Factors associated with coronary angiography performed within 6 months of randomization to the conservative strategy in the ISCHEMIA Trial

BACKGROUND: ISCHEMIA (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) did not find an overall reduction in cardiovascular events with an initial invasive versus conservative management strategy in chronic coronary disease; however, there were conservative strategy participants who underwent invasive coronary angiography early postrandomization (within 6 months). Identifying factors associated with angiography in conservative strategy participants will inform clinical decision-making in patients with chronic coronary disease. METHODS: Factors independently associated with angiography performed within 6 months of randomization were identified using Fine and Gray proportional subdistribution hazard models, including demographics, region of randomization, medical history, risk factor control, symptoms, ischemia severity, coronary anatomy based on protocol-mandated coronary computed tomography angiography, and medication use. RESULTS: Among 2591 conservative strategy participants, angiography within 6 months of randomization occurred in 8.7% (4.7% for a suspected primary end point event, 1.6% for persistent symptoms, and 2.6% due to protocol nonadherence) and was associated with the following baseline characteristics: enrollment in Europe versus Asia (hazard ratio [HR], 1.81 [95% CI, 1.14­2.86]), daily and weekly versus no angina (HR, 5.97 [95% CI, 2.78­12.86] and 2.63 [95% CI, 1.51­4.58], respectively), poor to fair versus good to excellent health status (HR, 2.02 [95% CI, 1.23­3.32]) assessed with Seattle Angina Questionnaire, and new/more frequent angina prerandomization (HR, 1.80 [95% CI, 1.34­2.40]). Baseline low-density lipoprotein cholesterol <70 mg/dL was associated with a lower risk of angiography (HR, 0.65 [95% CI, 0.46­0.91) but not baseline ischemia severity nor the presence of multivessel or proximal left anterior descending artery stenosis >70% on coronary computed tomography angiography. CONCLUSIONS: Among ISCHEMIA participants randomized to the conservative strategy, angiography within 6 months of randomization was performed in <10% of patients. It was associated with frequent or increasing baseline angina and poor quality of life but not with objective markers of disease severity. Well-controlled baseline low-density lipoprotein cholesterol was associated with a reduced likelihood of angiography. These findings point to the importance of a comprehensive assessment of symptoms and a review of guideline-directed medical therapy goals when deciding the initial treatment strategy for chronic coronary disease.

Factors Associated With Coronary Angiography Performed Within 6 Months of Randomization to the Conservative Strategy in the ISCHEMIA Trial.

BACKGROUND: ISCHEMIA (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) did not find an overall reduction in cardiovascular events with an initial invasive versus conservative management strategy in chronic coronary disease; however, there were conservative strategy participants who underwent invasive coronary angiography early postrandomization (within 6 months). Identifying factors associated with angiography in conservative strategy participants will inform clinical decision-making in patients with chronic coronary disease. METHODS: Factors independently associated with angiography performed within 6 months of randomization were identified using Fine and Gray proportional subdistribution hazard models, including demographics, region of randomization, medical history, risk factor control, symptoms, ischemia severity, coronary anatomy based on protocol-mandated coronary computed tomography angiography, and medication use. RESULTS: Among 2591 conservative strategy participants, angiography within 6 months of randomization occurred in 8.7% (4.7% for a suspected primary end point event, 1.6% for persistent symptoms, and 2.6% due to protocol nonadherence) and was associated with the following baseline characteristics: enrollment in Europe versus Asia (hazard ratio [HR], 1.81 [95% CI, 1.14-2.86]), daily and weekly versus no angina (HR, 5.97 [95% CI, 2.78-12.86] and 2.63 [95% CI, 1.51-4.58], respectively), poor to fair versus good to excellent health status (HR, 2.02 [95% CI, 1.23-3.32]) assessed with Seattle Angina Questionnaire, and new/more frequent angina prerandomization (HR, 1.80 [95% CI, 1.34-2.40]). Baseline low-density lipoprotein cholesterol <70 mg/dL was associated with a lower risk of angiography (HR, 0.65 [95% CI, 0.46-0.91) but not baseline ischemia severity nor the presence of multivessel or proximal left anterior descending artery stenosis >70% on coronary computed tomography angiography. CONCLUSIONS: Among ISCHEMIA participants randomized to the conservative strategy, angiography within 6 months of randomization was performed in <10% of patients. It was associated with frequent or increasing baseline angina and poor quality of life but not with objective markers of disease severity. Well-controlled baseline low-density lipoprotein cholesterol was associated with a reduced likelihood of angiography. These findings point to the importance of a comprehensive assessment of symptoms and a review of guideline-directed medical therapy goals when deciding the initial treatment strategy for chronic coronary disease. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01471522.

