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Concept: Cardiac output


Background Levosimendan is an inotropic agent that has been shown in small studies to prevent or treat the low cardiac output syndrome after cardiac surgery. Methods In a multicenter, randomized, placebo-controlled, phase 3 trial, we evaluated the efficacy and safety of levosimendan in patients with a left ventricular ejection fraction of 35% or less who were undergoing cardiac surgery with the use of cardiopulmonary bypass. Patients were randomly assigned to receive either intravenous levosimendan (at a dose of 0.2 μg per kilogram of body weight per minute for 1 hour, followed by a dose of 0.1 μg per kilogram per minute for 23 hours) or placebo, with the infusion started before surgery. The two primary end points were a four-component composite of death through day 30, renal-replacement therapy through day 30, perioperative myocardial infarction through day 5, or use of a mechanical cardiac assist device through day 5; and a two-component composite of death through day 30 or use of a mechanical cardiac assist device through day 5. Results A total of 882 patients underwent randomization, 849 of whom received levosimendan or placebo and were included in the modified intention-to-treat population. The four-component primary end point occurred in 105 of 428 patients (24.5%) assigned to receive levosimendan and in 103 of 421 (24.5%) assigned to receive placebo (adjusted odds ratio, 1.00; 99% confidence interval [CI], 0.66 to 1.54; P=0.98). The two-component primary end point occurred in 56 patients (13.1%) assigned to receive levosimendan and in 48 (11.4%) assigned to receive placebo (adjusted odds ratio, 1.18; 96% CI, 0.76 to 1.82; P=0.45). The rate of adverse events did not differ significantly between the two groups. Conclusions Prophylactic levosimendan did not result in a rate of the short-term composite end point of death, renal-replacement therapy, perioperative myocardial infarction, or use of a mechanical cardiac assist device that was lower than the rate with placebo among patients with a reduced left ventricular ejection fraction who were undergoing cardiac surgery with the use of cardiopulmonary bypass. (Funded by Tenax Therapeutics; LEVO-CTS number, NCT02025621 .).

Concepts: Clinical trial, Myocardial infarction, Cardiology, Heart failure, Ejection fraction, Heart, Randomness, Cardiac output


The birth of the intermittent injectate-based conventional pulmonary artery catheter (fondly nicknamed PAC) was proudly announced in the New England Journal of Medicine in 1970 by his parents HJ Swan and William Ganz. PAC grew rapidly, reaching manhood in 1986 where, in the US, he was shown to influence the management of over 40% of all ICU patients. His reputation, however, was tarnished in 1996 when Connors and colleagues suggested that he harmed patients. This was followed by randomized controlled trials demonstrating he was of little use. Furthermore, reports surfaced suggesting that he was unreliable and inaccurate. It also became clear that he was poorly understood and misinterpreted. Pretty soon after that, a posse of rivals (bedside echocardiography, pulse contour technology) moved into the neighborhood and claimed they could assess cardiac output more easily, less invasively and no less reliably. To make matter worse, dynamic assessment of fluid responsiveness (pulse pressure variation, stroke volume variation and leg raising) made a mockery of his ‘wedge’ pressure. While a handful of die-hard followers continued to promote his mission, the last few years of his existence were spent as a castaway until his death in 2013. His cousin (the continuous cardiac output PAC) continues to eke a living mostly in cardiac surgery patients who need central access anyway. This paper reviews the rise and fall of the conventional PAC.

Concepts: Lung, Cardiology, Heart, Randomized controlled trial, Blood pressure, Pulmonary artery, Cardiac output, Stroke volume


