GLP-1 is an independent predictor of long-term mortality in patients with myocardial infarction complicated by cardiogenic shock – a substudy of the IABP-SHOCK II trial

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
G Fuernau ◽  
M Lehrke ◽  
C Jung ◽  
F Kahles ◽  
C Lebherz ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiogenic Shock ◽  
Independent Predictor ◽  
Funding Source ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Landmark Analysis ◽  
Markers Of Inflammation

Abstract Background The incretin hormone Glucagon-like-peptide 1 (GLP-1) is a major stimulus for glucose dependent insulin secretion and holds cardioprotective efficacy. This has made the GLP-1 system a preferred target for diabetes therapy. Secretion of GLP-1 happens in response to nutritional but also inflammatory stimuli. Consequently, marked elevation of circulating GLP-1 levels were found in critically ill patients featuring marked association to markers of inflammation. Purpose Our study sought to investigate GLP-1 levels in patients with cardiogenic shock (CS) complicating myocardial infarction and a possible prognostic correlation to short- and long-term outcome. Methods We serially assessed circulating GLP-1 levels in a prospectively planned biomarker substudy in the IABP-SHOCK II trial. Blood samples were drawn during index PCI and at day 2. The blood was centrifuged immediately, and serum was frozen at −87°C. GLP-1 was measured with a standard ELISA-kit. All-cause mortality at short- (30 days), intermediate- (1 year) and long-term (6 years) follow-up was used for outcome assessment. Results In this study we found circulating GLP-1 to be markedly elevated in patients with myocardial infarction complicated by CS (n=172) at time of index PCI. Patients with fatal short-term outcome (n=70) exhibited higher GLP-1 levels (86 [45–130] pM) at ICU admission in comparison to patients with 30-day survival (48 [33–78] pM; p<0.001) (n=102). In repeated measures ANOVA the course of GLP-1 levels between baseline and day 2 showed a significant interaction between survivors and non-survivors (p=0.04). By univariate Cox-regression analysis GLP-1 levels >median were predictive of short- (hazard ratio [HR] 2.43; 95% confidence interval [CI] 1.50–3.94; p<0.001), intermediate- (HR 2.46; 95% CI 1.62–3.76; p<0.001) and long-term (HR 2.12; 95% CI 1.44–3.11; p<0.001) outcome. This association remained after multivariable correction (HR 2.01; 95% CI 1.37–3.07; p<0.001). In a landmark analysis we found a significant higher mortality in patients with GLP-1 levels >median from day 30 to 1 year (HR 2.56; 95% CI 1.08–6.09; p=0.03). In contrast, beyond 1 year up to 6 years no difference has been observed anymore (HR 1.02; 95% CI 0.41–2.58; p=0.96). Conclusions Elevated plasma levels of GLP-1 are an independent predictor for impaired prognosis in patients with myocardial infarction complicated by CS at short-, intermediate and long-term follow-up. In a landmark analysis this prognostic effect is sustained up to 1 year. The functional relevance of GLP-1 in this context is currently unknown and needs further investigations. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): German Research Foundation (DFG), German Heart Research Foundation

Novel biomarker of Cysteine-rich angiogenic inducer 61 (Cyr61) predicts long-term outcome of ST-elevation myocardial infarction

2019 ◽  
Author(s):  
Rui Xiang ◽  
Min Mao ◽  
Ping Tang ◽  
Jun Gu ◽  
Kanghua Ma
Keyword(s):  
Myocardial Infarction ◽  
St Elevation Myocardial Infarction ◽  
Cardiac Complications ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Risk Of Death ◽  
Secondary Endpoints ◽  
St Elevation

