In-Hospital and One-Year Outcomes of Patients after Early and Late Resuscitated Cardiac Arrest Complicating Acute Myocardial Infarction-Data from a Nationwide Database.

The prognostic role of early (less than 48 h) resuscitated cardiac arrest (ErCA) complicating acute myocardial infarction (AMI) is still controversial. The present study aimed to analyse the short-term and one-year outcomes of patients after ErCA and late resuscitated cardiac arrest (LrCA) compared to patients without cardiac arrest (CA) complicating AMI. Data from the prospective nationwide Polish Registry of Acute Coronary Syndromes (PL-ACS) were used to assess patients with resuscitated cardiac arrest (rCA) after AMI. Baseline clinical characteristics and the predictors of all-cause death were assessed. The all-cause mortality rate, complications, performed procedures, and re-hospitalisations were assessed for the in-hospital period, 30 days after discharge, and 6- and 12-month follow-ups. Among 167,621 cases of AMI, CA occurred in 3564 (2.1%) patients, that is, 3100 (87%) and 464 (13%) patients with ErCA and LrCA, respectively. The mortality rates in the ErCA vs. LrCA and CA vs. non-CA groups were as follows: in-hospital: 32.1% vs. 59.1% (p < 0.0001) and 35.6% vs. 6.0% (p < 0.0001); 30-day: 2.2% vs. 3.2% (p = 0.42) and 9.9% vs. 5.2% (p < 0.0001); 6-month: 9.2% vs. 17.9% (p = 0.0001) and 12.3% vs. 21.1% (p < 0.0001); and 12-month: 12.3% vs. 21.1% (p = 0.001) and 13% vs. 7.7% (p < 0.0001), respectively. ErCA (hazard ratio (HR): 1.54, confidence interval (CI):1.28-1.89; p < 0.0001) and LrCA (HR: 2.34, CI: 1.39-3.93; p = 0.001) increased the risk of 12-month mortality. During the 12-month follow-up, patients after LrCA more frequently required hospitalisation due to heart failure compared to patients after ErCA. ErCA was related to a higher hospitalisation rate due to coronary-related causes and a higher rate of percutaneous coronary intervention. An episode of LrCA was associated with higher in-hospital and long-term mortality compared to ErCA. ErCA and LrCA were independent risk factors for one-year mortality.

Impact of diabetes mellitus on outcomes in patients with myocardial infarction according to varying degrees of left ventricular systolic dysfunction.

BACKGROUND: Diabetes mellitus (DM) is known to contribute to unfavorable short- and long-term outcomes in patients with myocardial infarction (MI). Particularly poor outcomes are associated with left ventricular systolic dysfunction after an MI. Our study aimed to compare the short- and long-term outcomes of MI in patients with DM and varying degrees of left ventricular systolic dysfunction with the corresponding outcomes in a non-diabetic control group. METHODS: This analysis focused on patients with MI registered in the Polish National Registry of Acute Coronary Syndrome between 2009 and 2011. For this analysis, diabetic patients were additionally stratified into three subgroups depending on the degree of left ventricular systolic dysfunction, as assessed during their hospitalization for MI. Subsequently, the 30-day, 12-month, and 36-month outcomes in the diabetic study subgroups were compared with those in the corresponding non- -diabetic subgroups. RESULTS: This analysis encompassed a nationwide cohort of 58 123 patients. Twelve- and 36-months mortality was greater in diabetic patients than in non-diabetic patients. The highest 36-months mortality (46.64%) was in the group of patients with DM and reduced ejection fraction (EF) <40%. Multivariate analysis showed diabetes and low EF to be independent risk factors for 36-month mortality, increasing the risk of death by 35% for diabetes and by 30% for each 5-percentage point EF decrease. Higher mortality was observed in older patients, smokers, and patients with ischemic heart disease before the index hospitalization. CONCLUSIONS: Both diabetes and reduced EF proved to be independent risk factors for increased mortality over a long-term follow-up after MI.

Isoprenaline induced Takotsubo syndrome: Histopathological analyses of female rat hearts.

