Association of growth and differentiation factor-15 with coronary artery calcium score and ankle-brachial index in a middle-aged and elderly Caucasian population sample free of manifest cardiovascular disease.

Growth and differentiation factor-15 (GDF-15) is a stress-associated cytokine of the transforming growth factor-ß superfamily. The inflammatory and angiogenic effects of GDF-15 in atherosclerosis are controversial, and its correlation with the long asymptomatic phase of the disease is not well understood. Coronary artery calcium score (CACS) and ankle-brachial index (ABI) are sensitive markers of subclinical atherosclerosis. To date, only a few studies have examined the impact of GDF-15 on coronary artery calcification, and the association between GDF-15 and ABI has not been evaluated. Therefore, we aimed to investigate the possible relationship between serum GDF-15 concentrations and CACS and ABI in a Caucasian population sample of middle-aged (35-65 years) and elderly (> 65 years) people. In addition to recording demographic and anthropometric characteristics, atherosclerotic risk factors, and laboratory tests including serum HDL-cholesterol, LDL-cholesterol, hemoglobin A1c (HbA1c), high-sensitivity C-reactive protein, and N-terminal pro-B-type natriuretic peptide (NT-proBNP); GDF-15 level, cardiac computed tomography, and ABI measurements were also performed. A total of 269 asymptomatic individuals (men, n = 125; median age, 61.5 [IQR, 12.7] years) formed the basis of this study. Participants were divided into two groups according to their age (middle-aged, n = 175 and elderly, n = 94). Hypertension and diabetes mellitus were significantly more prevalent and CACS values and HbA1c, NT-proBNP, and GDF-15 levels were significantly higher (all p < 0.001) in the elderly group compared to the middle-aged group. Multivariate ridge regression analysis revealed a significant positive association between GDF-15 and CACS (middle-aged group: ß = 0.072, p = 0.333; elderly group: ß = 0.148, p = 0.003), and between GDF-15 and ABI (middle-aged group: ß = 0.062, p = 0.393; elderly group: ß = 0.088, p = 0.041) only in the elderly group. Our results show that GDF-15 is not only a useful biomarker of inflammation but can also predict early signs of asymptomatic atherosclerosis, especially in elderly people with chronic systemic inflammation associated with aging (inflammaging).

Neutrophil-to-Lymphocyte Ratio Is an Independent Risk Factor for Coronary Artery Disease in Central Obesity.

Several inflammatory biomarkers were found to be associated with an increased risk of cardiovascular disease. Neutrophil-to-lymphocyte ratio (NLR) is a marker of subclinical inflammation that increases with the stress response. Visceral adiposity index (VAI) calculated as a combination of anthropometric and metabolic parameters reflects both the extent and function of visceral adipose tissue. Given the association of subclinical inflammation with both obesity and cardiovascular diseases, it is plausible that the inflammation-CVD association is modulated by the amount and function of adipose tissue. Thus, our aim was to examine the association between NLR and coronary artery calcium score (CACS), an intermediate marker of coronary artery disease in asymptomatic patients across VAI tertiles. Methods: Data from 280 asymptomatic participants of a cardiovascular screening program were analysed. In addition to the collection of lifestyle and medical history, a non-contrast cardiac CT scan and laboratory tests were performed on all participants. Multivariate logistic regression was conducted with CACS > 100 as the outcome and with conventional cardiovascular risk factors and NLR, VAI, and NLR by VAI tertile as predictors. Results: We found an interaction between VAI tertiles and NLR; NLR values were similar in the lower VAI tertiles, while they were higher in the CACS > 100 in the 3rd VAI tertile (CACS ≤ 100: 1.94 ± 0.58 vs. CACS > 100: 2.48 ± 1.1, p = 0.008). According to multivariable logistic regression, the interaction between NLR and VAI tertiles remained: NLR was associated with CACS > 100 in the 3rd VAI tertile (OR = 1.67, 95% CI 1.06-2.62, p = 0.03) but not in the lower tertiles even after adjustment for age, sex, smoking, history of hypertension, hyperlipidaemia, and diabetes mellitus, as well as high-sensitivity C-reactive protein. Our findings draw attention to the independent association between subclinical, chronic, systemic inflammation and subclinical coronary disease in obesity.

