The impact of exercise capacity in the atherosclerotic patient: Keep on walking!

__Abstract__ Peripheral arterial disease (PAD) is a manifestation of systemic arteriosclerosis. It is a common disease affecting millions of people. Depending on the age of the investigated population prevalences between 4% to 29% has been reported. It is alarming that the prevalence is expected to rise in the following decades due to the aging of the western population and the increase of risk factors such as diabetes mellitus, obesity and lack of exercise. Patients with PAD are of an increased risk of cardiovascular events and mortality. In addition, they may also experience signifi cant limitations in their physical functioning and impairment in their quality of life. It is important to diagnose patients with PAD early in the course of the disease to provide them optimal treatment as soon as possible in attempting to lower the complication rates, improve morbidity, mortality and subsequent their quality of life. However, symptoms of PAD are diverse. The classical symptoms are intermittent claudication consisted of calf pain provoked by walking and declining at rest. Earlier investigations, on the other hand, have demonstrated a large range of symptoms ranging from no pain at all till pain at rest . A major problem is that between 20% till 50% of the patients are asymptomatic . Commonly, to identify patients with PAD the resting ankle brachial index (ABI) is used. This is the ratio between the ankle’s systolic blood pressure, measured at the dorsalis pedis or posterial tibial arterie using a Doppler ultrasonic instrument, and the systolic blood pressure at the arm. An ABI below 0.90 is associated with angiographic stenosis of more than 50% . According to the guidelines a resting ABI of < 0.90 is defi ned as PAD. Several studies have found that an ABI of < 0.90 is associated with an increased risk of cardiovascular diseases and mortality. Moreover it can also be used for prognostic risk stratifi cation

Microcirculatory Monitoring in Children with Congenital Heart Disease Before and After Cardiac Surgery

In this prospective observational study, we investigated whether congenital heart disease (CHD) affects the microcirculation and whether the microcirculation is altered following cardiac surgery with cardiopulmonary bypass (CPB). Thirty-eight children with CHD undergoing cardiac surgery with CPB and 35 children undergoing elective, non-cardiac surgery were included. Repeated non-invasive sublingual microcirculatory measurements were performed with handheld vital microscopy. Before surgery, children with CHD showed similar perfused vessel densities and red blood cell velocities (RBCv) but less perfused vessels (p &lt; 0.001), lower perfusion quality (p &lt; 0.001), and higher small vessel densities (p = 0.039) than children without CHD. After cardiac surgery, perfused vessel densities and perfusion quality of small vessels declined (p = 0.025 and p = 0.032), while RBCv increased (p = 0.032). We demonstrated that CHD was associated with decreased microcirculatory perfusion and increased capillary recruitment. The microcirculation was further impaired after cardiac surgery. Decreased microcirculatory perfusion could be a warning sign for altered tissue oxygenation and requires further exploration. Graphical abstract: [Figure not available: see fulltext.].</p

Microcirculatory Monitoring in Children with Congenital Heart Disease Before and After Cardiac Surgery

In this prospective observational study, we investigated whether congenital heart disease (CHD) affects the microcirculation and whether the microcirculation is altered following cardiac surgery with cardiopulmonary bypass (CPB). Thirty-eight children with CHD undergoing cardiac surgery with CPB and 35 children undergoing elective, non-cardiac surgery were included. Repeated non-invasive sublingual microcirculatory measurements were performed with handheld vital microscopy. Before surgery, children with CHD showed similar perfused vessel densities and red blood cell velocities (RBCv) but less perfused vessels (p < 0.001), lower perfusion quality (p < 0.001), and higher small vessel densities (p = 0.039) than children without CHD. After cardiac surgery, perfused vessel densities and perfusion quality of small vessels declined (p = 0.025 and p = 0.032), while RBCv increased (p = 0.032). We demonstrated that CHD was associated with decreased microcirculatory perfusion and increased capillary recruitment. The microcirculation was further impaired after cardiac surgery. Decreased microcirculatory perfusion could be a warning sign for altered tissue oxygenation and requires further exploration

Peri-operative red blood cell transfusion in neonates and infants: NEonate and Children audiT of Anaesthesia pRactice IN Europe: A prospective European multicentre observational study

BACKGROUND: Little is known about current clinical practice concerning peri-operative red blood cell transfusion in neonates and small infants. Guidelines suggest transfusions based on haemoglobin thresholds ranging from 8.5 to 12 g dl-1, distinguishing between children from birth to day 7 (week 1), from day 8 to day 14 (week 2) or from day 15 (≥week 3) onwards. OBJECTIVE: To observe peri-operative red blood cell transfusion practice according to guidelines in relation to patient outcome. DESIGN: A multicentre observational study. SETTING: The NEonate-Children sTudy of Anaesthesia pRactice IN Europe (NECTARINE) trial recruited patients up to 60 weeks' postmenstrual age undergoing anaesthesia for surgical or diagnostic procedures from 165 centres in 31 European countries between March 2016 and January 2017. PATIENTS: The data included 5609 patients undergoing 6542 procedures. Inclusion criteria was a peri-operative red blood cell transfusion. MAIN OUTCOME MEASURES: The primary endpoint was the haemoglobin level triggering a transfusion for neonates in week 1, week 2 and week 3. Secondary endpoints were transfusion volumes, 'delta haemoglobin' (preprocedure - transfusion-triggering) and 30-day and 90-day morbidity and mortality. RESULTS: Peri-operative red blood cell transfusions were recorded during 447 procedures (6.9%). The median haemoglobin levels triggering a transfusion were 9.6 [IQR 8.7 to 10.9] g dl-1 for neonates in week 1, 9.6 [7.7 to 10.4] g dl-1 in week 2 and 8.0 [7.3 to 9.0] g dl-1 in week 3. The median transfusion volume was 17.1 [11.1 to 26.4] ml kg-1 with a median delta haemoglobin of 1.8 [0.0 to 3.6] g dl-1. Thirty-day morbidity was 47.8% with an overall mortality of 11.3%. CONCLUSIONS: Results indicate lower transfusion-triggering haemoglobin thresholds in clinical practice than suggested by current guidelines. The high morbidity and mortality of this NECTARINE sub-cohort calls for investigative action and evidence-based guidelines addressing peri-operative red blood cell transfusions strategies. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT02350348

