Good safety practice in a randomized controlled trial (CadColdEx) involving increased cardiac workload in patients with coronary artery disease

Abstract Background Methodological information acknowledging safety of cardiac patients in controlled medical experiments are lacking. The descriptive report presents one good practice for considering safety in a randomized controlled study involving augmented cardiovascular strain among persons with coronary artery disease (CAD). Methods The patients were pre-selected by a cardiologist according to strictly defined selection criteria. Further confirmation of eligibility included screening of health. In addition, assessments of physical capacity by a graded bicycle ergometer test were implemented and safety monitored by an exercise physiologist and medical doctor. In this context, an emergency simulation was also carried out. A total of 18 CAD patients each underwent four different experimental interventions where either temperature (+ 22 °C and − 15 °C) and the level of exercise (rest and brisk walking) were employed for 30 min in random order (72 experiments). Baseline (20 min) and follow-up (60 min) measurements were conducted resting at + 22 °C. ECG, and brachial blood pressure were measured and perceived exertion and symptoms of chest pain inquired throughout the experiments. An emergency nurse was responsible for the health monitoring and at least two persons followed the patient throughout the experiment. A medical doctor was available on call for consultation. The termination criteria followed the generally accepted international guidelines for exercise testing and were planned prior to the experiments. Results The exercise test simulation revealed risks requiring changes in the study design and emergency response. The cardiovascular responses of the controlled trials were related to irregular HR, ST-depression or post-exercise hypotension. These were expected and the majority could be dealt on site by the research personnel and on call consultation. Only one patient was encouraged to seek for external health care consultation. Conclusions Appropriate prospective design is a key to safe implementation of controlled studies involving cardiac patients and stimulation of cardiovascular function. This includes careful selection of participants, sufficient and knowledgeable staff, as well as identifying possible emergency situations and the required responses. Trial registration ClinicalTrials ID: NCT02855905

The effects of submaximal exercise and cold exposure on blood coagulation parameters in coronary artery disease patients

Abstract Background: Both exercise and cold exposure increase blood coagulation potential but their combined effects are not known. The purpose of the present study was to assess blood coagulation factors in response to submaximal exercise in the cold environment among patients with stable coronary artery disease (CAD). Methods: Sixteen men (61.1 ± 7.1 years) with stable CAD participated in three 30-min experimental conditions (seated rest in − 15 °C and exercise in both + 22 °C and − 15 °C) in random order. The employed exercise consisted of brisk walking (66–69% of maximal heart rate). Factor VII (FVII), fibrinogen, D-dimer and von Willebrand factor (vWF) were analyzed from blood samples obtained before, immediately and one hour after each experiment. Results: On average, FVII activity (95% confidence interval, CI) was 123 (108–143) %, 123 (106–140) %, 121 (103–139) % (baseline, recovery 1, recovery 2), fibrinogen concentration (95% CI) 3.81 (3.49–4.12) g/l, 3.71 (3.34–4.08) g/l, 3.65 (3.26–4.05) g/l, D-dimer concentration (95% CI) 0.42 (0.28–0.56) µg/ml, 0.42 (0.29-.55) µg/ml and 0.39 (0.29–0.49) µg/ml, and vWF activity (95% CI) 184 (135–232) %, 170 (128–212) % and 173 (129–217) % after exercise in the cold. Average FVII activity varied from 122 to 123%, fibrinogen concentration from 3.71 to 3.75 g/l, D-dimer concentration from 0.35 to 0.51 µg/ml and von Willebrand factor activity from 168 to 175% immediately after each three experimental condition. Conclusions: Our findings suggest that submaximal lower body exercise carried out in a cold environment does not significantly affect blood coagulation parameters among patients with stable CAD

Cardiovascular responses to dynamic and static upper-body exercise in a cold environment in coronary artery disease patients

Purpose Upper-body exercise performed in a cold environment may increase cardiovascular strain, which could be detrimental to patients with coronary artery disease (CAD). This study compared cardiovascular responses of CAD patients during graded upper-body dynamic and static exercise in cold and neutral environments. Methods 20 patients with stable CAD performed 30 min of progressive dynamic (light, moderate, and heavy rating of perceived exertion) and static (10, 15, 20, 25 and 30% of maximal voluntary contraction) upper body exercise in cold (− 15 °C) and neutral (+ 22 °C) environments. Heart rate (HR), blood pressure (BP) and electrocardiographic (ECG) responses were recorded and rate pressure product (RPP) calculated. Results Dynamic-graded upper-body exercise in the cold increased HR by 2.3–4.8% (p = 0.002–0.040), MAP by 3.9–5.9% (p = 0.038–0.454) and RPP by 18.1–24.4% (p = 0.002–0.020) when compared to the neutral environment. Static graded upper-body exercise in the cold resulted in higher MAP (6.3–9.1%; p = 0.000–0.014), lower HR (4.1–7.2%; p = 0.009–0.033), but unaltered RPP compared to a neutral environment. Heavy dynamic exercise resulted in ST depression that was not related to temperature. Otherwise, ECG was largely unaltered during exercise in either thermal condition. Conclusions Dynamic- and static-graded upper-body exercise in the cold involves higher cardiovascular strain compared with a neutral environment among patients with stable CAD. However, no marked changes in electric cardiac function were observed. The results support the use of upper-body exercise in the cold in patients with stable CAD.peerReviewe

