a systemic inflammatory condition associated with increased cardiovascular risk. This is not fully explained by traditional risk factors, but direct vascular inflammation and aortic stiffening may play a role. We hypothesized that patients with RA exhibit aortic inflammation, which can be reversed with anti-tumor necrosis factor-α therapy and correlates with aortic stiffness reduction. METHODS AND RESULTS: Aortic inflammation was quantified in 17 patients with RA, before and after 8 weeks of anti-tumor necrosis factor-α therapy by using (18)F-fluorodeoxyglucose positron emission tomography with computed tomography coregistration. Concomitantly, 34 patients with stable cardiovascular disease were imaged as positive controls at baseline. Aortic fluorodeoxyglucose target-to-background ratios (TBRs) and aortic pulse wave velocity were assessed. RA patients had higher baseline aortic TBRs in comparison with patients who have cardiovascular disease (2.02±0.22 versus 1.74±0.22, P=0.0001). Following therapy, aortic TBR fell to 1.90±0.29, P=0.03, and the proportion of inflamed aortic slices (defined as TBR >2.0) decreased from 50±33% to 33±27%, P=0.03. Also, TBR in the most diseased segment of the aorta fell from 2.51±0.33 to 2.05±0.29, P<0.0001. Treatment also reduced aortic pulse wave velocity significantly (from 9.09±1.77 to 8.63±1.42 m/s, P=0.04), which correlated with the reduction of aortic TBR (R=0.60, P=0.01). CONCLUSIONS: This study demonstrates that RA patients have increased aortic (18)F-fluorodeoxyglucose uptake in comparison with patients who have stable cardiovascular disease. Anti-tumor necrosis factor-α therapy reduces aortic inflammation in patients with RA, and this effect correlates with the decrease in aortic stiffness. These results suggest that RA patients exhibit a subclinical vasculitis, which provides a mechanism for the increased cardiovascular disease risk seen in RA.

Long-term changes in coronary physiology after aortic valve replacement.

BACKGROUND: The detrimental effects of long-standing severe aortic stenosis (AS) often include left ventricular hypertrophy (LVH) and exhaustion of coronary flow reserve (CFR), the reversibility of which is unclear after valve replacement. AIMS: Our aims were to 1) investigate whether CFR in the left anterior descending artery (LAD) would improve following valve replacement, and if the change was related to changes in hyperaemic coronary flow (QLAD) and minimal microvascular resistance (Rµ,LAD); and 2) investigate the relationship between changes in CFR and changes in left ventricular mass (LVM) and stroke work (LVSW). METHODS: We measured intracoronary bolus thermodilution-derived CFR, and continuous thermodilution-derived QLAD and Rµ,LAD before and 6 months after aortic valve replacement. Cardiac magnetic resonance imaging was used to quantify left ventricular anatomy and function for the calculation of LVM and LVSW.  Results: Thirty-four patients were included (17 patients had transcatheter aortic valve implantation; 14 had surgical valve replacement with a bioprosthesis and 3 with a mechanical prosthesis) who underwent invasive assessment in the LAD. CFR increased from 2.5 (interquartile range [IQR] 1.5-3.3) at baseline to 3.1 (IQR 2.2-5.1) at follow-up (p=0.005), despite no significant change in QLAD (230±106 mL/min to 250±101 mL/min; p=0.26) or Rµ,LAD (347 [IQR 247-463] to 287 [IQR 230-456]; p=0.20). When indexed for LVM, QLAD was 39% (IQR 8-98%) higher at follow-up compared with baseline (p<0.001). The improvement in CFR was correlated with ΔLVSW, r= -0.39; p=0.047.   Conclusions: CFR in the LAD increased significantly at follow-up although global hyperaemic flow and minimal microvascular resistance remained unchanged. Thus, a decrease in resting flow was the cause of CFR improvement. CFR improvement was associated with reduction in LVSW.

Coronary CT and timing of invasive coronary angiography in patients ≥75 years old with non-ST segment elevation acute coronary syndromes.

