Cohort Profile: the European Unified Registries On Heart care Evaluation and Randomised Trials (EuroHeart) - Acute Coronary Syndrome and Percutaneous Coronary Intervention.

AIMS: The European Unified Registries On Heart care Evaluation And Randomized Trials (EuroHeart) aims to improve the quality of care and clinical outcomes for patients with cardiovascular disease. The collaboration of acute coronary syndrome/percutaneous coronary intervention (ACS/PCI) registries is operational in seven vanguard European Society of Cardiology member countries. METHODS AND RESULTS: Adults admitted to hospitals with ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI) are included, and individual patient-level data collected and aligned according to the internationally agreed EuroHeart data standards for ACS/PCI. The registries provide up to 155 variables spanning patient demographics and clinical characteristics, in-hospital care, in-hospital outcomes, and discharge medications. After performing statistical analyses on patient data, participating countries transfer aggregated data to EuroHeart for international reporting.Between 1st January 2022 and 31st December 2022, 40 021 admissions (STEMI 46.7%, NSTEMI 53.3%) were recorded from 192 hospitals in the seven vanguard countries: Estonia, Hungary, Iceland, Portugal, Romania, Singapore, and Sweden. The mean age for the cohort was 67.9 (standard deviation 12.6) years, and it included 12 628 (31.6%) women. CONCLUSION: The EuroHeart collaboration of ACS/PCI registries prospectively collects and analyses individual data for ACS and PCI at a national level, after which aggregated results are transferred to the EuroHeart Data Science Centre. The collaboration will expand to other countries and provide continuous insights into the provision of clinical care and outcomes for patients with ACS and undergoing PCI. It will serve as a unique international platform for quality improvement, observational research, and registry-based clinical trials.

Improving outpatient care for heart failure through digital innovation: a feasibility study.

BACKGROUND: Heart failure (HF) affects over 26 million people worldwide. Multidisciplinary management strategies that include symptom monitoring and patient self-care support reduce HF hospitalization and mortality rates. Ideally, HF follow-up and self-care support includes lifestyle-change recommendations and remote monitoring of weight and HF symptoms. Providing these via a digital solution may be ideal for improving HF disease outcomes and reducing the burden on providers and healthcare systems. This study's main objective was to assess the feasibility of a digital solution including remote monitoring, lifestyle-change, and self-care support for HF outpatients in Iceland. METHODS: Twenty HF patients (mean age 57.5 years, 80% males) participated in an 8-week study. They were provided with a digital solution (SK-141), including lifestyle-change and disease self-care support, a remote symptom monitoring system, and a secure messaging platform between healthcare providers and patients. This feasibility study aimed to assess patient acceptability of this new intervention, retention rate, and to evaluate trends in clinical outcomes. To assess the acceptability of SK-141, participants completed a questionnaire about their experience after the 8-week study. Participants performed daily assigned activities (missions), including self-reporting symptoms. Clinical outcomes were assessed with the Hospital Anxiety and Depression Scale and the Kansas City Cardiomyopathy Questionnaire at the study's beginning and end with an online survey. RESULTS: Of the 24 patients invited, 20 were elected to participate. The retention rate of participants throughout the 8-week period was high (80%). At the end of the 8 weeks, thirteen participants completed a questionnaire about their experience and acceptability of the SK-141. They rated their experience positively including on questions whether they would recommend the solution to others (6.8 on a scale of 1-7), whether the solution had improved their life and well-being (5.7 on a scale of 1-7), and whether it was user friendly (5.5 on a scale of 1-7). Many of the clinical parameters studied exhibited a promising trend towards improvement over the 8-week period. CONCLUSION: The digital solution, SK-141, was very acceptable to patients and also showed promising clinical results in this small feasibility study. These results encourage us to conduct a longer, more extensive, adequately powered, randomized-controlled study to assess whether this digital solution can improve the quality of life and clinical outcomes among HF patients.

[Cardiac transplantation and donation in Icelandic patients - indications and outcome].