Reintervention and Survival After Transcatheter Pulmonary Valve Replacement.

BACKGROUND: Transcatheter pulmonary valve (TPV) replacement (TPVR) has become the standard therapy for postoperative pulmonary outflow tract dysfunction in patients with a prosthetic conduit/valve, but there is limited information about risk factors for death or reintervention after this procedure. OBJECTIVES: This study sought to evaluate mid- and long-term outcomes after TPVR in a large multicenter cohort. METHODS: International registry focused on time-related outcomes after TPVR. RESULTS: Investigators submitted data for 2,476 patients who underwent TPVR and were followed up for 8,475 patient-years. A total of 95 patients died after TPVR, most commonly from heart failure (n = 24). The cumulative incidence of death was 8.9% (95% CI: 6.9%-11.5%) 8 years after TPVR. On multivariable analysis, age at TPVR (HR: 1.04 per year; 95% CI: 1.03-1.06 per year; P < 0.001), a prosthetic valve in other positions (HR: 2.1; 95% CI: 1.2-3.7; P = 0.014), and an existing transvenous pacemaker/implantable cardioverter-defibrillator (HR: 2.1; 95% CI: 1.3-3.4; P = 0.004) were associated with death. A total of 258 patients underwent TPV reintervention. At 8 years, the cumulative incidence of any TPV reintervention was 25.1% (95% CI: 21.8%-28.5%) and of surgical TPV reintervention was 14.4% (95% CI: 11.9%-17.2%). Risk factors for surgical reintervention included age (0.95 per year [95% CI: 0.93-0.97 per year]; P < 0.001), prior endocarditis (2.5 [95% CI: 1.4-4.3]; P = 0.001), TPVR into a stented bioprosthetic valve (1.7 [95% CI: 1.2-2.5]; P = 0.007), and postimplant gradient (1.4 per 10 mm Hg [95% CI: 1.2-1.7 per 10 mm Hg]: P < 0.001). CONCLUSIONS: These findings support the conclusion that survival and freedom from reintervention or surgery after TPVR are generally comparable to outcomes of surgical conduit/valve replacement across a wide age range.

Heterogeneity of diabetes as a risk factor for major adverse cardiovascular events in anticoagulated patients with atrial fibrillation: an analysis of the ARISTOTLE trial.

AIMS: Whether diabetes without insulin therapy is an independent cardiovascular (CV) risk factor in atrial fibrillation (AF) has recently been questioned. We investigated the prognostic relevance of diabetes with or without insulin treatment in patients in the ARISTOTLE trial. METHODS AND RESULTS: Patients with AF and increased stroke risk randomized to apixaban vs. warfarin were classified according to diabetes status: no diabetes; diabetes on no diabetes medications; diabetes on non-insulin antidiabetic drugs only; or insulin-treated. The associations between such patient subgroups and stroke/systemic embolism (SE), myocardial infarction (MI), and CV death were examined by Cox proportional hazard regression, both unadjusted and adjusted for other prognostic variables. Patients with diabetes were younger and had a higher body mass index. Median CHA2DS2VASc score was 4.0 in patients with diabetes and 3.0 in patients without diabetes. We found no significant difference in stroke/SE incidence across patient subgroups. Compared with no diabetes, only insulin-treated diabetes was significantly associated with higher risk. When adjusted for clinical variables, compared with no diabetes, the hazard ratios (HRs) for MI (95% confidence intervals) were for diabetes on no medication: 1.15 (0.62-2.14); for diabetes on non-insulin antidiabetic drugs: 1.32 (0.90-1.94); for insulin-treated diabetes: 2.34 (1.43-3.82); interaction P = 0.008. HRs for CV death were for diabetes on no medication: 1.19 (0.86-166); for diabetes on non-insulin antidiabetic drugs: 1.12 (0.88-1.42); for insulin-treated diabetes 1.85 (1.36-2.53), interaction P = 0.001. CONCLUSION: In anticoagulated patients with AF, a higher risk of MI and CV death is largely confined to diabetes treated with insulin.

