Improving long-term outcomes of acute cardiovascular syndromes

Although acute cardiovascular care is mainly focused on the management of patients presenting with acute cardiovascular symptoms it must not be forgotten that these syndromes are most often only a short-lived manifestation of an underlying, longer lasting and frequently continuously progressing cardiovascular physiopathology. It is therefore pivotal that acute cardiovascular care aims not only at alleviating the acute symptoms but also at improving the long-term outcome of our patients. A comprehensive risk stratification should be performed in all patients before hospital discharge in order to detect reversible cardiovascular risk factors that can be targeted in order to improve the long-term outcome. Most articles in this issue address different risk factors to be considered in the long-term risk stratification of patients presenting with acute cardiovascular syndromes. Anaemia is observed in about one third of all patients with chronic heart failure and is associated with increased rates of rehospitalisation and mortality. The causes are diverse including decreased haematopoiesis frequently related to the presence of an impaired renal function, iron deficiency and also haemodilution related to the congestive state. In a retrospective analysis of patients presenting with acute heart failure anaemia was observed both on admission and discharge in 55 to 62% of the patients (1). Discharge anaemia was associated with a marked increased risk for short (30 days) and long-term (6 months and one year) rehospitalisation. This study confirms also in acute heart failure the negative prognostic impact of anaemia which apparently is more frequent than in chronic heart failure. Elevated filling pressures and fluid overload in acute heart failure are associated with elevated plasma levels of natriuretic peptides that when measured on admission have been demonstrated to be powerful predictors of adverse cardiovascular events including mortality after hospital discharge. The utility of serial measurement of natriuretic peptides for the risk stratification and patient management after hospital discharge remain a matter of debate. Antigen carbohydrate 125 (CA125) has emerged as a potential biomarker of fluid overload in acute heart failure. In a large observational study of patients with acute heart failure both N-terminal pro B-type natriuretic peptide (NT-proBNP) and CA125 were serially measured during long term follow up after hospital discharge (2). Both biomarkers were associated with increased mortality when elevated on admission, and serial measurements during follow up provided incremental prognostic value over the initial baseline measurements. The combination of the long-term longitudinal changes of both parameters improved further risk stratification after hospital discharge for acute heart failure. Renal insufficiency is an important predictor of both short and long-term adverse events in patients with acute heart failure. Cardiac and renal dysfunction exacerbate each other through multiple mechanisms, including neurohormonal activation, stimulation of inflammation, hemodynamic abnormalities, impaired erythropoiesis, promotion of thrombosis and their respective treatments. Data from the Japanese ATTEND registry on acute heart failure demonstrate that this group of patients are a very heterogeneous population (3). The relationship between renal insufficiency and all-cause mortality of acute heart failure patients varies in this population markedly with the presence of comorbidities or clinical features on admission (ischemic heart disease, diabetes, hyponatraemia, anaemia, atrial fibrillation) and the mode of presentation (new onset versus readmission). In order to improve the risk stratification of patients with acute heart failure a better understanding of the relationships between renal insufficiency and other comorbidities and presentation modes is required. The presence of right ventricular dysfunction or failure in acute heart failure due left-sided heart disease leads to increased morbidity and mortality. In a series of cardiogenic shock patients treated by intra-aortic balloon pump (IABP) patients with biventricular failure needed more often escalation of mechanical cardiac support (MCS) to extracorporeal membrane oxygenation (ECMO) or durable left ventricular assist device (LVAD) implantation (4). In patients with acute heart failure treated by LVAD severe aortic regurgitation results in inadequate mechanical support and refractory cardiogenic shock. Most of these patients are too ill to undergo urgent valve surgery. Urgent transcatheter aortic valve implantation is a feasible and lifesaving treatment option in these patients as is illustrated by a case report and a review of the literature (5). The 12 lead electrocardiogram (ECG) remains the first line immediate bedside investigation in the triage of patients presenting with acute anginal chest pain despite its poor sensitivity (50-60%) for the diagnosis of acute myocardial infarction (AMI). Epicardial potentials derived from body surface potentials mapping using a patient-specific torso model is a novel method that may refine the ECG diagnosis of AMI. in a large prospective series of patients with acute anginal chest pain this novel method significantly improved the sensitivity for AMI diagnosis (6). Subarachnoid haemorrhage may result in repolarisation changes mimicking those in ST segment elevation myocardial infarction (STEMI) (7). Especially in unconscious patients the differential diagnosis maybe vital as the potent antithrombotics used in STEMI may be lethal in patients with subarachnoid haemorrhage. Elevated admission plasma glucose levels >140 mg/dl are associated with adverse clinical outcomes within one year in both diabetic and non-diabetic patients admitted with acute coronary syndrome as is demonstrated by a large Israeli registry (8). Previously unknown hyperglycaemia is frequently detected in patients with acute coronary syndromes (ACS). In these patients hyperglycaemia even below the diabetic threshold is associated with an increased risk of future cardiovascular events and mortality. Lifestyle interventions and pharmacotherapy with metformin may prevent the development of type 2 diabetes mellitus T2DM in patients with prediabetes. A reliable method to detect prediabetes and T2DM in ACS patients is therefore very important. In a prospective study in ACS patients repeated measurements of fasting plasma glucose and haemoglobin A1c during hospitalization and 3 months later reliably identified previously unknown T2DM with high sensitivity and positive predictive value, with limited additive diagnostic value of an oral glucose tolerance test (9). Epicardial adipose tissue has generated increasing interest as a novel biomarker for cardiovascular disease. Analogous to visceral abdominal fat, epicardial adipose tissue produces a number of pro-inflammatory cytokines and has been related to the development and progression of high-risk obstructive coronary atherosclerotic plaques. In a series of high-risk patients with ACS undergoing percutaneous coronary intervention (PCI), epicardial adipose tissue correlated well with established markers of cardiovascular mortality and had a significant predictive value for the three-year incidence of major adverse coronary events (10). The perioperative management of patients under therapy with dual antiplatelet therapy (DAPT) who need cardiac or non-cardiac surgery constitute a clinical dilemma as a choice needs to be made between the risks of surgery-related bleeding or ischaemia due to continuation or withdrawal of DAPT, respectively. A meta-analysis performed on the results of 31 papers on about 50.000 patients shows that treatment with clopidogrel is associated with a 2 to 3 times increased risk of major bleeding complications and an increased mortality but apparently does not reduce the risk of cardiac ischaemic events (11). Elective surgery should therefore be delayed during ongoing clopidogrel therapy for the recommended duration of antiplatelet treatment, whereas in patients needing semi-urgent surgery, the decision to prematurely stop clopidogrel (i.e. five days before surgery) should be considered. Although obesity is a risk factor for coronary artery disease (CAD) it is associated with a more favourable prognosis in CAD patients who undergo coronary artery bypass grafting (CABG) surgery. However, during long-term follow-up up to 20 years after CABG this ‘obesity paradox’ seems to disappear due to the progression of cardiometabolic disease such as diabetes leading to an increased cardiovascular mortality (12). These findings support the need for the prevention of obesity and effective weight loss in all CAD patients, as permanent obesity is associated with increased late mortality following CABG. Rheumatologic disorders are characterised by inflammation and an increased risk of CAD. In a sub-analysis of two all-comer stent trials with contemporary PCI treatment – the BASKET-PROVE I and II trials –the clinical presence of rheumatologic disorders was associated with an increased risk of cardiac death and AMI during long-term (2-year) follow-up, and this particularly in patients with a ST elevation AMI (13). It appears therefore that patients with rheumatologic disorders after PCI for ACS are a high-risk group that need more active screening for progression of CAD.