INTRODUCTION: Information on the number, indications and outcome of cardiac transplantations in Icelandic patients is scarce, as is information on the number of hearts donated from Iceland for cardiac transplantation. MATERIAL AND METHODS: A retrospective study on patients receiving heart transplantation from the first procedure in 1988 until March 2019. Clinical information was gathered from Landspitali Transplantation Clinic, patient charts, and information on donated hearts from the Icelandic Donation Registry. Age-standardized incidence of the procedure was calculated, and overall survival (Kaplan-Meier) estimated. Mean follow-up was 10.3 years. RESULTS: Altogether 24 patients (19 males, median age 38 years, range: 4-65 years) underwent cardiac transplantation; that included one re-transplantation, three simultaneous heart- and lung transplants and two heart- and kidney transplants. The transplantations were performed in Gothenburg (n=20), London (n=3) and Copenhagen (n=2). Most common indications were dilated cardiomyopathy (n=10), congenital heart disease (n=4), and viral myocarditis (n=3). Five patients were bridged left ventricular-assist device preoperatively. Overall survival at 1 and 5 years was 91% and 86%, respectively; median survival being 24 years. The incidence of cardiac transplantation was 2.7 heart-TX pmp/year but increased to 4.6 heart-TX pmp/year after 2008 (p=0.01). During the same period 42 hearts were donated from Iceland for transplantation abroad, the first in 2002 and increasing from 0.8 to 3.0 hearts/year during the first and second half of the study-period, respectively. CONCLUSION: Survival of Icelandic cardiac transplant recipients is good and comparable to larger transplant centers overseas. Number of hearts donated from Iceland have increased and currently Iceland donates twice as many hearts at it receives.

Prevention, Detection, and Management of Heart Failure in Patients Treated for Breast Cancer.

PURPOSE OF REVIEW: Long-term survival has increased significantly in breast cancer patients, and cardiovascular side effects are surpassing cancer-related mortality. We summarize risk factors, prevention strategies, detection, and management of cardiotoxicity, with focus on left ventricular dysfunction and heart failure, during breast cancer treatment. RECENT FINDINGS: Baseline treatment of cardiovascular risk factors is recommended. Anthracycline and trastuzumab treatment constitute a substantial risk of developing cardiotoxicity. There is growing evidence that this can be treated with beta blockers and angiotensin antagonists. Early detection of cardiotoxicity with cardiac imaging and circulating cardiovascular biomarkers is currently evaluated in clinical trials. Chest wall irradiation accelerates atherosclerotic processes and induces fibrosis. Immune checkpoint inhibitors require consideration for surveillance due to a small risk of severe myocarditis. Cyclin-dependent kinases4/6 inhibitors, cyclophosphamide, taxanes, tyrosine kinase inhibitors, and endocrine therapy have a lower-risk profile for cardiotoxicity. Preventive and management strategies to counteract cancer treatment-related left ventricular dysfunction or heart failure in breast cancer patients should include a comprehensive cardiovascular risk assessment and individual clinical evaluation. This should include both patient and treatment-related factors. Further clinical trials especially on early detection, cardioprevention, and management are urgently needed.

[Outcome of coronary artery bypass grafting in women in Iceland].

Introduction The aim of this study was to evaluate the outcome of coronary artery bypass grafting (CABG) in women compared to men, with focus on short-term and long-term complications, 30 day mortality and survival. Materials and methods This was a retrospective study on all CABG patients operated in Iceland between 2001 and 2013. Clinical information was gathered from hospital charts and survival data was obtained from the National Statistics in Iceland. Overall survival was estimated with the Kaplan- Meier method. Logistic and Cox regression analysis were used to identify predictors of operative mortality and long-term survival. Mean follow-up was 6.8 years. Results Of 1755 patients 318 were women (18%). Women were on average four years older than men at the time of operation (69 vs. 65 yrs, p<0.001). Female patients had a higher incidence of hypertension (72 vs. 64%, p=0.009) and their EuroSCOREst was higher (6.1 vs. 4.3, p<0.001). The prevalence of diabetes, dyslipidemia and the extent of coronary artery disease was comparable between groups. The rate of short-term complications, both minor (53% vs. 48%, p=0.07) and major (27% vs. 32%, p=0.2), was similar and operative mortality for women was not statistically different from males (4% vs. 2%, p=0.08). Female gender was neither found to be a predictor of 30-day mortality (OR 0.99; 95%-CI: 0.98-1.01) nor survival (HR 1,08; 95%-ÖB: 0,82-1,42). Conclusions The number of women that undergo CABG is low and they are four years older than men when operated on. As is the case with men, outcome following CABG in Iceland is very good for women, their overall five-year survival being 87%.

Profibrinolytic effect of the epigenetic modifier valproic acid in man.