BACKGROUND: The ability of coronary CT angiography (cCTA) to rule out significant coronary artery disease (CAD) in older patients with non-ST segment elevation acute coronary syndromes (NSTEACS) is unclear since valid cCTA analysis may be limited by extensive coronary artery calcification. In addition, the effect of very early invasive coronary angiography (ICA) with possible revascularisation is debated. METHODS: This is a posthoc analysis of patients ≥75 years included in the Very Early vs Standard Care Invasive Examination and Treatment of Patients with Non-ST-Segment Elevation Acute Coronary Syndrome Trial. cCTA was performed prior to the ICA. The diagnostic accuracy of cCTA was investigated. Presence of a coronary artery stenosis ≥50% by subsequent ICA was used as reference. Patients were randomised to a very early (within 12 hours of diagnosis) or a standard ICA (within 48-72 hours of diagnosis). The primary composite endpoint was 5-year all-cause mortality, non-fatal recurrent myocardial infarction or hospital admission for refractory myocardial ischaemia or heart failure. RESULTS: Of 452 (21%) patients ≥75 years, 161 (35.6%) underwent cCTA. 19% of cCTAs excluded significant CAD. The negative predictive value (NPV) of cCTA was 94% (95% CI 79 to 99) and the sensitivity 98% (95% CI 94 to 100). No significant differences in the frequency of primary endpoints were seen in patients randomised to very early ICA (at 5-year follow-up, n=100 (46.9%) vs 122 (51.0%), log-rank p=0.357). CONCLUSION: In patients ≥75 years with NSTEACS, cCTA before ICA showed a high NPV. A very early ICA <12 hours of diagnosis did not significantly improve long-term clinical outcomes.

Danish phase II trial using adipose tissue derived mesenchymal stromal cells for patients with ischaemic heart failure.

AIMS: Patients suffering from chronic ischaemic heart failure with reduced left ventricular ejection fraction (HFrEF) have reduced quality-of-life, repetitive hospital admissions, and reduced life expectancy. Allogeneic cell therapy is currently investigated as a potential treatment option after initially encouraging results from clinical autologous and allogeneic trials in patients with HFrEF. We aimed to investigate the allogeneic Cardiology Stem Cell Centre Adipose tissue derived mesenchymal Stromal Cell product (CSCC_ASC) as an add-on therapy in patients with chronic HFrEF. METHODS AND RESULTS: This is a Danish multi-centre double-blinded placebo-controlled phase II study with direct intra-myocardial injections of allogeneic CSCC_ASC. A total of 81 HFrEF patients were included and randomized 2:1 to CSCC_ASC or placebo injections. The inclusion criteria were reduced left ventricular ejection fraction (LVEF ≤ 45%), New York Heart Association (NYHA) class II-III despite optimal anti-congestive heart failure medication and no further revascularization options. Injections of 0.3 mL CSCC_ASC (total cell dose 100 × 106 ASCs) (n = 54) or isotonic saline (n = 27) were performed into the viable myocardium in the border zone of infarcted tissue using the NOGA Myostar® catheter (Biological Delivery System, Cordis, Johnson & Johnson, USA). The primary endpoint, left ventricular end systolic volume (LVESV), was evaluated at 6-month follow-up. The safety was measured during a 3-years follow-up period. RESULTS: Mean age was 67.0 ± 9.0 years and 66.6 ± 8.1 years in the ASC and placebo groups, respectively. LVESV was unchanged from baseline to 6-month follow-up in the ASC (125.7 ± 68.8 mL and 126.3 ± 72.5 mL, P = 0.827) and placebo (134.6 ± 45.8 mL and 135.3 ± 49.6 mL, P = 0.855) group without any differences between the groups (0.0 mL (95% CI -9.1 to 9.0 mL, P = 0.992). Neither were there significant changes in left ventricular end diastolic volume or LVEF within the two groups or between groups -5.7 mL (95% CI -16.7 to 5.3 mL, P = 0.306) and -1.7% (95% CI -4.4. to 1.0, P = 0.212), respectively). NYHA classification and 6-min walk test did not alter significantly in the two groups (P > 0.05). The quality-of-life, total symptom, and overall summary score improved significantly only in the ASC group but not between groups. There were 24 serious adverse events (SAEs) in the ASC group and 11 SAEs in the placebo group without any significant differences between the two groups at 1-year follow-up. Kaplan-Meier plot using log-rank test of combined cardiac events showed an overall mean time to event of 30 ± 2 months in the ASC group and 29 ± 2 months in the placebo group without any differences between the groups during the 3 years follow-up period (P = 0.994). CONCLUSIONS: Intramyocardial CSCC_ASC injections in patients with chronic HFrEF were safe but did not improve myocardial function or structure, nor clinical symptoms.