Impact of chronic obstructive pulmonary disease on short-term outcome in patients with ST-elevation myocardial infarction during COVID-19 pandemic: insights from the international multicenter ISACS-STEMI registry.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is projected to become the third cause of mortality worldwide. COPD shares several pathophysiological mechanisms with cardiovascular disease, especially atherosclerosis. However, no definite answers are available on the prognostic role of COPD in the setting of ST elevation myocardial infarction (STEMI), especially during COVID-19 pandemic, among patients undergoing primary angioplasty, that is therefore the aim of the current study. METHODS: In the ISACS-STEMI COVID-19 registry we included retrospectively patients with STEMI treated with primary percutaneous coronary intervention (PCI) between March and June of 2019 and 2020 from 109 high-volume primary PCI centers in 4 continents. RESULTS: A total of 15,686 patients were included in this analysis. Of them, 810 (5.2%) subjects had a COPD diagnosis. They were more often elderly and with a more pronounced cardiovascular risk profile. No preminent procedural dissimilarities were noticed except for a lower proportion of dual antiplatelet therapy at discharge among COPD patients (98.9% vs. 98.1%, P = 0.038). With regards to short-term fatal outcomes, both in-hospital and 30-days mortality occurred more frequently among COPD patients, similarly in pre-COVID-19 and COVID-19 era. However, after adjustment for main baseline differences, COPD did not result as independent predictor for in-hospital death (adjusted OR [95% CI] = 0.913[0.658-1.266], P = 0.585) nor for 30-days mortality (adjusted OR [95% CI] = 0.850 [0.620-1.164], P = 0.310). No significant differences were detected in terms of SARS-CoV-2 positivity between the two groups. CONCLUSION: This is one of the largest studies investigating characteristics and outcome of COPD patients with STEMI undergoing primary angioplasty, especially during COVID pandemic. COPD was associated with significantly higher rates of in-hospital and 30-days mortality. However, this association disappeared after adjustment for baseline characteristics. Furthermore, COPD did not significantly affect SARS-CoV-2 positivity. TRIAL REGISTRATION NUMBER: NCT04412655 (2nd June 2020).

Iliofemoral Tortuosity Increases the Risk of Access-Site-Related Complications After Aortic Valve Implantation and Plug-Based Access-Site Closure.

Background: Access-site-related complications are often related to high-risk anatomy and technical pitfalls and impair the outcomes of transfemoral aortic valve implantations (TAVIs). Calcification and tortuosity are widely recognized risk factors, and their impact on procedural planning is left to the implanting experts' discretion. To facilitate decision-making, we introduced a quantitative measure for iliofemoral tortuosity and assessed its predictive value for access-site-related vascular and bleeding complications. Methods: We performed a single-centre prospective cohort study of consecutive, percutaneous transfemoral TAVI performed between April 2019 and March 2020. Medical history and all-cause mortality were extracted from the electronic patient files. Arterial anatomy and calcifications were evaluated using 3mensio Structural Heart software. The primary outcome was access-site-related vascular or bleeding complications. Results: In this elderly, intermediate-risk population, we registered the primary outcome in 43 patients (39%), and major access-site complications in 10 patients (9.2%). Complete hemostasis was achieved in 77 patients (70.6%), by the application of the MANTA plug alone. In the group with access-site-related adverse events, compared with the group without, the tortuosity index was higher median (26% interquartile range [IQR 18%-33%] vs median 19% [IQR 13%-29%], respectively; P = 0.012), as was maximal angulation median (50° [IQR 40°-59°] vs median 43° [IQR 36°-51°], respectively; P = 0.026) were higher. Both variables had a significant effect on our primary outcome, with odds ratios (OR) of 3.1 (tortuosity, P = 0.005) and 2.6 (angulation, P = 0.020). The degree of angulation was a predictor of major complications too (odds ratio 7 [1.4-34.8]; P = 0.017). Conclusions: Steeper angles and greater arterial elongation increase the risk of vascular and bleeding complications after femoral TAVI with the utilization of a plug-based closure device.