AIMS: The aim of the study was to test if pharmacological intervention by valproic acid (VPA) treatment can modulate the fibrinolytic system in man, by means of increased acute release capacity of tissue plasminogen activator (t-PA) as well as an altered t-PA/Plasminogen activator inhibitor -1 (PAI-1) balance. Recent data from in vitro research demonstrate that the fibrinolytic system is epigenetically regulated mainly by histone deacetylase (HDAC) inhibitors. HDAC inhibitors, including VPA markedly upregulate t-PA gene expression in vitro. METHODS AND RESULTS: The trial had a cross-over design where healthy men (n = 10), were treated with VPA (Ergenyl Retard) 500 mg depot tablets twice daily for 2 weeks. Capacity for stimulated t-PA release was assessed in the perfused-forearm model using intra-brachial Substance P infusion and venous occlusion plethysmography. Each subject was investigated twice, untreated and after VPA treatment, with 5 weeks wash-out in-between. VPA treatment resulted in considerably decreased levels of circulating PAI-1 antigen from 22.2 (4.6) to 10.8 (2.1) ng/ml (p<0.05). It slightly decreased the levels of circulating venous t-PA antigen (p<0.05), and the t-PA:PAI-1 antigen ratio increased (p<0.01). Substance P infusion resulted in an increase in forearm blood flow (FBF) on both occasions (p<0.0001 for both). The acute t-PA release in response to Substance P was not affected by VPA (p = ns). CONCLUSION: Valproic acid treatment lowers plasma PAI-1 antigen levels and changes the fibrinolytic balance measured as t-PA/PAI-1 ratio in a profibrinolytic direction. This may in part explain the reduction in incidence of myocardial infarctions by VPA treatment observed in recent pharmacoepidemiological studies. TRIAL REGISTRATION: The EU Clinical Trials Register 2009-011723-31.

Acute vascular effects of atorvastatin in hypertensive men: a pilot study.

OBJECTIVES: Statins have multiple pleiotropic effects that are independent of their cholesterol-lowering properties including rapid improvement of endothelial function in vitro. Hypertension is characterized by endothelial dysfunction and we hypothesized that a single-dose of atorvastatin may have an acute effect on vascular function. DESIGN: Endothelium-dependent vasodilation (EDV) and endothelium-independent vasodilation were assessed with venous occlusion plethysmography during intra-arterial infusion of acetylcholine (ACH) and sodium nitroprusside (SNP), respectively, in 13 hypertensive men after wash-out from antihypertensive medication. Vasoconstrictive responses were evaluated in response to angiotensin II (Ang II) infusion. The protocol was repeated 1 h after 80 mg oral atorvastatin (ATV; Lipitor(®)). RESULTS: ATV treatment significantly increased baseline forearm blood flow from 3.38 (0.27) to 4.31 (0.35) ml/min/100 ml tissue (p < 0.05). ATV did not affect ACH-induced EDV. Forearm vascular resistance in response to SNP was significantly lowered by ATV (p < 0.05). Vasoconstriction in response to Ang II was significantly inhibited by ATV treatment (p = 0.005). CONCLUSIONS: The observed acute statin effects in hypertension appear to be endothelium-independent and related to vascular smooth muscle cell function. These actions may in part contribute to the beneficial pleiotropic effects of statin therapy even in the acute in vivo setting.

The impaired fibrinolytic capacity in hypertension is unaffected by acute blood pressure lowering.

The endogenous fibrinolytic system and the ability of the endothelium to release tissue-plasminogen activator (t-PA) play a pivotal role to protect humans from atherothrombotic events. We have recently reported that the decreased capacity for t-PA release in hypertension is restored with chronic blood pressure lowering. Thus, we explored if acute blood pressure lowering has the same effect. The capacity for acute t-PA release was investigated in the perfused-forearm model during stimulation by intra-arterial substance P 8 pmol/min in hypertensive subjects. The procedure was then repeated during acute blood pressure lowering (n = 9) induced by sodium nitroprusside (SNP) infusion or during placebo infusion (n = 3). SNP lowered mean arterial pressure from 108.6 (2.6) to 83.0 (2.6) (mean and SEM) mmHg (P < 0.001). Substance P induced significant increase in t-PA release during both high- and low-pressure conditions (P < 0.01, ANOVA). Peak t-PA release rate was 199 (77) and 167 (41) (mean and SEM) ng/min/l tissue, and accumulated t-PA release was 2,395 (750) and 2,394 (473) ng, during high- and low-pressure conditions, respectively. t-PA release and hemodynamic responses were almost identical during high- and low-pressure conditions (P = ns, for all). Acute blood pressure lowering does not restore stimulated t-PA release from the endothelium in hypertensive subjects. These findings are in contrast to previously described effects of chronic blood pressure treatment. Although data need to be confirmed in a larger study, they suggest that high blood pressure decreases the cellular t-PA pool rather than interferes with release mechanisms of the protein.