Efficacy and safety of coronary computed tomography angiography in patients with a high clinical likelihood of obstructive coronary artery disease.

BACKGROUND: The CAT-CAD trial showed that coronary computed tomography angiography (CTA) in patients with a high prevalence of coronary artery disease (CAD) and indications for invasive coronary angiography (ICA) reduces the number of patients undergoing ICA by two-thirds and nearly eradicates non-actionable ICAs. However, the long-term benefits of this non-invasive strategy remain unknown. AIMS: To evaluate the long-term efficacy and safety of a non-invasive strategy employing coronary CTA vs. ICA as the first-line imaging test in stable patients with a high clinical likelihood of obstruc-tive CAD. METHODS: The long-term outcomes were evaluated for 36 months following randomization and included the efficacy outcome (analyzed as the composite of major adverse cardiovascular events (MACE): all-cause death, acute coronary syndrome, unplanned coronary revascularization, urgent hospitalization for a cardiovascular reason, a stroke) and the safety outcome (analyzed as a cumulative incidence of serious adverse events). RESULTS: One hundred and twenty participants at a mean age of 60.6 (7.9) years (female, 35.0%) were randomized with an allocation ratio of 1:1 to coronary CTA and direct ICA as the first-line anatomical test for suspected obstructive CAD. There were no significant differences between both diagnostic strategies neither in terms of the long-term efficacy (MACE occurrence: 15.5% in coronary CTA group vs. 16.7% in ICA group; log-rank P = 0.89) nor the long-term safety (cumulative number of serious adverse events: 36 vs. 38; P = 0.79, respectively). CONCLUSIONS: Long-term follow-up of the randomized CAT-CAD trial confirms that the strategy employing coronary CTA is an effective and safe, non-invasive, outpatient-based alternative to ICA for patients with a high clinical likelihood of obstructive CAD.

Optimal medical therapy in patients with stable coronary artery disease in Poland: the ISCHEMIA trial experience.

Introduction: Optimal medical therapy (OMT) is the cornerstone of treatment for stable coronary disease with the ISCHEMIA trial showing similar outcomes using OMT with or without an initial invasive approach. Objectives: To describe OMT goal attainment in Polish ISCHEMIA participants compared with other countries. Patients and methods: Among 5179 trial participants, 333 were randomized in Poland. The median follow-up was 3.2 years. OMT targets were: not smoking, high-intensity statin therapy, low-density lipoprotein cholesterol (LDL-C) of less than 70 mg/dl, systolic blood pressure of less than 140 mm Hg, aspirin therapy, and ACEI / ARB, and ß-blocker therapy if indicated. Results: Compared with 36 other countries, at randomization, patients in Poland were older (67 [62­75] y vs 65 [58­71] y); P <⁠0.001), more often female (30% vs 22%; P = 0.002), with a longer history of angina (3 [1­9] y vs 1 [0­3] y; P <⁠0.001), and there were more cases of prior myocardial infarction (32% vs 18%; P <⁠0.01) and revascularization (PCI, 40% vs 19%; CABG, 11% vs 3%; P <⁠0.001 for both). The number of OMT goals attained increased from baseline to follow-up visits (5 [4­5] vs 6 [5­6]; P <⁠0.001) in Poland and other countries alike (P = 0.89 vs P = 0.14). In Poland, significant improvements were achieved regarding high-intensity statin therapy (27% vs 50%), LDL-C <⁠70 mg/dl (29% vs 65%), and systolic blood pressure of less than 140 mm Hg (63% vs 81%) (P <⁠0.001 for all), whereas not-smoking (89% vs 89%), aspirin (90% vs 88%), ACEI / ARB (93% vs 95%), and ß-blocker therapy (94% vs 90%) remained high. Conclusions: With regular surveillance and contemporary medical therapy, high OMT goal attainment was achievable among the participants of the ISCHEMIA trial in Poland relative to other countries. There is still room for improvement in LDL-C and blood pressure management.

Comparison of myocardial tissue reperfusion of inferior wall and a right ventricle among patients after primary angioplasty for an inferior myocardial infarction with right ventricular infarction.