BACKGROUND: Takotsubo syndrome (TTS) is a stress-induced disorder affecting mostly postmenopausal women. The aim of the study was to evaluate isoprenaline (ISO) dependent female rat model and histopathological characteristics in TTS. METHODS: Forty-nine Sprague Dawley female rats, 12 weeks old, were injected intraperitoneally with a single dose of ISO at doses 50 (n = 8), 75 (n = 6), 100 (n = 3), 150 (n = 27) and 200 (n = 5) mg/kg body weight (bw). The control group (n = 6) was injected with physiological saline. The echocardiographic examination to assess wall motion abnormalities took place 24, 48, 72 h, and 7 days post-ISO. Histopathological analysis was performed on the basis of hematoxylin-eosin staining. RESULTS: The total mortality rate was 3/49 (6.12%). The optimum dose of ISO to induce TTS was 150 mg/kg bw and 21/27 (77.77%) rats showed apical ballooning. Histopathological analysis revealed focal necrosis/apoptosis of cardiomyocytes with inflammatory and fibroblast-like cell infiltration. Foci were the most numerous in the central muscle layer with apical-basal gradient 24, 48, 72 h post-ISO (p < 0.05). Significant differences were noted 48 h post-ISO in the central layer in apical vs basal segments (p = 0.0032), in the endocardial layer in apical vs basal segments (0.00024) and in mid-cavital vs. basal segments (p = 0.0483). The number of foci in endocardium of apical region differ 48 h post-ISO in rats with a dose of 150 vs. 200 mg/kg bw (p = 0.0084). CONCLUSIONS: The ISO female rat model of TTS is associated with higher optimum dose and lower mortality in comparison with the male TTS model. TTS presents as a singles cardiomyocyte disorder, foci concerned mainly central muscle layer with apical-basal gradient.

Three-year mortality after acute myocardial infarction in patients with different diabetic status.

Introduction: The prevalence of diabetes mellitus (DM) in patients with myocardial infarction (MI) is estimated at about 25%. Short- and long-term prognosis is worse in patients with DM and hyperglycemia compared with nondiabetics. Objectives: Our aim was to analyze the impact of DM and transient hyperglycemia on in-hospital complications and long-term outcomes in patients with MI. Patients and methods: We evaluated a prospective cohort of 58 394 patients with MI in the Polish Registry of Acute Coronary Syndromes (PL-ACS) in terms of in-hospital complications and 30-day, 12-month, and 36-month outcomes between 2009 and 2012. Results: Patients with type 1 DM (T1DM) and type 2 DM (T2DM) underwent invasive diagnostic and therapeutic procedures less frequently than those without diabetes, transient hyperglycemia, and new-onset DM (P <⁠0.001). T2DM was associated with a significantly higher risk of MI complicated by cardiogenic shock. The rates of pulmonary edema in the transient hyperglycemia group and the DM group were 2-fold higher than in the nondiabetic group (P <⁠0.001). T1DM and T2DM were associated with a significantly higher risk of death. Unadjusted 3-year all-cause death rates in patients with T1DM, T2DM, transient hyperglycemia, new-onset diabetes and those without diabetes were 26.8%, 25.6%, 18.5%, 17.9%, and 16.2%, respectively. Hazard ratios (95% CI) adjusted for age, sex, clinical characteristics, and revascularization were 1.49 (1.12­2.00), 1.20 (1.14­1.27), 0.94 (0.67­1.31), and 0.66 (0.34­1.28), respectively. Conclusions: T1DM and T2DM are associated with elevated in-hospital and long-term mortality rates after MI. Diabetics and patients with transient hyperglycemia are more likely to develop significant in-hospital complications compared with nondiabetics. No significant differences regarding acute mechanical complications were noted between populations.

Results of targeted temperature management of patients after sudden out­of­hospital cardiac arrest: a comparison between intensive general and cardiac care units.