Effect of allogeneic adipose tissue-derived mesenchymal stromal cell treatment in chronic ischaemic heart failure with reduced ejection fraction - the SCIENCE trial.

AIMS: The aim of the SCIENCE trial was to investigate whether a single treatment with direct intramyocardial injections of adipose tissue-derived mesenchymal stromal cells (CSCC_ASCs) was safe and improved cardiac function in patients with chronic ischaemic heart failure with reduced ejection fraction (HFrEF). METHODS AND RESULTS: The study was a European multicentre, double-blind, placebo-controlled phase II trial using allogeneic CSCC_ASCs from healthy donors or placebo (2:1 randomization). Main inclusion criteria were New York Heart Association (NYHA) class II-III, left ventricular ejection fraction (LVEF) <45%, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels >300 pg/ml. CSCC_ASCs or placebo (isotonic saline) were injected directly into viable myocardium. The primary endpoint was change in left ventricular end-systolic volume (LVESV) at 6-month follow-up measured by echocardiography. A total of 133 symptomatic HFrEF patients were included. The treatment was safe without any drug-related severe adverse events or difference in cardiac-related adverse events during a 3-year follow-up period. There were no significant differences between groups during follow-up in LVESV (0.3 ± 5.0 ml, p = 0.945), nor in secondary endpoints of left ventricular end-diastolic volume (-2.0 ± 6.0 ml, p = 0.736) and LVEF (-1.6 ± 1.0%, p = 0.119). The NYHA class improved slightly within the first year in both groups without any difference between groups. There were no changes in 6-min walk test, NT-proBNP, C-reactive protein or quality of life the first year in any groups. CONCLUSION: The SCIENCE trial demonstrated safety of intramyocardial allogeneic CSCC_ASC therapy in patients with chronic HFrEF. However, it was not possible to improve the pre-defined endpoints and induce restoration of cardiac function or clinical symptoms.

Microcirculatory Function in Nonhypertrophic and Hypertrophic Myocardium in Patients With Aortic Valve Stenosis.

Background Left ventricular hypertrophy (LVH) has often been supposed to be associated with abnormal myocardial blood flow and resistance. The aim of this study was to evaluate and quantify the physiological and pathological changes in myocardial blood flow and microcirculatory resistance in patients with and without LVH attributable to severe aortic stenosis. Methods and Results Absolute coronary blood flow and microvascular resistance were measured using a novel technique with continuous thermodilution and infusion of saline. In addition, myocardial mass was assessed with cardiac magnetic resonance imaging. Fifty-three patients with aortic valve stenosis were enrolled in the study. In 32 patients with LVH, hyperemic blood flow per gram of tissue was significantly decreased compared with 21 patients without LVH (1.26±0.48 versus 1.66±0.65 mL·min-1·g-1; P=0.018), whereas minimal resistance indexed for left ventricular mass was significantly increased in patients with LVH (63 [47-82] versus 43 [35-63] Wood Units·kg; P=0.014). Conclusions Patients with LVH attributable to severe aortic stenosis had lower hyperemic blood flow per gram of myocardium and higher minimal myocardial resistance compared with patients without LVH.

Outcome in Elderly Patients With Cardiogenic Shock Complicating Acute Myocardial Infarction.