Introduction: Les complications liées au site d'accès qui sont souvent associées à une anatomie qui expose à des risques élevés et aux pièges techniques nuisent aux résultats cliniques des implantations valvulaires aortiques par cathéter (TAVI) par voie fémorale. Il est largement reconnu que la calcification et la tortuosité sont des facteurs de risque. Par conséquent, leurs conséquences sur la planification interventionnelle sont laissées à la discrétion des experts en implantation. Pour faciliter la prise de décision, nous avons mis en place une mesure quantitative de tortuosités iliofémorales et évalué sa valeur prédictive sur la survenue de complications vasculaires et hémorragiques liées au site d'accès. Méthodes: Nous avons réalisé une étude de cohorte prospective unicentrique de TAVI percutanées par voie fémorale consécutives effectuées entre avril 2019 et mars 2020. Nous avons extrait les antécédents médicaux et la mortalité toutes causes confondues des dossiers médicaux électroniques. Nous avons évalué l'anatomie artérielle et les calcifications à l'aide du logiciel 3mensio Structural Heart. Le critère de jugement principal était les complications vasculaires ou hémorragiques liées au site d'accès. Résultats: Dans cette population âgée exposée à un risque intermédiaire, nous avons enregistré le critère de jugement principal de 43 patients (39 %), et les principales complications du site d'accès de 10 patients (9,2 %). Soixante-dix-sept patients (70,6 %) ont obtenu l'hémostase complète par la seule application du bouchon MANTA. L'indice de tortuosité était plus élevé dans le groupe qui avait subi des événements défavorables liés au site d'accès que dans le groupe qui n'avait pas subi d'événements défavorables (26 % [18 %-33 %] vs 19 % [13 %-29 %], respectivement; P = 0,012). Il en était de même pour l'angulation maximale (50° [40°-59°] vs 43° [36°-51°], respectivement; P = 0,026) qui était plus grande. Les deux variables ont eu des effets significatifs sur le critère de jugement principal, soit des rapports de cotes (RC) de 3,1 (tortuosité, P = 0,005) et de 2,6 (angulation, P = 0,020). Le degré d'angulation était aussi un prédicteur de complications majeures (rapport de cotes 7 [1,4-34,8]; P = 0,017). Conclusions: Des angles plus prononcés et une plus grande élongation des artères augmentent le risque de complications vasculaires et hémorragiques après la TAVI par voie fémorale lors de l'utilisation d'un dispositif de fermeture à bouchon.

COVID-19 pandemic, mechanical reperfusion and 30-day mortality in ST elevation myocardial infarction.

OBJECTIVE: The initial data of the International Study on Acute Coronary Syndromes - ST Elevation Myocardial Infarction COVID-19 showed in Europe a remarkable reduction in primary percutaneous coronary intervention procedures and higher in-hospital mortality during the initial phase of the pandemic as compared with the prepandemic period. The aim of the current study was to provide the final results of the registry, subsequently extended outside Europe with a larger inclusion period (up to June 2020) and longer follow-up (up to 30 days). METHODS: This is a retrospective multicentre registry in 109 high-volume primary percutaneous coronary intervention (PPCI) centres from Europe, Latin America, South-East Asia and North Africa, enrolling 16 674 patients with ST segment elevation myocardial infarction (STEMI) undergoing PPPCI in March/June 2019 and 2020. The main study outcomes were the incidence of PPCI, delayed treatment (ischaemia time >12 hours and door-to-balloon >30 min), in-hospital and 30-day mortality. RESULTS: In 2020, during the pandemic, there was a significant reduction in PPCI as compared with 2019 (incidence rate ratio 0.843, 95% CI 0.825 to 0.861, p<0.0001). This reduction was significantly associated with age, being higher in older adults (>75 years) (p=0.015), and was not related to the peak of cases or deaths due to COVID-19. The heterogeneity among centres was high (p<0.001). Furthermore, the pandemic was associated with a significant increase in door-to-balloon time (40 (25-70) min vs 40 (25-64) min, p=0.01) and total ischaemia time (225 (135-410) min vs 196 (120-355) min, p<0.001), which may have contributed to the higher in-hospital (6.5% vs 5.3%, p<0.001) and 30-day (8% vs 6.5%, p=0.001) mortality observed during the pandemic. CONCLUSION: Percutaneous revascularisation for STEMI was significantly affected by the COVID-19 pandemic, with a 16% reduction in PPCI procedures, especially among older patients (about 20%), and longer delays to treatment, which may have contributed to the increased in-hospital and 30-day mortality during the pandemic. TRIAL REGISTRATION NUMBER: NCT04412655.

Urgent transcatheter aortic valve implantation in an all-comer population: a single-centre experience.