BACKGROUND: Impaired myocardial tissue reperfusion affects prognosis of patients with ST-segment elevation myocardial infarction (STEMI) treated with percutaneous coronary intervention (PCI) and can be identified by ST-segment analysis. To date, evaluation of the myocardial tissue reperfusion of the right ventricle (RV) among the patients treated with PCI for inferior STEMI with right ventricular infarction (RVI) has not been made yet. METHODS: Patients with inferior STEMI were screened for RVI. Tissue reperfusion was evaluated by maximal residual ST-segment deviation post PCI, independently for the RV and for inferior wall. Myocardial injury was assessed by the peak creatine kinase-mb (CK-MB) value. RESULTS: Among 456 patients with inferior STEMI, concomitant RVI occurred in 153 (33.5%) subjects (59.86±10.35 years old, 71.9% females). Tissue reperfusion of LV was present in 75 (49%), whereas 55 (35.9%) had both successful LV and RV reperfusion. Among 97 (63.4%) with successful tissue reperfusion of RV, 55 (56.7%) had associated successful tissue reperfusion of inferior wall. Adequate LV reperfusion was accompanied by RV in over 73.3% of patients (P=0.006). Mean peak CK-MB was lower in the group with adequate versus impaired RV tissue-perfusion (197±143 vs. 305±199 U/L, P=0.021 respectively). CONCLUSIONS: Impaired reperfusion of RV is observed in more than one third of inferior STEMIs with RVI and is not strictly associated with impaired reperfusion of inferior wall and clinical or angiographic variables, therefore ST-segment analysis for RV is mandatory.

Outcomes in non-ST-segment elevation myocardial infarction patients according to heart failure at admission: Insights from a large trial with systematic early invasive strategy.

BACKGROUND: Previous studies published before the era of systematic early invasive strategy have reported a higher mortality in non-ST-segment elevation myocardial infarction patients with heart failure. The aim of our study was to compare the clinical characteristics, outcomes and causes of death of patients according to their heart failure status at admission in a large non-ST-segment elevation myocardial infarction population with planned early invasive management. METHODS: We performed a post-hoc analysis of the Treatment of Acute Coronary Syndrome with Otamixaban randomised trial which included non-ST-segment elevation myocardial infarction patients with systematic coronary angiography within 72 h. Patients were categorised according to presence or absence of heart failure (Killip grade ≥2) at admission. RESULTS: A total of 13,172 patients were enrolled, of whom 944 (7.2%) had heart failure. At day 30, death occurred in 213 patients (1.6%) and cardiovascular death was the dominant cause of death in both groups ((with vs without heart failure) 78.8% vs 78.4%, p = 0.94). At six months, death occurred in 90/944 (9.5%) patients with heart failure and 258/12228 patients without heart failure (2.1%) (p < 0.001). After adjustment on Global Registry of Acute Coronary Events risk score, heart failure was an independent predictor of all-cause mortality at day 30 (odds ratio: 1.58; 95% confidence interval, 1.06-2.36, p = 0.02) and at day 180 (odds ratio: 1.77; 95% confidence interval, 1.3-2.42, p < 0.001) as well as of ischaemic complications (cardiovascular death, myocardial infarction, stent thrombosis or stroke at day 30 (odds ratio: 1.28; 95% confidence interval, 1.01-1.62, p = 0.04). CONCLUSION: Non-ST-segment elevation myocardial infarction patients with heart failure at admission still have worse outcomes than those without heart failure, even with systematic early invasive strategy. Further efforts are needed to improve the prognosis of these high risk patients.

Initial Invasive or Conservative Strategy for Stable Coronary Disease.

BACKGROUND: Among patients with stable coronary disease and moderate or severe ischemia, whether clinical outcomes are better in those who receive an invasive intervention plus medical therapy than in those who receive medical therapy alone is uncertain. METHODS: We randomly assigned 5179 patients with moderate or severe ischemia to an initial invasive strategy (angiography and revascularization when feasible) and medical therapy or to an initial conservative strategy of medical therapy alone and angiography if medical therapy failed. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. A key secondary outcome was death from cardiovascular causes or myocardial infarction. RESULTS: Over a median of 3.2 years, 318 primary outcome events occurred in the invasive-strategy group and 352 occurred in the conservative-strategy group. At 6 months, the cumulative event rate was 5.3% in the invasive-strategy group and 3.4% in the conservative-strategy group (difference, 1.9 percentage points; 95% confidence interval [CI], 0.8 to 3.0); at 5 years, the cumulative event rate was 16.4% and 18.2%, respectively (difference, -1.8 percentage points; 95% CI, -4.7 to 1.0). Results were similar with respect to the key secondary outcome. The incidence of the primary outcome was sensitive to the definition of myocardial infarction; a secondary analysis yielded more procedural myocardial infarctions of uncertain clinical importance. There were 145 deaths in the invasive-strategy group and 144 deaths in the conservative-strategy group (hazard ratio, 1.05; 95% CI, 0.83 to 1.32). CONCLUSIONS: Among patients with stable coronary disease and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of ischemic cardiovascular events or death from any cause over a median of 3.2 years. The trial findings were sensitive to the definition of myocardial infarction that was used. (Funded by the National Heart, Lung, and Blood Institute and others; ISCHEMIA ClinicalTrials.gov number, NCT01471522.).