Transcutaneous electrical nerve stimulation induces vasodilation in healthy controls but not in refractory angina patients.

CONTEXT: Transcutaneous electrical nerve stimulation (TENS) is an effective treatment option to relieve ischemic pain in refractory angina pectoris (RAP). In healthy persons, TENS enhances local blood flow, but the mechanism responsible for the anti-ischemic effect in RAP seems to be different. OBJECTIVE: The aim of the present investigation was to compare the difference in blood flow and vasodilatory response to TENS between angina patients and healthy controls and evaluate how vascular response in these groups is affected by amperage dosage above and below motor threshold levels. METHODS: Our study evaluated upper limb vascular responses to low- and high-dose TENS (below and above motor threshold) in RAP patients compared with healthy controls. TENS was applied on the nondominating forearm. Forearm blood flow (FBF) was measured by venous occlusion plethysmography. Forearm vascular resistance (FVR) was determined (mean arterial pressure [MAP]/FBF). Measurements were done during baseline, low-dose TENS, high-dose TENS, and during recovery. RESULTS: A significant dose-dependent increase in FBF in response to TENS stimulation was seen in controls (n=18) but not in RAP (n=23) (P=0.008). There was no significant difference in FVR ratio (FVR(stim)/FVR(ctrl)) between control (n=7) and RAP (n=23) groups at low dose (controls, 5.7+/-21%; RAP, 9.7+/-20%) or recovery (controls, -4.6+19%; RAP, 5.9+25%). High-dose TENS resulted in a significantly reduced FVR ratio (-16.8+/-11%) in controls (n=7) compared with RAP (1.6+/-32%, n=23) (P=0.02). CONCLUSION: High-dose TENS induces forearm vasodilation in healthy subjects but not in patients with RAP. These findings suggest that TENS has different vascular effects in patients with severe coronary artery disease compared with healthy controls.

ST segment elevation and chest pain during cryoablation of atrial flutter.

A 61-year-old male was treated with cryoablation for typical atrial flutter. Cryoablation was performed percutaneously with an 8-mm tip catheter to achieve a bidirectional conduction block of the cavo-tricuspid isthmus. When freezing at the point where bidirectional isthmus block occurred, the patient experienced chest pain and ECG showed ST segment elevations corresponding to the right coronary artery. Cryoablation may be painless per se, but patients should be told to report chest discomfort and surface ECG must be followed carefully during ablation.

Impaired capacity for stimulated fibrinolysis in primary hypertension is restored by antihypertensive therapy.

The increased risk for myocardial infarction and ischemic stroke in primary hypertension suggests that the condition is associated with prothrombotic mechanisms. We have shown that patients with hypertension have an impaired capacity for acute endothelial tissue-type plasminogen activator (t-PA) release, an important local protective response to prevent formation of intravascular thrombi. The aim of the present study was to investigate whether this impairment could be restored by the lowering of blood pressure. The capacity for acute t-PA release in response to intraarterial infusion of substance P at 8 pmol/min was investigated in a perfused-forearm study in 20 hypertensive patients (12 men and 8 women). Studies were performed when patients were untreated and after 8 weeks of randomized treatment with lisinopril or felodipine that lowered blood pressure by 26/10 and 24/12 mm Hg, respectively. The t-PA release response increased significantly with treatment (ANOVA, P=0.0001), with a similar effect in the 2 treatment groups. The peak release of t-PA increased from 257 (58) to 445 (77) ng/min x L/tissue(-1) (t test, P=0.02). Also, treatment shortened the average time to peak secretion from 6.7 (1.4) to 2.7 (0.3) min (t test, P=0.01). In 6 patients with a delayed secretory peak (9 minutes or later), treatment normalized the response (chi2 test, P=0.008). Antihypertensive therapy restores the capacity for acute t-PA release and improves the rapidity of the response in patients with primary hypertension. Similar responses with the 2 regimens suggest that the improvement is related to the blood pressure reduction as such. This effect may contribute to the thromboprotective effect of antihypertensive treatment.