BACKGROUND: Targeted temperature management (TTM) is used to treat patients after sudden out­of­hospital cardiac arrest (OHCA). AIMS: The aim of the study was to compare the results of TTM between intensive general and cardiac care units (ICCUs). METHODS: The Polish Registry of Therapeutic Hypothermia obtained data on 377 patients with OHCA from 26 centers (257 and 120 patients treated at the ICCU and intensive care unit [ICU], respectively). Eligibility for TTM was based on the current inclusion criteria for therapy. Medical history as well as data on TTM and additional treatment were analyzed. The main outcomes included in­hospital survival and complications as well as neurologic assessment using the Glasgow Coma Scale (GCS) and Rankin scale. RESULTS: Both ICU and ICCU patients were mostly male (mean age, 60 years). There were no significant differences regarding the medical history, mechanism of arrhythmia responsible for OHCA, GCS score on admission, time of cardiopulmonary resuscitation activities, and the time to target temperature (33°C). Coronary angiography and the use of dual antiplatelet therapy, intra­aortic balloon pump, intravascular hypothermia, dopamine, and dobutamine were more common in ICCU patients, while ICU patients more often received norepinephrine. Pneumonia and acute renal failure were more frequent in the ICCU group. Death occurred in 17% and 20% of ICU and ICCU patients, respectively (P = 0.57). The Rankin class after 48 hours since discontinuation of sedation and at discharge was comparable between groups. CONCLUSIONS: The ICCU has become a considerable alternative to the ICU to treat OHCA patients with TTM.

Comparative effectiveness of torasemide versus furosemide in symptomatic therapy in heart failure patients: Preliminary results from the randomized TORNADO trial.

BACKGROUND: Recent reports suggest that torasemide might be more beneficial than furosemide in patients with symptomatic heart failure (HF). The aim was to compare the effects of torasemide and furosemide on clinical outcomes in HF patients. METHODS: This study pilot consisted of data from the ongoing multicenter, randomized, unblinded endpoint phase IV TORNADO (NCT01942109) study. HF patients in New York Heart Association (NYHA) II-IV class with a stable dose of furosemide were randomized to treatment with equipotential dose of torasemide (4:1) or continuation of unchanged dose of furosemide. On enrollment and control visit (3 months after enrollment) clinical examination, 6-minute walk test (6MWT) and assessment of fluid retention by ZOE Fluid Status Monitor were performed. The primary endpoint was a composite of improvement of NYHA class, improvement of at least 50 m during 6MWT and decrease in fluid retention of at least 0.5 W after 3-months follow-up. RESULTS: The study group included 40 patients (median age 66 years; 77.5% male). During follow-up 7 patients were hospitalized for HF worsening (3 in torasemide and 4 in furosemide-treated patients). The primary endpoint reached 15 (94%) and 14 (58%) patients on torasemide and furosemide, respectively (p = 0.03). CONCLUSIONS: In HF patients treated with torasemide fluid overload and symptoms improved more than in the furosemide group. This positive effect occurred already within 3-month observation.

Toll-like receptor expression and apoptosis morphological patterns in female rat hearts with takotsubo syndrome induced by isoprenaline.

AIMS: Toll-like receptors (TLR) and apoptosis were indicated as important factors in heart failure. Our aim was to characterize the morphological pattern of apoptosis, TLR2, TLR4, and TLR6 expression in female rat hearts in the model of takotsubo syndrome (TTS). MAIN METHODS: 60 Sprague-Dawley female rats were treated with a single dose of 150 mg/kg b.wt. of isoprenaline (ISO) or 0.9% NaCl (controls). Hearts were collected 24, 48, 72 h and 7 days post-ISO injection. 32/60 hearts were used in immunohistopathological studies and 28/60 in real time. KEY FINDINGS: Apoptosis was observed 24 h post-ISO in cardiomyocytes, 24, 48, 72 h and 7 days post-ISO in infiltrating inflammatory cells, 7 days post-ISO in endothelial cells of vessels. Diffuse TLR4CD68 (CD68, a macrophage marker) and TLR6CD68 positive cells and TLR2, TLR4, TLR6 mononuclear cells were observed in both acute and recovery phase of TTS. In the foci located in the neighborhood of damaged (necrotic/apoptotic) cardiomyocytes in TTS, high (strong) protein expression of TLR2 (TLR2high) was observed: 24, 48, 72 h post-ISO; TLR4high - 48 and 72 h post-ISO; TLR6high - 48 h post-ISO. Whereas in cardiomyocytes of remote myocardium: TLR2high - 72 h post-ISO; TLR4high - 24 and 72 h post-ISO; TLR6high - 24 h post-ISO. TLR2 mRNA was down-regulated 48 and 72 h post-ISO whereas TLR4 up-regulated 7 days post-ISO. SIGNIFICANCE: The expression pattern of apoptosis and TLR differs in the course of TTS in comparison with the control rats. We hypothesize that innate immunity and apoptosis may play a crucial role in TTS pathophysiology.