Good safety practice in a randomized controlled trial (CadColdEx) involving increased cardiac workload in patients with coronary artery disease

Abstract Background: Methodological information acknowledging safety of cardiac patients in controlled medical experiments are lacking. The descriptive report presents one good practice for considering safety in a randomized controlled study involving augmented cardiovascular strain among persons with coronary artery disease (CAD). Methods: The patients were pre-selected by a cardiologist according to strictly defined selection criteria. Further confirmation of eligibility included screening of health. In addition, assessments of physical capacity by a graded bicycle ergometer test were implemented and safety monitored by an exercise physiologist and medical doctor. In this context, an emergency simulation was also carried out. A total of 18 CAD patients each underwent four different experimental interventions where either temperature (+ 22 °C and − 15 °C) and the level of exercise (rest and brisk walking) were employed for 30 min in random order (72 experiments). Baseline (20 min) and follow-up (60 min) measurements were conducted resting at + 22 °C. ECG, and brachial blood pressure were measured and perceived exertion and symptoms of chest pain inquired throughout the experiments. An emergency nurse was responsible for the health monitoring and at least two persons followed the patient throughout the experiment. A medical doctor was available on call for consultation. The termination criteria followed the generally accepted international guidelines for exercise testing and were planned prior to the experiments. Results: The exercise test simulation revealed risks requiring changes in the study design and emergency response. The cardiovascular responses of the controlled trials were related to irregular HR, ST-depression or post-exercise hypotension. These were expected and the majority could be dealt on site by the research personnel and on call consultation. Only one patient was encouraged to seek for external health care consultation. Conclusions: Appropriate prospective design is a key to safe implementation of controlled studies involving cardiac patients and stimulation of cardiovascular function. This includes careful selection of participants, sufficient and knowledgeable staff, as well as identifying possible emergency situations and the required responses. Trial registration: ClinicalTrials ID: NCT02855905

Central aortic hemodynamics following acute lower and upper-body exercise in a cold environment among patients with coronary artery disease

Abstract Exercise is beneficial to cardiovascular health, evidenced by reduced post-exercise central aortic blood pressure (BP) and wave reflection. We assessed if post-exercise central hemodynamics are modified due to an altered thermal state related to exercise in the cold in patients with coronary artery disease (CAD). CAD patients (n = 11) performed moderate-intensity lower-body exercise (walking at 65–70% of HRmax) and rested in neutral (+ 22 °C) and cold (− 15 °C) conditions. In another protocol, CAD patients (n = 15) performed static (five 1.5 min work cycles, 10—30% of maximal voluntary contraction) and dynamic (three 5 min workloads, 56–80% of HRmax) upper-body exercise at the same temperatures. Both datasets consisted of four 30-min exposures administered in random order. Central aortic BP and augmentation index (AI) were noninvasively assessed via pulse wave analyses prior to and 25 min after these interventions. Lower-body dynamic exercise decreased post-exercise central systolic BP (6–10 mmHg, p < 0.001) and AI (1–6%, p < 0.001) both after cold and neutral and conditions. Dynamic upper-body exercise lowered central systolic BP (2–4 mmHg, p < 0.001) after exposure to both temperatures. In contrast, static upper-body exercise increased central systolic BP after exposure to cold (7 ± 6 mmHg, p < 0.001). Acute dynamic lower and upper-body exercise mainly lowers post-exercise central BP in CAD patients irrespective of the environmental temperature. In contrast, central systolic BP was elevated after static exercise in cold. CAD patients likely benefit from year-round dynamic exercise, but hemodynamic responses following static exercise in a cold environment should be examined further

Cardiovascular responses to cold and submaximal exercise in patients with coronary artery disease