INTRODUCTION: Despite advances in treatment of patients with cardiogenic shock following acute myocardial infarction (AMICS) in-hospital mortality remains around 50%. Outcome varies among patient subsets and the elderly often have a poor a priori prognosis. We sought to investigate outcome among elderly AMICS patients referred to evaluation and treatment at a tertiary university hospital. METHODS: Current analysis was based on the RETROSHOCK registry comprising consecutive AMICS patients admitted to tertiary care. Patients in the registry were individually identified and validated. RESULTS: Of 1,716 admitted patients, 496 (28.9%) patients were ≥75 years old. Older patients were less likely to be admitted directly to a tertiary centre (59.4% vs. 69.9%, P = 0.003), receive mechanical support devices (i.e., Impella® (8.9% vs. 15.0%, P = 0.003), and undergo revascularization attempt (76.8% vs. 90.2%, P < 0.001). Thirty-day survivors ≥75 years were characterized by having higher left ventricular ejection fraction (30.2% ±â€Š12.5% vs. 26.5% ±â€Š11.8%, P = 0.004) and lower arterial lactate (3.2[2.2-5.2] mmol/L vs. 5.5[3.3-8.2] mmol/L, P < 0.001) at admission. In a multivariable analysis of patients ≥75 years, higher age (HR 1.09, 95% CI 1.05-1.14, P < 0.001), higher heart rate (HR 1.01, 95% CI 1.001-1.014, P = 0.03), and higher lactate (HR 1.11, 95% CI 1.07-1.16, P < 0.001) at admission were associated with an increased risk of 30-day mortality. CONCLUSION: Among patients ≥75 years with AMICS referred for tertiary specialized treatment, 30-day mortality was 73.4%. Survivors were characterized by lower arterial lactate and heart rate at admission.

Long-Term Changes in Invasive Physiological Pressure Indices of Stenosis Severity Following Transcatheter Aortic Valve Implantation.

BACKGROUND: Patients with severe aortic stenosis frequently have coexisting coronary artery disease. Invasive hyperemic and nonhyperemic pressure indices are used to assess coronary artery disease severity but have not been evaluated in the context of severe aortic stenosis. METHODS: We compared lesion reclassification rates of fractional flow reserve (FFR) and resting full-cycle ratio (RFR) measured before and 6 months after transcatheter aortic valve implantation using the conventional clinical cutoffs of ≤0.80 for FFR and ≤0.89 for RFR. This was a substudy of the ongoing NOTION-3 trial (Third Nordic Aortic Valve Intervention). Two-dimensional quantitative coronary analysis was used to assess changes in angiographic lesion severity. RESULTS: Forty patients were included contributing 50 lesions in which FFR was measured. In 32 patients (36 lesions), RFR was also measured. There was no significant change in diameter stenosis from baseline to follow-up, 49.8% (42.9%-57.1%) versus 52.3% (43.2%-57.8%), P=0.50. RFR improved significantly from 0.88 (0.83%-0.93) at baseline to 0.92 (0.83-0.95) at follow-up, P=0.003, whereas FFR remained unchanged, 0.84 (0.81-0.89) versus 0.86 (0.78-0.90), P=0.72. At baseline, 11 out of 50 (22%) lesions were FFR-positive, whereas 15 out of 50 (30%) were positive at follow-up, P=0.219. Corresponding numbers for RFR were 23 out of 36 (64%) at baseline and 12 out of 36 (33%) at follow-up, P=0.003. CONCLUSIONS: In patients with severe aortic stenosis, physiological assessment of coronary lesions with FFR before transcatheter aortic valve implantation leads to lower reclassification rate at 6-month follow-up, compared with RFR.

Comparison of Effect of Ischemic Postconditioning on Cardiovascular Mortality in Patients With ST-Segment Elevation Myocardial Infarction Treated With Primary Percutaneous Coronary Intervention With Versus Without Thrombectomy.

In patients with ST-segment elevation myocardial infarction (STEMI), ischemic postconditioning (iPOST) have shown ambiguous results in minimizing reperfusion injury. Previous findings show beneficial effects of iPOST in patients with STEMI treated without thrombectomy. However, it remains unknown whether the cardioprotective effect of iPOST in these patients persist on long term. In the current study, all patients were identified through the DANAMI-3-iPOST database. Patients were randomized to conventional primary percutaneous coronary intervention (PCI) or iPOST in addition to PCI. Cumulative incidence rates were calculated, and multivariable analyses stratified according to thrombectomy use were performed. The primary end point was a combination of cardiovascular mortality and hospitalization for heart failure. From 2011 to 2014, 1,234 patients with STEMI were included with a median follow-up of 4.8 years. In patients treated without thrombectomy (n = 520), the primary end point occurred in 15% (48/326) in the iPOST group and in 22% (42/194) in the conventional group (unadjusted hazard ratio [HR] 0.62, 95% confidence interval [CI] 0.41 to 0.94, p = 0.023). In adjusted Cox analysis, iPOST remained associated with reduced long-term risk of cardiovascular mortality (HR 0.53, 95% CI 0.29 to 0.97, p = 0.039). In patients treated with thrombectomy (n = 714), there was no significant difference between iPOST (17%, 49/291) and conventional treatment (17%, 72/423) on the primary end point (unadjusted HR 1.01, 95% CI 0.70 to 1.45, p = 0.95). During a follow-up of nearly 5 years, iPOST reduced long-term occurrence of cardiovascular mortality and hospitalization for heart failure in patients with STEMI treated with PCI but without thrombectomy.