Abstract Background: Cysteine-rich angiogenic inducer 61 (Cyr61) is a matricellular protein participating in the angiogenesis, inflammation, and fibrotic tissue repair. Previous study has proven its value in diagnosing and risk stratification of ST-elevation myocardial infarction (STEMI). However, there is no study focusing on Cyr61 and the long-term outcome of STEMI. Methods: A total of 426 patients diagnosed with STEMI were enrolled in this study. Blood sample was acquired 24 hours after the admission. The patients were required long-term follow-up after the discharge, when primary endpoint of all-cause death and secondary endpoint of cardiac complications were observed. Cox hazard ratio model and survival analysis were used to compare the risk of patients with higher level and lower level of Cyr61. Results: We conducted an average of (48.4 ± 17.8) months of follow-up, during which a total of 28 deaths happened (6.6%), while 106 episodes of secondary endpoints occurred (24.9%). Patients with higher quartile (Q4) Cyr61 were at higher risk of death [HR 3.404 95%CI (1.574-7.360), P<0.001] when compared with lower three quartiles (Q1-Q3) Cyr61. In terms of secondary endpoints, patients with Q4 Cyr61 were subject to 4.718 [95%CI (3.189-6.978) , P<0.001] times of risk compared with Q1-Q3 Cyr61. Conclusions: For STEMI Patients, those with increased Cyr61 have higher risk of all-cause death and cardiac complications. Therefore, Cyr61 may be a useful tool in predicting the long-term prognosis of STEMI.

Treatment of virus negative chronic myocarditis: long term follow-up of TIMIC trial

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
C Chimenti ◽  
M.A Russo ◽  
A Frustaci
Keyword(s):  
Left Ventricular Ejection ◽  
Funding Source ◽  
Inflammatory Cardiomyopathy ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Dose Treatment ◽  
Term Efficacy ◽  
Long Term Follow Up

Abstract Background The TIMIC trial demonstrated the short term efficacy of immunosuppression (IMS) in virus-negative inflammatory cardiomyopathy. However long term outcome of patients responsive to this treatment is still unclear. Purpose To assess the long term outcome of patients enrolled in the TIMIC trial. Methods The 85 (51 M, 34 F, 42.7±14.7 years) patients with endomyocardial biopsy proven virus-negative chronic inflammatory cardiomyopathy, enrolled in the TIMIC trial and treated either with prednisone and azathioprine (prednisone 1mg kg–1 day–1 for 4 weeks followed by 0.33 mg kg–1 day–1 for 5 months and azathioprine 2 mg kg–1 day–1 for 6 months) or placebo for 6 months, were evaluated in a long-term follow-up of up to 18 years (mean 15.2±2.0 SD, range 12–18 ys). Patients treated with placebo at the end of the 6-month enrollment because of the lack of improvement received IMS for further 6 months. Results At 6 months' follow-up 89% patients showed a significant improvement of left ventricular ejection fraction compared to baseline (LVEF rising from 27.0±5.7 to 46.2±6.4, % p&lt;0.001). This improvement was maintained in the long term follow-up (LVEF 51.1±6.4%, p&lt;0.001). Importantly, the 42 patients initially on placebo showed an improvement comparable to the branch on IMS either on short (EF from 27.7% to 46.8±6.2%) and on long term follow up (LVEF from 27.7% to 50.6±5.6%, p&lt;0.001). Nine patients (11%) did not show a significant improvement of LVEF either at short and long term follow-up and among them 4 died and 2 had a cardiac transplantation. Five patients (5.8%) had a relapse of the cardiac inflammatory process that promptly responded to a new TIMIC dose treatment. Four of them (4F, 41.2±9.4 ys age) had concomitant autoimmune diseases and the relapse was within the first 2 years after IMS discontinuation. One patient (M, 56 ys) had a relapse after 10 years following a flu-like syndrome. Conclusion Immunosuppressive therapy of virus negative inflammatory cardiomyopathy warrants in susceptible patients a long term recovery of heart function with very low incidence of recurrences, that respond to a new TIMIC protocol dose treatment. Long term efficacy of TIMIC-IMS therapy Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): AIFA

P3458Sex, myocardial infarction, critical state and long-term outcome

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
V Kanic ◽  
D Suran ◽  
I Krajnc ◽  
I Balevski ◽  
F H Naji ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiogenic Shock ◽  
Renal Dysfunction ◽  
Critical State ◽  
Term Outcome ◽  
Term Survival ◽  
Long Term Outcome ◽  
Female Sex ◽  
Long Term Mortality