Factors associated with the need for pulmonary valve replacement in asymptomatic patients with isolated pulmonary regurgitation after repair of tetralogy of Fallot: a cardiac magnetic resonance study.

BACKGROUND: Pulmonary regurgitation (PR) is the most common late complication in patients after repair of tetralogy of Fallot (TOF). Most patients remain asymptomatic over years, but eventually, the compensatory mechanisms fail, leading to right ventricular (RV) dilation and dysfunction, limited exercise capacity, ventricular arrhythmia, and sudden death. AIMS: We aimed to evaluate associations between cardiac magnetic resonance (CMR) parameters and the need for either surgical or percutaneous pulmonary valve replacement (PVR) in asymptomatic patients with significant PR after repair of TOF. METHODS: Of 209 patients with repaired TOF who had undergone a CMR study, we selected 61 asymptomatic patients with moderate­to­severe PR and followed them for up to 4 years (mean [SD], 21.4 [13.7] months). We excluded patients with residual ventricular septal defect, a peak RV outflow tract gradient of 30 mm Hg or higher, or at least moderate tricuspid regurgitation. RESULTS: Receiver operating characteristic curve analyses revealed that the ratio of RV to left ventricular (LV) volume (RV/ LV ratio; threshold >2.4) and PR fraction (PRF; threshold >33%) had acceptable discriminatory capacity to differentiate between patients requiring PVR and those treated conservatively. The Cox proportional hazards regression and the Kaplan­Meier curves revealed that the RV / LV ratio and PRF was significantly associated with the need for PVR. The combination of the RV / LV ratio and PRF provided significant discrimination in terms of survival without PVR (P <0.001; log­rank test for trend). CONCLUSIONS: The RV/ LV ratio and PRF were significantly associated with the need for PVR in asymptomatic patients with isolated moderate­to­severe PR after repair of TOF.

Transcatheter pulmonary valve implantation in 100 patients: a 10-year single-center experience.

Introduction: Transcatheter pulmonary valve implantation (TPVI) is a non-surgical method of treatment for patients with right ventricular outflow tract (RVOT) dysfunction after surgical repair of congenital heart defects (CHD). Aim: To evaluate the long-term results of TPVI performed in a single center.Material and methods: Over 10 years, TPVI was performed in 100 patients (mean age: 26.4 ±8.1 years), using Melody Medtronic or Sapien Edwards valves. Results: The initial success rate of TPVI was 93%. In 7 cases (5 urgent), a switch to surgical intervention was necessary due to periprocedural complications (all patients survived). Following TPVI, none of the 93 patients had severe pulmonary regurgitation. The pulmonary gradient decreased from 49.0 ±37.8 before to 27.6 ±14.9 mm Hg directly after TPVI (p < 0.0001). Right ventricular end-diastolic volume decreased, while NYHA class and pVO2 uptake significantly improved in 1 year after TPVI. Freedom from reintervention was 100% in 1 year. Freedom from serious adverse events was 86% in mean 5.5 years of observation. The main reason for reintervention was infective endocarditis (IE) (1.6% patients/year). Increased risk of IE was associated with severe PS before valve implantation and the suboptimal result of TPVI. The incidence of IE seems to be lower in patients treated permanently with antiplatelet therapy (1.8% vs. 0.9% patients/year, NS). Conclusions: TPVI is a safe and effective method of treatment in patients with RVOT dysfunction after surgical correction of CHD. To achieve a good outcome, precise patient selection and rigorous IE prevention are necessary.

Outcomes in non-ST-segment elevation myocardial infarction patients according to heart failure at admission: Insights from a large trial with systematic early invasive strategy.