BACKGROUND: When compared with older reports of untreated symptomatic aortic valve stenosis (AoS), urgent transcatheter aortic valve implantation (u-TAVI) seems to improve mortality rates. We performed a single centre, retrospective cohort analysis to characterize our u-TAVI population and to identify potential predictors of worse outcomes. METHODS: We performed a retrospective analysis of 631 consecutive TAVI patients between 2013 and 2018. Of these patients, 53 were categorized as u-TAVI. Data was collected from the local electronic database. RESULTS: Urgent patients had more often a severely decreased left ventricular ejection fraction (LVEF < 30%) and increased creatinine levels (115.5 [88-147] vs 94.5 [78-116] mmol/l; p = 0.001). Urgent patients were hospitalised for 18 [10-28] days before and discharged 6 [4-9] days after the implantation. The incidence of peri-procedural complications and apical implantations was comparable among the study groups. Urgent patients had higher in-hospital (11.3% vs 3.1%; p = 0.011) and 1-year mortality rates (28.2% vs 8.5%, p < 0.001). An increased risk of one-year mortality was associated with urgency (HR 3.5; p < 0.001), apical access (HR 1.9; p = 0.016) and cerebrovascular complications (HR 4.3; p = 0.002). Within the urgent group, the length of pre-hospital admission was the only significant predictor of 1-year mortality (HR 1.037/day; p = 0.003). CONCLUSIONS: Compared to elective procedures, u-TAVI led to increased mortality and comparable complication rates. This detrimental effect is most likely related to the length of pre-procedural hospitalisation of urgent patients.

Impact of renin-angiotensin system inhibitors on mortality during the COVID Pandemic among STEMI patients undergoing mechanical reperfusion: Insight from an international STEMI registry.

BACKGROUND: Concerns have been raised on a potential interaction between renin-angiotensin system inhibitors (RASI) and the susceptibility to coronavirus disease 2019 (COVID-19). No data have been so far reported on the prognostic impact of RASI in patients suffering from ST-elevation myocardial infarction (STEMI) during COVID-19 pandemic, which was the aim of the present study. METHODS: STEMI patients treated with primary percutaneous coronary intervention (PPCI) and enrolled in the ISACS-STEMI COVID-19 registry were included in the present sub-analysis and divided according to RASI therapy at admission. RESULTS: Our population is represented by 6095 patients, of whom 3654 admitted in 2019 and 2441 in 2020. No difference in the prevalence of SARSCoV2 infection was observed according to RASI therapy at admission (2.5% vs 2.1%, p = 0.5), which was associated with a significantly lower mortality (adjusted OR [95% CI]=0.68 [0.51-0.90], P = 0.006), confirmed in the analysis restricted to 2020 (adjusted OR [95% CI]=0.5[0.33-0.74], P = 0.001). Among the 5388 patients in whom data on in-hospital medication were available, in-hospital RASI therapy was associated with a significantly lower mortality (2.1% vs 16.7%, OR [95% CI]=0.11 [0.084-0.14], p < 0.0001), confirmed after adjustment in both periods. Among the 62 SARSCoV-2 positive patients, RASI therapy, both at admission or in-hospital, showed no prognostic effect. CONCLUSIONS: This is the first study to investigate the impact of RASI therapy on the prognosis and SARSCoV2 infection of STEMI patients undergoing PPCI during the COVID-19 pandemic. Both pre-admission and in-hospital RASI were associated with lower mortality. Among SARSCoV2-positive patients, both chronic and in-hospital RASI therapy showed no impact on survival.

Renin-angiotensin system inhibitors and mortality among diabetic patients with STEMI undergoing mechanical reperfusion during the COVID-19 pandemic.