Abstract Background Myocardial infarction (MI) remains the most common cause of heart failure (HF). Data on sex-related critical state in patients with MI who underwent PCI and their long-term outcome, are missing. Purpose We evaluated whether there is a sex difference in critical state and if sex is associated with long-term survival in these patients. Methods We defined critical state as cardiogenic shock and/or mechanical ventilation and/or intra-aortic balloon pump and/or ejection fraction≤30%. We analyzed data on 5669 patients with MI treated with percutaneous interventions (PCI). The criteria for critical state were fulfilled by 539 (9.5%) patients, of whom 172 (31.9%) were women. Long-term mortality was observed. The median follow-up time was 5.0 (25th, 75th percentile: 3,8) years. Data were analyzed using descriptive statistics. Results The incidence of critical state was similar in both sexes [172 (9.8%) women compared to 367 (9.4%) men]. The women were older, suffered more diabetes and renal dysfunction, presented more often in cardiogenic shock, and had a higher maximal troponin/body surface area level. After adjustment, female sex was associated with critical state (adjusted OR 1.38; 95% CI 1.07 to 1.77; p=0.013). However, similar unadjusted long-term mortality was observed [111 (64.5%) of women died compared to 244 (66.5%) men, p=0.70]. Furthermore, after adjustment for potential confounders, female sex was associated with a 24% lower risk of dying in the long term (adjusted HR 0.76; 95% CI 0.58 to 0.98; p=0.037) compared to men (Figure 1). Other predictors of long-term mortality in patients with critical state were age, hyperlipidemia, renal dysfunction, and dual antiplatelet therapy. Figure 1 Conclusion Female sex was associated with critical state. However, the unadjusted long-term mortality was similar in both sexes. In addition, female sex was associated with better long-term survival in patients with critical state. Further investigation is required to answer these associations.

scholarly journals Frequency and Impact of Molecular Response’s with Nilotinib (Tasigna) in Patients (Pts) with Newly Diagnosed Philadelphia Chromosome (Ph)-Positive Chronic Myelogenous Leukemia in Early Chronic Phase (CML-CP)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3156-3156
Author(s):  
Naval Daver ◽  
Hagop M. Kantarjian ◽  
Susan O'Brien ◽  
Elias Jabbour ◽  
Sherry Pierce ◽  
...  
Keyword(s):  
Research Funding ◽  
Cytogenetic Response ◽  
Molecular Response ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Landmark Analysis ◽  
Intent To Treat ◽  
Dose Reductions