EAPCI Core Curriculum for Percutaneous Cardiovascular Interventions (2020): Committee for Education and Training European Association of Percutaneous Cardiovascular Interventions (EAPCI). A branch of the European Society of Cardiology.

The proposed 2020 Core Curriculum for Percutaneous Cardiovascular Interventions aims to provide an updated European consensus that defines the level of experience and knowledge in the field of percutaneous cardiovascular intervention (PCI). It promotes homogenous education and training programmes among countries, and is the cornerstone of the new EAPCI certification, designed to support the recognition of competencies at the European level and the free movement of certified specialists in the European Community. It is based on a thorough review of the ESC guidelines and of the EAPCI textbook on percutaneous interventional cardiovascular medicine. The structure of the current core curriculum evolved from previous EAPCI core curricula and from the "2013 core curriculum of the general cardiologist" to follow the current ESC recommendations for core curricula. In most subject areas, there was a wide - if not unanimous - consensus among the task force members on the training required for the interventional cardiologist of the future. The document recommends that acquisition of competence in interventional cardiology requires at least two years of postgraduate training, in addition to four years devoted to cardiology. The first part of the curriculum covers general aspects of training and is followed by a comprehensive description of the specific components in 54 chapters. Each of the chapters includes statements of the objectives, and is further subdivided into the required knowledge, skills, behaviours, and attitudes.

[Vascular endothelial growth factor therapy in ischaemic heart disease].

Atherosclerosis of coronary arteries can result in a hypoxic state where myocardial cells may become dysfunctional or die. The oxygen sensing transcription factor hypoxia inducible factor 1 responds to low oxygen levels by elevating the production of angiogenic growth factors, such as vascular endothelial growth factor (VEGF). Despite this, endogenous processes and conventional therapies are inefficient in some patients. To stimulate angiogenesis, VEGF has been injected into the myocardium. As stated in this review, this therapy has so far been proven safe and studies are conducted in several countries, including Denmark.

Jeopardized Myocardium and Survival in Patients Presenting to the Catheterization Laboratory With ST-Elevation Myocardial Infarction and Shock.

OBJECTIVE: We aimed to relate the amount of jeopardized myocardium to mortality in shocked patients presenting to the catheterization laboratory with ST-elevation myocardial infarction (STEMI) and cardiogenic shock. BACKGROUND: In contrast with historical data and previous professional guidance, contemporary randomized data suggest that multi-vessel revascularization in such patients does not improve survival; mechanistic insight is incomplete. METHODS: Clinical databases identified cases of STEMI and shock triaged for primary percutaneous coronary intervention (PPCI) in Eastern Denmark from June 2011 to December 2014 (n = 128). British Cardiovascular Intervention Society (BCIS)-1 jeopardy scores were calculated from angiography. The study endpoint was 30-day mortality. RESULTS: Median lactate values were 6.0 [2.9-10.7] mmol/L. 30-day mortality was 53.9%. 68% of patients had multi-vessel coronary disease. Median pre-PCI BCIS-1 myocardial jeopardy scores were 8 [6-10]. After multiple logistic regression increasing age (p = 0.008; odds ratio [OR] 1.06), lactate values (p = 0.017; OR 1.02), mechanical ventilation (p = 0.011; OR 1.25) and a systolic blood pressure ≤ 90 mmHg at end-case (p = 0.005; OR 1.26) were predictive of 30-day mortality. Post-PPCI culprit vessel TIMI 3 flow was associated with reduced mortality (p < 0.001; OR 0.66). There was no association between pre-PCI jeopardy scores and the primary endpoint. CONCLUSIONS: In patients with STEMI and shock, myocardial jeopardy scores do not relate to patient outcomes. Jeopardy scores may be applied to existing datasets in order to understand why multi-vessel revascularization does not lead to the anticipated clinical benefits in cardiogenic shock.