Prolonged cyclic strain impairs the fibrinolytic system in cultured vascular endothelial cells.

OBJECTIVE: We previously reported that patients with primary hypertension have an impaired ability to release tissue-type plasminogen activator acutely from the vascular endothelium, and recently found that lowering blood pressure can restore this capacity. We hypothesized that the suppression of the fibrinolytic system is caused by the chronic pressure-induced increased haemodynamic load on the endothelium. DESIGN AND METHODS: This study investigated the effect of the tensile force component of blood pressure by exposing cultured human aortic endothelial cells to 10% cyclic strain for 6-72 h. Messenger RNA levels of tissue-type plasminogen activator, urokinase-type plasminogen activator, and plasminogen activator inhibitor 1 were analysed using Taqman real-time reverse transcriptase-polymerase chain reaction and protein release by enzyme-linked immunosorbent assay. RESULTS: Tensile stimulation resulted in a transient initial upregulation of tissue-type plasminogen activator mRNA at 6 h (53%), which declined with time, and at 48 h had switched to a 28% downregulation. The reduction was sustained after 72 h. Tissue-type plasminogen activator protein secretion showed a similar but somewhat delayed response, with a transient increase in release at 6 h (60%), declining to a final 12% reduction at 72 h. A similar pattern was observed for urokinase-type plasminogen activator mRNA. By contrast, plasminogen activator inhibitor 1 mRNA expression and protein secretion increased at all timepoints (16-47%). CONCLUSION: Prolonged tensile stimulation impairs fibrinolytic activity in human aortic endothelial cells by a dual action, with suppression of plasminogen activator expression and increased inhibitor production. This effect of tensile stress may contribute to the reduced fibrinolytic capacity observed in patients with hypertension.

Impaired endothelial release of tissue-type plasminogen activator in patients with chronic kidney disease and hypertension.

We have shown that the capacity for local release of tissue-type plasminogen activator (tPA) from the vascular endothelium is impaired in patients with primary hypertension. Because this response is an important protective mechanism against intravascular clotting, we investigated whether this system is also defective in patients with advanced chronic kidney disease and hypertension. Nine nondiabetic nonsmoking men with chronic kidney disease (glomerular filtration rate 11 to 28 mL/min x 1.73 m2; aged 33 to 75 years) were compared with age-matched healthy controls. Intraarterial infusions of desmopressin, methacholine, and sodium nitroprusside were given locally in the brachial artery. Forearm blood flow was measured by venous occlusion plethysmography and blood collected repeatedly during the desmopressin infusion for determination of stimulated net and total cumulated release of tPA. The maximal release rate of active tPA (P<0.05) and the capacity for acute tPA release were markedly impaired in the renal patients as compared with healthy subjects (ANOVA, P=0.013). Accordingly, the accumulated release of tPA was 1905 (SEM 366) and 3387 (718) ng/L tissue, respectively (P<0.05). However, there were no significant differences in vasodilator responses between the groups. Thus, patients with advanced chronic kidney disease and hypertension have a markedly impaired capacity for acute release of tissue plasminogen activator, despite preserved endothelium-dependent vasodilation. This defect may contribute to a defective local defense against arterial thrombosis.

Fibrinolytic capacity increases with age in healthy humans, while endothelium-dependent vasodilation is unaffected.

The capacity for stimulated endothelial release of tissue-type plasminogen activator (tPA) and endothelium-dependent vasodilation is diminished in patients with cardiovascular risk factors. We examined the effect of age on desmopressin-stimulated tPA release and endothelium-dependent vasodilation, using the perfused-forearm model. Thirty-two healthy subjects were divided into quartiles by age (mean age 24, 36, 54, and 72 years, respectively). Baseline fibrinolytic parameters, baseline forearm blood flow (FBF), and increase in stimulated FBF were all similar across age. By contrast, the capacity for desmopressin- stimulated release of tPA increased linearly by age. For tPA antigen, the total amount released (area-under-the-curve) was 1015, 1282, 2139, and 2845 ng/L tissue (p = 0.011) and the peak release rates were 62, 80, 113, and 163 ng/min/L tissue (p = 0.008) in the age-quartiles, respectively. A similar significant age-related response was observed for tPA activity. We conclude that in healthy individuals there is an up-regulation of the fibrinolytic response by age.