Abstract Background: Nilotinib is a BCR-ABL tyrosine kinase inhibitor with approximately 50-fold higher inhibitory activity than imatinib in preclinical studies. Aim: We initiated a phase II study (in 2005) to evaluate the efficacy of frontline nilotinib in pts with newly diagnosed CML-CP. The primary objective of this report was to estimate major molecular response (MMR) and complete molecular response (CMR: minimum 100,000 ABL copies) rates with prolonged follow-up, and the impact of MMR and CMR on long-term outcome. Methods: Pts with Ph-positive or BCR-positive CML in early CML-CP [i.e., time from diagnosis 12 months] with <1 month of prior interferon-alpha and/or imatinib were eligible. Nilotinib was initiated at a dose of 400 mg twice daily. Results for CCyR and MMR are reported as intent-to-treat unless specifically annotated as response among evaluable pts (eval). Results: 140 pts have been treated as of August 1, 2014. Herein we focus on the initial 109 pts who have a minimum follow-up of 12 months. The median (med) follow-up for these 109 pts is 52.2 months (range, 0.9 to 108.0+). The med age was 50 years (range, 17 to 86). 73% of pts had Sokal low risk. 17 (16%) had received imatinib for <1 months (med 18 days; range, 5 to 29 days). Overall, 92% (100/109) pts achieved a complete cytogenetic response [CCyR] with a med time to CCyR of 2.9 months (range, 2.1 to 8.1+). The rates of CCyR at 3, 6, 12 and 18 months were 80% (eval:83%), 86% (eval:95%), 83% (eval:99%), and 77% (eval:100%), respectively. Overall, MMR and CMR were achieved in 90% (98/109) and 45% (49/109) of the pts. Med time to MMR and CMR was 3.3 months (range, 2.4 to 48.0+) and 23.1 months (range, 3.2 to 86.0+), respectively. BCR-ABL/ABL at 3 months was <10% in 94% (eval:100%) and <1% in 89% (eval: 94%). BCR-ABL/ABL at 6 months was <1% in 81% (eval:89%) and <0.1% in 65% (eval:72%) in pts evaluated at these time points. MMR was observed in 65% (eval:72%) at 6 months, 71% (eval:87%) at 12 months, and 70% (eval:90%) at 18 months. CMR was observed in 9% (eval:11%) at 6 months, 14% (eval:17%) at 12 months, and 15% (eval:19%) at 18 months. We further analyzed the association between CCyR and molecular response (Table 1). For example, among the 84 pts who were in CCyR at 18 months: MMR was achieved in 90% of these pts including MR3 in 31%, MR4 in 13%, MR4.5 in 27%, and CMR in 19%. Estimated 3-year and 5-year overall survival (OS) is 98% and 91%, respectively. Estimated 3-year and 5-year failure-free survival (FFS) is 82% and 73%, respectively. On an intent-to-treat analysis the FFS among pts who achieved CMR was superior to those who did not achieve CMR (P<0.001, respectively). On a landmark analysis, which included only those pts who received nilotinib for a minimum of 24 months (med time to CMR among pts who achieved CMR=23.1 months) the FFS among pts who achieved CMR was superior to those who did not achieve CMR (P=0.008) (Figure 1). Dose-reductions were performed in 41 (38%) pts: 30 pts required 1 dose-reduction and 11 pts required 2 or more dose-reductions. The most frequent reasons for dose-reductions included increased liver enzymes (n=8), rash (n=5), pain/arthralgia (n=4), cardiac and QTc (n=4), fatigue (n=5), and neutropenia (n=2). The actual med dose remains 800 mg daily. 29 (27%) pts are off study due to toxicity in 8 (cardiac=3, liver enzymes=4, fatigue=1), inadequate response in 5 (3 never achieved adequate and 2 lost adequate response), progression to blast-phase in 3, death in 5 (all 5 non-CML related causes), 8 due to pt choice (financial=1, non-compliance=3, pt choice=1) Conclusion: Nilotinib 400 mg twice daily is very effective. The cumulative rates of CCyR, MMR and CMR were 92%, 90%, and 45%, respectively. CMR rates continue to improve with long-term follow-up. Attainment of CMR is associated with improved long-term outcome. Table 1: Molecular response rates among pts who achieve CCyR CCyR MR3 but not MR4 MR4 but not MR4.5 MR4.5 but not CMR CMR No MMR 3 months 87/105 (83%) 39/87 (45%) 5/87 (6%) 8/87 (9%) 2/87 (2%) 33/87 (38%) 6 months 94/99 (88%) 35/94 (38%) 6/94 (6%) 20/94 (21%) 10/94 (11%) 23/94 (24%) 12 months 90/91 (99%) 38/90 (42%) 3/90 (3%) 23/90 (26%) 15/90 (17%) 11/90 (12%) 18 months 84/84 (100%) 26/84 (31%) 11/84 (13%) 23/84 (27%) 16/84 (19%) 8/84 (10%) PCyr, partial cytogenetic response; Min, mimimal; Inev, inevaluable; IM, insufficient metaphase Figure 1: FFS CMR versus no CMR by landmark analysis for pts who received at least 24.0 months of nilotinib Figure 1:. FFS CMR versus no CMR by landmark analysis for pts who received at least 24.0 months of nilotinib Disclosures Daver: Novartis: Research Funding. Jabbour:Novartis: Advisory board membership Other, Research Funding. Cortes:Novartis: Advisory Board membership Other, Research Funding.

Long-term outcome and risk assessment in premature acute myocardial infarction: A 10-year follow-up study

2017 ◽  
Vol 240 ◽  
pp. 37-42 ◽  
Author(s):  
Max-Paul Winter ◽  
Hermann Blessberger ◽  
Arman Alimohammadi ◽  
Noemi Pavo ◽  
Kurt Huber ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Risk Assessment ◽  
Acute Myocardial Infarction ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Follow Up Study

scholarly journals Effect of Contrast-Induced Nephropathy on the Long-Term Outcome of Patients with Non-ST Segment Elevation Myocardial Infarction

2015 ◽  
Vol 5 (2) ◽  
pp. 116-124 ◽  
Author(s):  
Burak Turan ◽  
Ayhan Erkol ◽  
Mehmet Gül ◽  
Uğur Fındıkçıoğlu ◽  
İsmail Erden
Keyword(s):  
Myocardial Infarction ◽  
Contrast Induced Nephropathy ◽  
Term Outcome ◽  
Long Term Outcome ◽  
St Segment Elevation ◽  
Segment Elevation Myocardial Infarction ◽  
St Segment ◽  
Long Term Follow Up