BACKGROUND: Previous studies published before the era of systematic early invasive strategy have reported a higher mortality in non-ST-segment elevation myocardial infarction patients with heart failure. The aim of our study was to compare the clinical characteristics, outcomes and causes of death of patients according to their heart failure status at admission in a large non-ST-segment elevation myocardial infarction population with planned early invasive management. METHODS: We performed a post-hoc analysis of the Treatment of Acute Coronary Syndrome with Otamixaban randomised trial which included non-ST-segment elevation myocardial infarction patients with systematic coronary angiography within 72 h. Patients were categorised according to presence or absence of heart failure (Killip grade ≥2) at admission. RESULTS: A total of 13,172 patients were enrolled, of whom 944 (7.2%) had heart failure. At day 30, death occurred in 213 patients (1.6%) and cardiovascular death was the dominant cause of death in both groups ((with vs without heart failure) 78.8% vs 78.4%, p = 0.94). At six months, death occurred in 90/944 (9.5%) patients with heart failure and 258/12228 patients without heart failure (2.1%) (p < 0.001). After adjustment on Global Registry of Acute Coronary Events risk score, heart failure was an independent predictor of all-cause mortality at day 30 (odds ratio: 1.58; 95% confidence interval, 1.06-2.36, p = 0.02) and at day 180 (odds ratio: 1.77; 95% confidence interval, 1.3-2.42, p < 0.001) as well as of ischaemic complications (cardiovascular death, myocardial infarction, stent thrombosis or stroke at day 30 (odds ratio: 1.28; 95% confidence interval, 1.01-1.62, p = 0.04). CONCLUSION: Non-ST-segment elevation myocardial infarction patients with heart failure at admission still have worse outcomes than those without heart failure, even with systematic early invasive strategy. Further efforts are needed to improve the prognosis of these high risk patients.

Assessing the value of coronary artery computed tomography as the first-line anatomical test for stable patients with indications for invasive angiography due to suspected coronary artery disease. Initial cost analysis in the CAT-CAD randomized trial.

BACKGROUND: Clinical and safety outcomes of the strategy employing coronary computed tomography angiography (CCTA) as the first-choice imaging test have recently been demonstrated in the recently published CAT-CAD randomized, prospective, single-center study. Based on prospectively collected data in this patient population, we aimed to perform an initial cost analysis of this approach. METHODS: 120 participants of the CAT-CAD trial (age:60.6 ±â€¯7.9 years, 35% female) were included in the analysis. We analyzed medical resource use during the diagnostic and therapeutic episode of care. We prospectively estimated the cumulative cost for each strategy by multiplying the number of resources by standardized costs in accordance to medical databases and the 2015 Procedural Reimbursement Payment Guide. RESULTS: The total cost of coronary artery disease (CAD) diagnosis was significantly lower in the CCTA group as compared to the direct invasive coronary angiography (ICA) group ($50,176 vs $137,032) with corresponding per-patient cost of $836 vs $2,284, respectively. Similarly, the entire diagnostic and therapeutic episode of care was significantly less expensive in the CCTA group ($227,622 vs $502,827) with corresponding per-patient cost of $4630 vs $8,380, respectively. Overall, the application of CCTA as a first-line diagnostic test in stable patients with indications to ICA resulted in a 63% reduction of CAD diagnosis costs and a 55% reduction composite of diagnosis and treatment costs during 90-days follow-up. CONCLUSIONS: Application of CCTA as the first-line anatomic test in patients with suspected significant CAD decreased the total costs of diagnosis. This is likely attributable to reduced numbers of invasive tests and hospitalisations. Initial cost analysis of the CAT-CAD randomized trial suggests that this approach may provide significant cost savings for the entire health system.

Successful primary percutaneous coronary intervention determines the very long-term prognosis in ST-segment elevation myocardial infarction even in survivors of the acute phase. The ANIN Myocardial Infarction Registry.