BACKGROUND: During the coronavirus disease 2019 (COVID-19) pandemic, concerns have been arisen on the use of renin-angiotensin system inhibitors (RASI) due to the potentially increased expression of Angiotensin-converting-enzyme (ACE)2 and patient's susceptibility to SARS-CoV2 infection. Diabetes mellitus have been recognized favoring the coronavirus infection with consequent increase mortality in COVID-19. No data have been so far reported in diabetic patients suffering from ST-elevation myocardial infarction (STEMI), a very high-risk population deserving of RASI treatment. METHODS: The ISACS-STEMI COVID-19 registry retrospectively assessed STEMI patients treated with primary percutaneous coronary intervention (PPCI) in March/June 2019 and 2020 in 109 European high-volume primary PCI centers. This subanalysis assessed the prognostic impact of chronic RASI therapy at admission on mortality and SARS-CoV2 infection among diabetic patients. RESULTS: Our population is represented by 3812 diabetic STEMI patients undergoing mechanical reperfusion, 2038 in 2019 and 1774 in 2020. Among 3761 patients with available data on chronic RASI therapy, between those ones with and without treatment there were several differences in baseline characteristics, (similar in both periods) but no difference in the prevalence of SARS-CoV2 infection (1.6% vs 1.3%, respectively, p = 0.786). Considering in-hospital medication, RASI therapy was overall associated with a significantly lower in-hospital mortality (3.3% vs 15.8%, p < 0.0001), consistently both in 2019 and in 2010. CONCLUSIONS: This is first study to investigate the impact of RASI therapy on prognosis and SARS-CoV2 infection of diabetic patients experiencing STEMI and undergoing PPCI during the COVID-19 pandemic. Both pre-admission chronic RASI therapy and in-hospital RASI did not negatively affected patients' survival during the hospitalization, neither increased the risk of SARS-CoV2 infection. TRIAL REGISTRATION NUMBER: NCT04412655.

Impact of COVID-19 pandemic and diabetes on mechanical reperfusion in patients with STEMI: insights from the ISACS STEMI COVID 19 Registry.

BACKGROUND: It has been suggested the COVID pandemic may have indirectly affected the treatment and outcome of STEMI patients, by avoidance or significant delays in contacting the emergency system. No data have been reported on the impact of diabetes on treatment and outcome of STEMI patients, that was therefore the aim of the current subanalysis conducted in patients included in the International Study on Acute Coronary Syndromes-ST Elevation Myocardial Infarction (ISACS-STEMI) COVID-19. METHODS: The ISACS-STEMI COVID-19 is a retrospective registry performed in European centers with an annual volume of > 120 primary percutaneous coronary intervention (PCI) and assessed STEMI patients, treated with primary PCI during the same periods of the years 2019 versus 2020 (March and April). Main outcomes are the incidences of primary PCI, delayed treatment, and in-hospital mortality. RESULTS: A total of 6609 patients underwent primary PCI in 77 centers, located in 18 countries. Diabetes was observed in a total of 1356 patients (20.5%), with similar proportion between 2019 and 2020. During the pandemic, there was a significant reduction in primary PCI as compared to 2019, similar in both patients with (Incidence rate ratio (IRR) 0.79 (95% CI: 0.73-0.85, p < 0.0001) and without diabetes (IRR 0.81 (95% CI: 0.78-0.85, p < 0.0001) (p int = 0.40). We observed a significant heterogeneity among centers in the population with and without diabetes (p < 0.001, respectively). The heterogeneity among centers was not related to the incidence of death due to COVID-19 in both groups of patients. Interaction was observed for Hypertension (p = 0.024) only in absence of diabetes. Furthermore, the pandemic was independently associated with a significant increase in door-to-balloon and total ischemia times only among patients without diabetes, which may have contributed to the higher mortality, during the pandemic, observed in this group of patients. CONCLUSIONS: The COVID-19 pandemic had a significant impact on the treatment of patients with STEMI, with a similar reduction in primary PCI procedures in both patients with and without diabetes. Hypertension had a significant impact on PCI reduction only among patients without diabetes. We observed a significant increase in ischemia time and door-to-balloon time mainly in absence of diabetes, that contributed to explain the increased mortality observed in this group of patients during the pandemic. TRIAL REGISTRATION NUMBER: NCT04412655.

Impact of COVID-19 Pandemic on Mechanical Reperfusion for Patients With STEMI.