Background: Contrast-induced nephropathy (CIN) has been traditionally associated with increased mortality and adverse cardiovascular events. We sought to determine whether CIN has a negative impact on the long-term outcome of patients with non-ST segment elevation myocardial infarction (NSTEMI). Methods: A total of 312 consecutive patients (mean age 59 years, 76% male) who presented with NSTEMI and had undergone an early invasive procedure were retrospectively included. CIN was defined as either a 25% or 0.5-mg/dl increase in baseline serum creatinine (Cr) 72 h after the procedure. The primary endpoint of the study was mortality in the long-term follow-up (38 months, interquartile range 30-40). The secondary endpoint consisted of mortality and myocardial infarction (MI). Results: CIN developed in 30 (9.6%) patients. Independent predictors of CIN were the contrast volume-to-Cr clearance ratio, left ventricular ejection fraction and hemoglobin concentration. The primary (20 vs. 8.5%, p = 0.042) and secondary endpoints (33.3 vs. 17%, p = 0.029) were observed more frequently in patients with CIN during long-term follow-up. The unadjusted odds ratio (OR) of CIN was 2.55 [95% confidence intervals (CI) 1.04-6.24, p = 0.040] for mortality and 2.15 (CI 1.09-4.25, p = 0.028) for mortality/MI. However, after adjustment for confounding factors, CIN was not an independent predictor of either mortality (OR 1.62, CI 0.21-12.57, p = 0.646) or mortality/MI (OR 1.12, CI 0.31-4.0, p = 0.860). Conclusion: The effect of CIN on the long-term outcome of patients with NSTEMI was substantially influenced by confounding factors. CIN was a marker, rather than a mediator, of increased cardiovascular risk, and the baseline renal function was more conclusive as a long-term prognosticator.

Long-term outcome of adult patients with total anomalous pulmonary venous connection: data from the SACHER registry and a French center

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Touray ◽  
J Bouchardy ◽  
M Schwerzmann ◽  
M Greutmann ◽  
D Tobler ◽  
...  
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
Ventricular Arrhythmias ◽  
Congenital Heart ◽  
Funding Source ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Anomalous Pulmonary Venous Connection

Abstract Introduction Total anomalous pulmonary venous connection is a rare cyanotic congenital heart disease, where all pulmonary veins aberrantly connect to a systemic vein or the right atrium. The only curative treatment is surgery allowing the patients to reach adulthood. This study describes the long-term outcome of these individuals focusing on arrhythmias. Methods Clinical, surgical, imaging and invasive data were retrospectively reviewed from 7 centers participating in the Swiss Adult Congenital Heart disease Registry (SACHER) and one French center. Results A total of 57 patients were identified and analyzed 22±8 years after surgery. At last follow-up, 21% of patients presented cardiac symptoms, mainly palpitations. No patient had pulmonary hypertension or a relevant valvulopathy. Echocardiography revealed in 5 (8.8%) patients a dilated right ventricle (RV) and in 3 (5.3%) patients a diminished RV systolic function. Exercise capacity was normal in most patients (table). Cardiac magnetic resonance imaging found in 2 (4%) had a residual shunt with an mean Qp:Qs of 1.25, due to a single anomalously connected pulmonary vein. Holter recordings revealed arrhythmias in 23% of patient. Ten (17.5%) had atrial fibrillation, flutter or tachycardia. Three (5%) patients presented ventricular arrhythmias: two patients showed non-sustained ventricular tachycardia and one patient complex ventricular extrasystoles. Four patients (7%) were on antiarrhythmic medication for supraventricular arrhythmias. Three patients (5%) underwent an electrophysiological study with a mean time since surgery of 20 years. Three (5%) patients underwent pacemaker implantation within 3 weeks to 36 months after surgical correction, which were removed in 2 patients after 7 years. Age and the presence of a valvulopathy at follow-up predicted tachyarrhythmia on binomial logistic regression analysis (p&lt;0.03). Conclusions In adult survivors after TAPVC repair, supraventricular but also ventricular arrhythmias are frequently observed which appears to be related to age and valvular lesions at follow-up. This study underlies the importance of long-term follow-up as some of the patients currently without arrhythmia will probably develop rhythm disorders in the future. Funding Acknowledgement Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): Unrestricted grant by Actelion SA, Switzerland

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