Dual antiplatelet therapy is safe and efficient after left atrial appendage closure.

BACKGROUND: Despite results of the PROTECT AF trial, many patients undergoing left atrial appendage closure (LAAC) have unconditional contraindications to warfarin. AIM: We sought to investigate whether double antiplatelet therapy (DAPT) is safe in patients after LAAC. METHODS: Forty-four consecutive patients (22 males, mean age 74 ± 7.8 years) with non-valvular atrial fibrillation (NVAF) underwent LAAC procedure using a Watchman device followed by DAPT (75 mg/d aspirin and 75 mg/d clopidogrel). After the procedure and during 98 days' follow-up including transoesophageal echocardiography, peri-procedural complications and clinical outcomes were investigated. RESULTS: Mean CHA2DS2-VASc score was 4.9 ± 1.5 and mean HAS-BLED score was 3.6 ± 0.8. The main LAAC indication was contraindication to anticoagulation reflected by HAS-BLED score ≥ 3 observed in 95.5% cases (among them history of bleeding in 38 patients, 90.5%). 36.4% of patients have history of stroke or transient ischaemic attack. The procedure was successful in 97.7%. Peri-procedural complications were tamponade (2.3%) and one death (2.3%) unrelated to the procedure with no bleeding or vascular complications. During follow-up neither stroke nor bleeding were observed, whereas two device related thrombi and two unrelated deaths occurred. CONCLUSIONS: LAAC followed by DAPT seems to be a safe and efficient alternative for stroke prevention in patients with NVAF who have contraindications to anticoagulation therapy. This strategy may provide a significant reduction of events such as stroke and bleeding versus the score-predicted rate.

Assessment of the myocardial FDG-PET image quality with the use of maximal Standardized Uptake Value myocardial to background index. Application of the results in regard to semiquantitative assessment of myocardial viability with cardiac dedicated softwar.

BACKGROUND: The objective of this study was to semiquantitatively assess the degree of myocardial fluorodeoxyglucose (FDG) uptake in glucose-loaded myocardial viability positron emission tomography/computed tomography (PET/CT) scans, to calculate the myocardial to background index, and correlate the index with image quality assessed on the basis of visual qualitative assessment. MATERIAL AND METHODS: The myocardial FDG-PET/CT study was carried out in 69 non-diabetic patients, who had known coronary artery disease, by intravenous injection of 250 ± 70 MBq (range: 180-320 MBq) FDG. Images were interpreted visually and patients were divided into three groups according to the grade of myocardial uptake: optimal, suboptimal, and uninterpretable. Semiquantitative analysis was performed by calculating the standardized uptake value (SUVmax) for myocardium and background (blood pool) activity, and expressed as the myocardial to background (M/B) activity ratio. RESULTS: On the basis of visual (qualitative) analysis, 60/69 (86.96%) patients showed optimal quality of FDG cardiac uptake, 3/69 (4.35%) were suboptimal, and uninterpretable FDG PET scan results were found in 6/69 (8.70%) patients. The M/B index was found to be significantly higher in images of optimal vs. suboptimal quality (6.87 ± 3.99 vs. 1.65 ± 0.78 respectively; p < 0.0001). CONCLUSIONS: The index ratio of 2.2, which is consistent with the upper borderline value for visually uninterpretable images, was considered the cut-off value for scans of optimal and non-optimal quality.