BACKGROUND: The fear of contagion during the coronavirus disease-2019 (COVID-19) pandemic may have potentially refrained patients with ST-segment elevation myocardial infarction (STEMI) from accessing the emergency system, with subsequent impact on mortality. OBJECTIVES: The ISACS-STEMI COVID-19 registry aims to estimate the true impact of the COVID-19 pandemic on the treatment and outcome of patients with STEMI treated by primary percutaneous coronary intervention (PPCI), with identification of "at-risk" patient cohorts for failure to present or delays to treatment. METHODS: This retrospective registry was performed in European high-volume PPCI centers and assessed patients with STEMI treated with PPPCI in March/April 2019 and 2020. Main outcomes are the incidences of PPCI, delayed treatment, and in-hospital mortality. RESULTS: A total of 6,609 patients underwent PPCI in 77 centers, located in 18 countries. In 2020, during the pandemic, there was a significant reduction in PPCI as compared with 2019 (incidence rate ratio: 0.811; 95% confidence interval: 0.78 to 0.84; p < 0.0001). The heterogeneity among centers was not related to the incidence of death due to COVID-19. A significant interaction was observed for patients with arterial hypertension, who were less frequently admitted in 2020 than in 2019. Furthermore, the pandemic was associated with a significant increase in door-to-balloon and total ischemia times, which may have contributed to the higher mortality during the pandemic. CONCLUSIONS: The COVID-19 pandemic had significant impact on the treatment of patients with STEMI, with a 19% reduction in PPCI procedures, especially among patients suffering from hypertension, and a longer delay to treatment, which may have contributed to the increased mortality during the pandemic. (Primary Angioplasty for STEMI During COVID-19 Pandemic [ISACS-STEMI COVID-19] Registry; NCT04412655).

Association between coronary atherosclerosis and visceral adiposity index.

BACKGROUND AND AIMS: Visceral obesity is a marker of dysfunctional adipose tissue and ectopic fat infiltration. Many studies have shown that visceral fat dysfunction has a close relationship with cardiovascular disease. For a better identification of visceral adiposity dysfunction, the visceral adiposity index (VAI) is used. Coronary artery calcium score (CACS) is known to have a strong correlation with the total plaque burden therefore provides information about the severity of the coronary atherosclerosis. CACS is a strong predictor of cardiac events and it refines cardiovascular risk assessment beyond conventional risk factors. Our aim was to evaluate the association between VAI and CACS in an asymptomatic Caucasian population. METHODS AND RESULTS: Computed tomography scans of 460 participants were analyzed in a cross-sectional, voluntary screening program. A health questionnaire, physical examination and laboratory tests were also performed. Participants with a history of cardiovascular disease were excluded from the analysis. Mean VAI was 1.41 ± 0.07 in men and 2.00 ± 0.15 in women. VAI showed a positive correlation with total coronary calcium score (r = 0.242) in males but not in females. VAI was stratified into tertiles by gender. In males, third VAI tertile was independently associated with CACS>100 (OR: 3.21, p = 0.02) but not with CACS>0 after the effects of conventional risk factors were eliminated. CONCLUSION: VAI tertiles were associated with calcium scores and the highest VAI tertile was an independent predictor for the presence of CACS>100 in males but not in females.

Characterization of the dynamic changes in left ventricular morphology and function induced by exercise training and detraining.

BACKGROUND: Although exercise-induced cardiac hypertrophy has been intensively investigated, its development and regression dynamics have not been comprehensively described. In the current study, we aimed to characterize the effects of regular exercise training and detraining on left ventricular (LV) morphology and function. METHODS: Rats were divided into exercised (n = 12) and control (n = 12) groups. Exercised rats swam 200 min/day for 12 weeks. After completion of the training protocol, rats remained sedentary for 8 weeks (detraining period). Echocardiographic follow-up was performed regularly to obtain LV long- and short-axis recordings for speckle-tracking echocardiography analysis. Global longitudinal and circumferential strain and systolic strain rate were measured. LV pressure-volume analysis was performed using additional groups of rats to obtain haemodynamic data. RESULTS: Echocardiographic examinations showed the development of LV hypertrophy in the exercised group. These differences disappeared during the detraining period. Strain and strain rate values were all increased after the training period, whereas supernormal values rapidly reversed to the control level after training cessation. Load-independent haemodynamic indices, e.g., preload recruitable stroke work, confirmed the exercise-induced systolic improvement and complete regression after detraining. CONCLUSIONS AND TRANSLATIONAL ASPECT: Our results provide the first comprehensive data to describe the development and regression dynamics of morphological and functional aspects of physiological hypertrophy in detail. Speckle-tracking echocardiography has been proven to be feasible to follow-up changes induced by exercise training and detraining and might provide an early possibility to differentiate between physiological and pathological conditions.