Interaction of ischaemic postconditioning and thrombectomy in patients with ST-elevation myocardial infarction.

OBJECTIVE: The Third Danish Study of Optimal Acute Treatment of Patients with ST-segment Elevation Myocardial Infarction - Ischaemic Postconditioning (DANAMI-3-iPOST) did not show improved clinical outcome in patients with ST-segment elevation myocardial infarction (STEMI) treated with ischaemic postconditioning. However, the use of thrombectomy was frequent and thrombectomy may in itself diminish the effect of ischaemic postconditioning. We evaluated the effect of ischaemic postconditioning in patients included in DANAMI-3-iPOST stratified by the use of thrombectomy. METHODS: Patients with STEMI were randomised to conventional primary percutaneous coronary intervention (PCI) or ischaemic postconditioning plus primary PCI. The primary endpoint was a combination of all-cause mortality and hospitalisation for heart failure. RESULTS: From March 2011 until February 2014, 1234 patients were included with a median follow-up period of 35 (interquartile range 28 to 42) months. There was a significant interaction between ischaemic postconditioning and thrombectomy on the primary endpoint (p=0.004). In patients not treated with thrombectomy (n=520), the primary endpoint occurred in 33 patients (10%) who underwent ischaemic postconditioning (n=326) and in 35 patients (18%) who underwent conventional treatment (n=194) (adjusted hazard ratio (HR) 0.55 (95%confidence interval (CI) 0.34 to 0.89), p=0.016). In patients treated with thrombectomy (n=714), there was no significant difference between patients treated with ischaemic postconditioning (n=291) and conventional PCI (n=423) on the primary endpoint (adjusted HR 1.18 (95% CI 0.62 to 2.28), p=0.62). CONCLUSIONS: In this post-hoc study of DANAMI-3-iPOST, ischaemic postconditioning, in addition to primary PCI, was associated with reduced risk of all-cause mortality and hospitalisation for heart failure in patients with STEMI not treated with thrombectomy. TRIAL REGISTRATION NUMBER: NCT01435408.

Vascular Positron Emission Tomography and Restenosis in Symptomatic Peripheral Arterial Disease: A Prospective Clinical Study.

OBJECTIVES: This study determined whether in vivo positron emission tomography (PET) of arterial inflammation (18F-fluorodeoxyglucose [18F-FDG]) or microcalcification (18F-sodium fluoride [18F-NaF]) could predict restenosis following PTA. BACKGROUND: Restenosis following lower limb percutaneous transluminal angioplasty (PTA) is common, unpredictable, and challenging to treat. Currently, it is impossible to predict which patient will suffer from restenosis following angioplasty. METHODS: In this prospective observational cohort study, 50 patients with symptomatic peripheral arterial disease underwent 18F-FDG and 18F-NaF PET/computed tomography (CT) imaging of the superficial femoral artery before and 6 weeks after angioplasty. The primary outcome was arterial restenosis at 12 months. RESULTS: Forty subjects completed the study protocol with 14 patients (35%) reaching the primary outcome of restenosis. The baseline activities of femoral arterial inflammation (18F-FDG tissue-to-background ratio [TBR] 2.43 [interquartile range (IQR): 2.29 to 2.61] vs. 1.63 [IQR: 1.52 to 1.78]; p < 0.001) and microcalcification (18F-NaF TBR 2.61 [IQR: 2.50 to 2.77] vs. 1.69 [IQR: 1.54 to 1.77]; p < 0.001) were higher in patients who developed restenosis. The predictive value of both 18F-FDG (cut-off TBRmax value of 1.98) and 18F-NaF (cut-off TBRmax value of 2.11) uptake demonstrated excellent discrimination in predicting 1-year restenosis (Kaplan Meier estimator, log-rank p < 0.001). CONCLUSIONS: Baseline and persistent femoral arterial inflammation and micro-calcification are associated with restenosis following lower limb PTA. For the first time, we describe a method of identifying complex metabolically active plaques and patients at risk of restenosis that has the potential to select patients for intervention and to serve as a biomarker to test novel interventions to prevent restenosis.