Cardiovascular risk reduction in sedentary postmenopausal women during organised physical activity.

BACKGROUND: Cardiovascular (CV) diseases are a major cause of death in elderly women. Aerobic training improves component CV risk factors. Long-term, higher-intensity, group-based and home-based exercise training has been shown to improve exer-cise performance. However, it is not clear if short-term, group-based or home-based training with an educational programme permanently improves cardiometabolic parameters in elderly women. AIM: The aim of the study was to evaluate the effectiveness of organised physical activity programmes dedicated to elderly, sedentary women. METHODS: Thirty-five sedentary women, aged > 55 years (mean 65.4 ± 7.3 years) were enrolled in a two-week group-based physical training programme of moderate intensity (2.5-5.0 METs) followed by three months of organised, home-based physical activity targeting all major muscle groups with special emphasis on postural muscles, combined with an educational programme about physical activity and CV risk. Eighteen months of self-guided physical activity was the final stage of training. Medical examination and blood samples were collected at baseline and after each step of exercises. RESULTS: Each step of training resulted in a reduction of systolic and diastolic blood pressure (p < 0.05), body mass index (p < 0.05), waist to hip ratio (p < 0.02), and low-density lipoprotein (p < 0.05) as compared to baseline. The time of exercise (p < 0.01), maximal tolerated load, and maximal oxygen consumption (p < 0.001) were significantly improved after two-weeks of training, as well as the high-density lipoprotein (p < 0.001). These changes remained significant after three months. Finally, the 10-year risk of fatal CV disease reduced significantly (p < 0.05). After 18 months 2/3 of subjects continued physical activity at a sufficient level to achieve additional health benefits according to the World Health Organisation. CONCLUSIONS: Organised, group-based exercise followed by home-based training and self-guided physical activities constantly improves cardiometabolic parameters and reduces CV risk.

The impact of torasemide on haemodynamic and neurohormonal stress, and cardiac remodelling in heart failure - TORNADO: a study protocol for a randomized controlled trial.

BACKGROUND: Approximately 50% of heart failure patients are readmitted to hospital within 6 months, owing to deterioration of their condition. Thus, symptomatic treatment of heart failure requires significant improvement. The aim of this study is to compare the effects of torasemide and furosemide on biochemical parameters of haemodynamic and neurohormonal compensation, myocardial remodelling, clinical outcomes and quality of life in patients with chronic heart failure. METHODS: This is a multicentre, randomized, open, blinded endpoint phase-IV trial. The study includes 120 heart failure patients in NYHA (New York Heart Association) functional class II-IV, treated with optimal heart failure therapy, with indications for use of loop diuretics. At enrolment, patients are stable, with a fixed dose of loop diuretics. Patients are randomized to treatment with furosemide or torasemide (randomization 1:1). After randomization, the current fixed dose of furosemide is continued or is replaced by an equipotential dose of torasemide (4:1). The study consists of two control visits (3 and 6 months after enrolment) with minimal follow-up of 6 months. Assessment involves clinical examination, Quality of Life Questionnaire, laboratory tests, echocardiography, electrocardiography, 24 h Holter-electrocardiography monitoring, 6 -min walk test and assessment of fluid retention. Any need for dose adjustment is assessed during the observation. The primary objective is to compare the effects of torasemide and furosemide on clinical and biochemical parameters of haemodynamic and neurohormonal compensation and myocardial remodelling. Secondary objectives include monitoring of: changes in signs and symptoms of heart failure, NYHA functional class, quality of life, dosage changes, rate of readmissions and mortality. DISCUSSION: Despite decades of the diuretic's history, knowledge about diuretic therapy is still unsatisfactory. The most widely used diuretic, furosemide, has a stormy pharmacokinetics and pharmacodynamics, and is associated with a high risk of mortality and hospitalization for worsening heart failure. Reports are very encouraging and suggest beneficial effects of torasemide. Hence, there is a need for further studies of the overall effect of torasemide, compared with furosemide. This can translate into improved quality of life and better prognosis of patients with heart failure. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01942109 . Registered on 24 August 2013.