Serum Uric Acid Is Independently Associated with Coronary Calcification in an Asymptomatic Population.

Detecting early-stage atherosclerosis is an important step towards cardiovascular disease prevention. Coronary artery calcium (CAC) score is a sensitive and non-invasive tool for detecting coronary atherosclerosis. Higher serum uric acid (SUA) levels are known to be associated with cardiovascular diseases. However, there is inconsistency regarding the independence of the association. The aim of our study was to assess the association of CAC and SUA in an asymptomatic population. CAC scans of 281 participants were analyzed in a voluntary screening program. A health questionnaire, physical examination, and laboratory tests were also performed. Participants with a history of cardiovascular disease were excluded from the analysis. 36.3% (n = 102) of the participants had no detectable CAC and 13.9% (n = 39) had a CAC score of > 300. SUA showed positive correlation with CAC score (0.175, p < 0.01). SUA was independently associated with Ca score > 300 (OR 5.17, p = 0.01) after the effects of conventional risk factors were eliminated.

Acute, total occlusion of the left main stem: coronary intervention options, outcomes, and recommendations.

INTRODUCTION: Acute, total occlusion of the unprotected left main stem (uLMo) in acute coronary syndrome (ACS) patients is a catastrophic event often accompanied by sudden cardiac death (SCD) and/or cardiogenic shock (CS) with high mortality rates and limited methods of successful treatment. Emergent, surgical and percutaneous revascularization has been reported before, yet comprehensive data remains scarce. AIM: To examine emergency percutaneous coronary intervention (PCI) outcomes in ACS cases presenting with uLMo. MATERIAL AND METHODS: Data on 23 subjects undergoing primary PCI in uLMo cases were analyzed. The primary end-point was in-hospital death; secondary end-points were successful salvage of coronary anatomy and 90-day major cardiac adverse events (MACE). RESULTS: About 40% of LM occlusion cases presented following successful on-site cardio-pulmonary resuscitation (CPR). Of all patients arriving for treatment the occluded LM was successfully opened and stented in ~90% of cases. CS was present in > 85% of cases, and circulatory support in the form of intra-aortic balloon pump and/or extracorporeal membrane oxygenation systems was applied in every eligible case (~80%). The in-hospital death rate was 56%, mostly including individuals requiring prior CPR. At 6 months, additional MACE rates were low at 8.7%. CONCLUSIONS: We found that uLMo ACS cases often present with preceding CPR and mostly in manifest CS. Coronary salvage is generally successful, yet uLMo even with optimal present day complex treatment yields quite high mortality rates. This is especially true for patients receiving prior CPR. In surviving patients, however, 6-month MACE rates are acceptable.

Nitric oxide for inhalation in ST-elevation myocardial infarction (NOMI): a multicentre, double-blind, randomized controlled trial.

Aims: Inhalation of nitric oxide (iNO) during myocardial ischaemia and after reperfusion confers cardioprotection in preclinical studies via enhanced cyclic guanosine monophosphate (cGMP) signalling. We tested whether iNO reduces reperfusion injury in patients with ST-elevation myocardial infarction (STEMI; NCT01398384). Methods and results: We randomized in a double-blind, placebo-controlled study 250 STEMI patients to inhale oxygen with (iNO) or without (CON) 80 parts-per-million NO for 4 h following percutaneous revascularization. Primary efficacy endpoint was infarct size as a fraction of left ventricular (LV) size (IS/LVmass), assessed by delayed enhancement contrast magnetic resonance imaging (MRI). Pre-specified subgroup analysis included thrombolysis-in-myocardial-infarction flow in the infarct-related artery, troponin T levels on admission, duration of symptoms, location of culprit lesion, and intra-arterial nitroglycerine (NTG) use. Secondary efficacy endpoints included IS relative to risk area (IS/AAR), myocardial salvage index, LV functional recovery, and clinical events at 4 and 12 months. In the overall population, IS/LVmass at 48-72 h was 18.0 ± 13.4% in iNO (n = 109) and 19.4 ± 15.4% in CON [n = 116, effect size -1.524%, 95% confidence interval (95% CI) -5.28, 2.24; P = 0.427]. Subgroup analysis indicated consistency across clinical confounders of IS but significant treatment interaction with NTG (P = 0.0093) resulting in smaller IS/LVmass after iNO in NTG-naïve patients (n = 140, P < 0.05). The secondary endpoint IS/AAR was 53 ± 26% with iNO vs. 60 ± 26% in CON (effect size -6.8%, 95% CI -14.8, 1.3, P = 0.09) corresponding to a myocardial salvage index of 47 ± 26% vs. 40 ± 26%, respectively, P = 0.09. Cine-MRI showed similar LV volumes at 48-72 h, with a tendency towards smaller increases in end-systolic and end-diastolic volumes at 4 months in iNO (P = 0.048 and P = 0.06, respectively, n = 197). Inhalation of nitric oxide was safe and significantly increased cGMP plasma levels during 4 h reperfusion. The Kaplan-Meier analysis for the composite of death, recurrent ischaemia, stroke, or rehospitalizations showed a tendency toward lower event rates with iNO at 4 months and 1 year (log-rank test P = 0.10 and P = 0.06, respectively). Conclusions: Inhalation of NO at 80 ppm for 4 h in STEMI was safe but did not reduce infarct size relative to absolute LVmass at 48-72h. The observed functional recovery and clinical event rates at follow-up and possible interaction with nitroglycerine warrant further studies of iNO in STEMI.