INTRODUCTION: Successful primary percutaneous coronary intervention (pPCI) saves lives in the acute phase of ST-elevation myocardial infarction (STEMI) and improves the mid-term prognosis. Whether that benefit remains significant in very long-term follow-up and is associated with total ischaemic time (TIT), especially in survivors of the acute phase of STEMI, is unknown. AIM: We sought to investigate the impact of initial and final thrombolysis in myocardial infarction (TIMI) flow on long-term survival in a homogeneous, unselected group of patients with STEMI undergoing pPCI at a high-volume centre. MATERIAL AND METHODS: All consecutive STEMI patients treated with pPCI in our tertiary centre were enrolled in the ANIN Myocardial Infarction Registry. RESULTS: Among 1064 patients 871 (82%) had an occluded infarct artery (IRA) at baseline, while pPCI was successful in 885 (83%) patients. At 9 years all-cause and cardiovascular (CV) mortality were 28% (294 patients) and 19% (196 patients), respectively. Failure of pPCI was an independent predictor of long-term all-cause and CV mortality (OR = 1.5, 95% CI: 1.1-2.0, p = 0.03 and OR = 1.8, 95% CI: 1.3-2.7, p = 0.001, respectively). In survivors of the acute phase, occluded IRA at baseline was an independent predictor of all-cause mortality (OR = 1.5, 95% CI: 1.0-2.3, p = 0.04), while pPCI failure predicted CV mortality (OR = 1.8, 95% CI: 1.2-2.8, p = 0.005). Mortality rate increased with TIT even in patients with pPCI success. CONCLUSIONS: Angiographic results of pPCI determine the very long-term survival of STEMI patients, even in survivors of the acute phase of STEMI. Shortening of TIT is crucial.

The natural history of napkin-ring sign by coronary computed tomography angiography.

INTRODUCTION: Despite their significance, the prevalence and the incidence of vulnerable plaques in coronary arteries, as well as their natural history, remain poorly known. AIM: To evaluate the prevalence, incidence and evolution of napkin-ring sign (NRS), and to establish factors associated with its presence, progression, or regression, in patients with suspected coronary artery disease (CAD). MATERIAL AND METHODS: The study is based on a single-center prospective registry. Eighty-nine patients with suspected CAD underwent two computed tomography angiography (CTA) examinations within an interval of at least 24 months. High-risk plaque was defined by the presence of a low-attenuation area adjacent to the coronary lumen, surrounded by a ring of higher attenuation - NRS. RESULTS: At the baseline 53 NRS were observed in 22 (25%) patients, 7 (8%) patients had single NRS and 15 (17%) had multiple NRS. After the follow-up period, there were 68 NRS in 32 patients. In 18 patients progression was observed with 23 additional NRS. Presence of single NRS and diabetes were independent predictors of NRS progression. CONCLUSIONS: The number of NRS plaque tends to increase over time in patients with suspected CAD. The progression may be predicted by the presence of diabetes or single NRS.

Long-term follow-up and safety assessment of angiogenic gene therapy trial VIF-CAD: Transcatheter intramyocardial administration of a bicistronic plasmid expressing VEGF-A165/bFGF cDNA for the treatment of refractory coronary artery disease.

There have been a number of angiogenic gene therapy trials, yielding mixed results as to efficacy, but demonstrating uniform short-term treatment safety. Data regarding long-term safety of angiogenic gene therapy are limited. Double-blind VIF-CAD trial (NCT00620217) assessed myocardial perfusion and clinical data in 52 refractory coronary artery disease (CAD) patients randomized into treatment (VIF; n = 33) and Placebo (n = 19) arms. VIF group received electromechanical system NOGA-guided intramyocardial injections of VEGF-A165/bFGF plasmid (VIF) into ischemic regions, while the Placebo group-placebo plasmid injections. Full 1-year follow-up data have been published. This study presents the results of over 10-year (median 133 months, range 95-149) safety follow-up of VIF-CAD patients. Overall, 12 (36.4%) patients died in VIF and 8 (42.1%) in Placebo group (P = .68). Cardiovascular mortality was 12/33 (36.4%) in the VIF group and 6/19 (31.6%) in Placebo group (P = .73). Two Placebo patients died due to malignancies, but no VIF patients (P = .17). The Kaplan-Meier curves of combined endpoint: cardiovascular mortality, myocardial infarction and stroke were similar for both patient groups (P = .71). Odds ratio of Placebo group increasing (reaching a worse) their CCS class versus VIF was non-significant (OR 1.28, 95% CI = 0.66-2.45; P = .47). However, CCS class improved in time irrespectively of treatment-OR of reaching a less favorable CCS class per each year of follow-up was 0.74 (95% CI 0.685-0.792; P < .0001, pooled data). There were no differences in readmission rates. Intramyocardial VEGF-A165/bFGF plasmid administration appears safe, with no evidence of an increase in the incidence of death, malignancy, myocardial infarction or stroke during 10-year follow-up in this limited patient population.