The association between peripheral arterial disease, treadmill exercise test parameters and long-term outcome

Peripheral arterial disease (PAD), a manifestation of systemic artheriosclerosis, is affecting millions of people with prevalences between 4 to 29%, and is expected to rise in the following decades [1, 2]. According to the guidelines, a resting ankle brachial index (ABI) &lt; 0.90 is defined as PAD, which is related to a higher cardiovascular morbidity and mortality [3, 4]. Surprisingly, in contrast to patients with coronary arterial disease, the value of the exercise test in patients with PAD is still unclear and hardly investigated. Nevertheless, the exercise test may provide a large amount of important clinical data to identify patients with increased cardiovascular risks. Recent publications have also shown that resting ABI between 0.90-1.10, thus classified as 'normal' according to the guidelines, was associated with a higher mortality [5-7]. In today's clinical practice, the ABI measured at rest is still the most used method to diagnose PAD. However, more than 30% of the patients with resting ABI ≥ 0.90 demonstrated after a treadmill exercise test an ABI &lt; 0.90 and were associated with a higher mortality rate [8]. These patients would have been missed according to the current definitions. Not only exercise ABI, but also other factors which may have an important role in the prognosis of PAD can be identified with exercise tests. For example, a hypertensive blood pressure response and a hypotensive blood pressure response at a treadmill exercise test, are associated with an almost two-fold increased risk of cardiovascular death [9, 10]. Also, walking distance impairment was strongly associated with mortality, cardiac death and quality of life [11, 12]. Combining treadmill variables, exercise ABI, walking distance and blood pressure response, with the current known risk factors, provides important additional prognostic information of cardiovascular morbidity and mortality. Furthermore, not only a decline in ABI, but also a decline in walking distance turned out to be a strong prognostic factor of long-term mortality as well [13]. This indicates that exercise tests could be used not only for risk stratification but also for identifying progressive disease.Exercise tests might also be used for early risk factor modification. For instance, early treatment of cardiovascular risk factors such as life style changes, exercise training and optimal medical treatment with statins and beta-blockers, for example, have shown to be effective in patients with PAD [2, 4, 14, 15]. However, it is unknown if, when and how patients, especially with mild and borderline impaired ABI values must be treated.In conclusion, treadmill exercise test parameters are important to identify patients with increased mortality risks, which would otherwise remain unrecognised and untreated, and to identify patients with progressive PAD. However, further research is needed to investigate which and when treatment is needed to lower cardiovascular risks in these patients.</p

The association between peripheral arterial disease, treadmill exercise test parameters and long-term outcome

Peripheral arterial disease (PAD), a manifestation of systemic artheriosclerosis, is affecting millions of people with prevalences between 4 to 29%, and is expected to rise in the following decades [1, 2]. According to the guidelines, a resting ankle brachial index (ABI) &lt; 0.90 is defined as PAD, which is related to a higher cardiovascular morbidity and mortality [3, 4]. Surprisingly, in contrast to patients with coronary arterial disease, the value of the exercise test in patients with PAD is still unclear and hardly investigated. Nevertheless, the exercise test may provide a large amount of important clinical data to identify patients with increased cardiovascular risks. Recent publications have also shown that resting ABI between 0.90-1.10, thus classified as 'normal' according to the guidelines, was associated with a higher mortality [5-7]. In today's clinical practice, the ABI measured at rest is still the most used method to diagnose PAD. However, more than 30% of the patients with resting ABI ≥ 0.90 demonstrated after a treadmill exercise test an ABI &lt; 0.90 and were associated with a higher mortality rate [8]. These patients would have been missed according to the current definitions. Not only exercise ABI, but also other factors which may have an important role in the prognosis of PAD can be identified with exercise tests. For example, a hypertensive blood pressure response and a hypotensive blood pressure response at a treadmill exercise test, are associated with an almost two-fold increased risk of cardiovascular death [9, 10]. Also, walking distance impairment was strongly associated with mortality, cardiac death and quality of life [11, 12]. Combining treadmill variables, exercise ABI, walking distance and blood pressure response, with the current known risk factors, provides important additional prognostic information of cardiovascular morbidity and mortality. Furthermore, not only a decline in ABI, but also a decline in walking distance turned out to be a strong prognostic factor of long-term mortality as well [13]. This indicates that exercise tests could be used not only for risk stratification but also for identifying progressive disease.Exercise tests might also be used for early risk factor modification. For instance, early treatment of cardiovascular risk factors such as life style changes, exercise training and optimal medical treatment with statins and beta-blockers, for example, have shown to be effective in patients with PAD [2, 4, 14, 15]. However, it is unknown if, when and how patients, especially with mild and borderline impaired ABI values must be treated.In conclusion, treadmill exercise test parameters are important to identify patients with increased mortality risks, which would otherwise remain unrecognised and untreated, and to identify patients with progressive PAD. However, further research is needed to investigate which and when treatment is needed to lower cardiovascular risks in these patients.</p