Routine aortic valve replacement followed by a myriad of complications: role of 3D printing in a difficult cardiac surgical case.

Aortic valve replacement (AVR) is a routine cardiac surgical intervention that is rarely associated with severe complications. In this report, we present a complex and unique case following AVR in a middle-aged woman. We show the growing necessity for a strong cooperation between interventional cardiologists and cardiac surgeons, together with the emerging role of cardiac tomography based three-dimensional printing technique in planning and executing precision surgery within the chest.

Signs of subclinical atherosclerosis in asymptomatic patients at increased risk of type 2 diabetes mellitus.

AIMS: We aimed to study carotid intima media thickness (CIMT) in asymptomatic patients with an increased risk of type 2 diabetes mellitus (T2DM) and in a pre-diabetic state. METHODS: Diabetes risk assessment was performed in 2420 participants in a voluntary screening program between 2011 and 2013. The risk of T2DM was estimated by the Findrisc scoring system (FR). A FR≥12 was considered as increased risk. HbA1c% between 5.7 and 6.4% signified a pre-diabetic state. Carotid duplex scan was performed and CIMT above 0.9 mm was regarded as pathological. Patients with T2DM or a history of cardiovascular disease were excluded. RESULTS: Overall 1475 subjects were included. Four groups were compared: "control" (normal HbA1c, FR<12), "HbA1c only" (HbA1c: 5.7-6.4%, FR<12), "Findrisc only" (normal HbA1c, FR≥12) and "combined" (HbA1c: 5.7-6.4%, FR≥12). Frequency of pathological maximal CIMT was 9.4%, 19.7%, 27.4% and 36.4% in the groups, respectively (p<0.001). Logistic regression analysis revealed that compared to control subjects, sex and risk factor-adjusted Odds Ratios for the presence of pathological maximal CIMT were 2.2 (p<0.001), 3.4 (p<0.001) and 5.1 (p<0.001) for the groups, respectively. CONCLUSIONS: Evaluation of Findrisc score and HbA1c at population level may facilitate early recognition of subclinical vascular complications even in the pre-diabetic state.

Association between VEGF Gene Polymorphisms and In-Stent Restenosis after Coronary Intervention Treated with Bare Metal Stent.

Background. In-stent restenosis (ISR) is the gradual narrowing of the vessel lumen after coronary stent implantation due to the increase in vascular smooth muscle cell proliferation. Vascular endothelial growth factor (VEGF) protein plays an important role in this process. Our aim was to analyze the association of single nucleotide polymorphisms of the VEGF gene (rs2010963 and rs6999447) with the occurrence of ISR after coronary artery bare metal stent (BMS) implantation. Methods. 205 patients with a history of BMS implantation and a repeated coronarography were prospectively enrolled. Patients were assigned to diffuse restenosis group (n = 105) and control group (n = 100) and VEGF genotypes were determined. Results. Diffuse ISR was significantly more frequently observed in patients with homozygous normal genotype of rs2010963 polymorphism, and this polymorphism was independently associated with diffuse ISR. Conclusions. RS2010963 is associated with higher incidence of development of diffuse coronary ISR in patients treated with BMS implantation.