Regular year-round exercise is recommended for patients with coronary artery disease (CAD). However, the combined effects of cold and moderate sustained exercise, both known to increase cardiac workload, on cardiovascular responses are not known. We tested the hypothesis that cardiac workload is increased, and evidence of ischemia would be observed during exercise in the cold in patients with CAD. Sixteen men (59.3 +/- 7.0 yr, means +/- SD) with stable CAD each underwent 4, 30 min exposures in a randomized order: seated rest and moderate-intensity exercise [walking, 60%-70% of max heart rate (HR)] performed at +22 degrees C and -15 degrees C. Systolic brachial blood pressure (SBP), HR, electrocardiogram (ECG), and skin temperatures were recorded throughout the intervention. Rate pressure product (RPP) and ECG parameters were obtained. The combined effects of cold and submaximal exercise were additive for SBP and RPP and synergistic for HR when compared with rest in a neutral environment. RPP (mmHg.beats/min) was 17% higher during exercise in the cold (18,080 +/- 3540) compared with neutral (15,490 +/- 2,940) conditions (P = 0.001). Only a few ST depressions were detected during exercise but without an effect of ambient temperature. The corrected QT interval increased while exercising in the cold compared with neutral temperature (P = 0.023). Recovery of postexercise blood pressure was similar regardless of temperature. Whole body exposure to cold during submaximal exercise results in higher cardiac workload compared with a neutral environment. Despite the higher RPP, no signs of myocardial ischemia or abnormal ECG responses were observed. The results of this study are useful for planning year-round exercise-based rehabilitation programs for stable CAD patients.</p

Endothelial function in response to exercise in the cold in patients with coronary artery disease

Abstract Background: Regular long‐term physical exercise has favourable effects on endothelial function in patients with coronary artery disease (CAD). However, the effects of an acute exercise bout in the cold on endothelial function are not known. Methods: At first, the effects of moderate‐intensity aerobic lower‐body exercise were assessed in CAD patients (n = 16) in a neutral [+22°C] and cold [−15°C] environment. Secondly, responses to static and dynamic upper‐body exercise in a neutral [+22°C] and cold [−15°C] environment were investigated in CAD patients (n = 15). All experiments were performed in a random order. Endothelial function was measured by flow‐mediated dilation (FMD) of the brachial artery in response to reactive hyperaemia, before and after the exposures in a neutral environment. Results: No significant temperature*exercise*condition (pre–post) interaction was observed in FMD% when comparing rest versus aerobic exercise or static versus dynamic upper‐body exercise. Relative reactive hyperaemia during FMD protocol, measured by changes in shear rate, was elevated after rest compared to aerobic exercise (p = 0.001) and after static compared to dynamic upper‐body exercise (p &lt; 0.001). However, no significant temperature*exercise*condition interaction was observed when FMD% was normalized for shear rate. Conclusions: Endothelial function to an acute bout of exercise among CAD patients was not modified by the environmental temperature where the exercise was performed. The present findings argue against the hypothesis that exercise in cold environmental conditions impairs endothelial function in patients with CAD

Cardiovascular responses to dynamic and static upper-body exercise in a cold environment in coronary artery disease patients

Abstract Purpose: Upper-body exercise performed in a cold environment may increase cardiovascular strain, which could be detrimental to patients with coronary artery disease (CAD). This study compared cardiovascular responses of CAD patients during graded upper-body dynamic and static exercise in cold and neutral environments. Methods: 20 patients with stable CAD performed 30 min of progressive dynamic (light, moderate, and heavy rating of perceived exertion) and static (10, 15, 20, 25 and 30% of maximal voluntary contraction) upper body exercise in cold (− 15 °C) and neutral (+ 22 °C) environments. Heart rate (HR), blood pressure (BP) and electrocardiographic (ECG) responses were recorded and rate pressure product (RPP) calculated. Results: Dynamic-graded upper-body exercise in the cold increased HR by 2.3–4.8% (p = 0.002–0.040), MAP by 3.9–5.9% (p = 0.038–0.454) and RPP by 18.1–24.4% (p = 0.002–0.020) when compared to the neutral environment. Static graded upper-body exercise in the cold resulted in higher MAP (6.3–9.1%; p = 0.000–0.014), lower HR (4.1–7.2%; p = 0.009–0.033), but unaltered RPP compared to a neutral environment. Heavy dynamic exercise resulted in ST depression that was not related to temperature. Otherwise, ECG was largely unaltered during exercise in either thermal condition. Conclusions: Dynamic- and static-graded upper-body exercise in the cold involves higher cardiovascular strain compared with a neutral environment among patients with stable CAD. However, no marked changes in electric cardiac function were observed. The results support the use of upper-body exercise in the cold in patients with stable CAD. Trial registration: Clinical trial registration NCT02855905 August 2016