BACKGROUND: -Accurate measures are critical when attempting to distinguish normal from pathological changes in cardiac function during exercise, yet imaging modalities have seldom been assessed against invasive exercise standards. We sought to validate a novel method of biventricular volume quantification by cardiac magnetic resonance imaging (CMR) during maximal exercise. METHODS AND RESULTS: -CMR was performed on 34 subjects during exercise and free-breathing using an ungated real-time CMR (“RT-ungated”) sequence. ECG and respiratory movements were retrospectively synchronized enabling compensation for cardiac cycle and respiratory phase. Feasibility of RT-ungated imaging was compared with standard exercise CMR imaging with ECG gating (“gated”), Accuracy of RT-ungated CMR was assessed against an invasive standard (direct Fick) and reproducibility was determined following a second bout of maximal exercise. Ventricular volumes were able to be analyzed more frequently during high-intensity exercise using RT-ungated as compared with gated CMR (100% vs. 47%, p<0.0001) and with better inter-observer variability for RT-ungated (coefficient of variation CV=1.9% and 2.0% for left and right ventricular stroke volumes, respectively) than gated (CV=15.2% and 13.6%), p <0.01. Cardiac output determined by RT-ungated CMR proved accurate against the direct Fick method with excellent agreement (intraclass correlation coefficient R=0.96) which was highly reproducible during a second bout of maximal exercise (R=0.98). CONCLUSIONS: -By combining real-time ungated CMR with post-hoc analysis incorporating compensation for respiratory motion, highly reproducible and accurate biventricular volumes can be measured during maximal exercise.

Concepts: Scientific method, Cardiology, Heart, Nuclear magnetic resonance, Magnetic resonance imaging, Cardiac output, Covariance and correlation, Fick principle


Chronic chagasic cardiomyopathy (CCC) develops years after acute infection by Trypanosoma cruzi and does not improve after trypanocidal therapy, despite reduction of parasite burden. During disease, the heart undergoes oxidative stress, a potential causative factor for arrhythmias and contractile dysfunction. Here we tested whether antioxidants/ cardioprotective drugs could improve cardiac function in established Chagas heart disease. We chose a model that resembles B1-B2 stage of human CCC, treated mice with resveratrol and performed electrocardiography and echocardiography studies. Resveratrol reduced the prolonged PR and QTc intervals, increased heart rates and reversed sinus arrhythmia, atrial and atrioventricular conduction disorders; restored a normal left ventricular ejection fraction, improved stroke volume and cardiac output. Resveratrol activated the AMPK-pathway and reduced both ROS production and heart parasite burden, without interfering with vascularization or myocarditis intensity. Resveratrol was even capable of improving heart function of infected mice when treatment was started late after infection, while trypanocidal drug benznidazole failed. We attempted to mimic resveratrol’s actions using metformin (AMPK-activator) or tempol (SOD-mimetic). Metformin and tempol mimicked the beneficial effects of resveratrol on heart function and decreased lipid peroxidation, but did not alter parasite burden. These results indicate that AMPK activation and ROS neutralization are key strategies to induce tolerance to Chagas heart disease. Despite all tissue damage observed in established Chagas heart disease, we found that a physiological dysfunction can still be reversed by treatment with resveratrol, metformin and tempol, resulting in improved heart function and representing a starting point to develop innovative therapies in CCC.

Concepts: Blood, Myocardial infarction, Cardiology, Ejection fraction, Heart, Chagas disease, Heart disease, Cardiac output


In patients with acute circulatory failure, the decision to give fluids or not should not be taken lightly. The risk of overzealous fluid administration has been clearly established. Moreover, volume expansion does not always increase cardiac output as one expects. Thus, after the very initial phase and/or if fluid losses are not obvious, predicting fluid responsiveness should be the first step of fluid strategy. For this purpose, the central venous pressure as well as other “static” markers of preload has been used for decades, but they are not reliable. Robust evidence suggests that this traditional use should be abandoned. Over the last 15 years, a number of dynamic tests have been developed. These tests are based on the principle of inducing short-term changes in cardiac preload, using heart-lung interactions, the passive leg raise or by the infusion of small volumes of fluid, and to observe the resulting effect on cardiac output. Pulse pressure and stroke volume variations were first developed, but they are reliable only under strict conditions. The variations in vena caval diameters share many limitations of pulse pressure variations. The passive leg-raising test is now supported by solid evidence and is more frequently used. More recently, the end-expiratory occlusion test has been described, which is easily performed in ventilated patients. Unlike the traditional fluid challenge, these dynamic tests do not lead to fluid overload. The dynamic tests are complementary, and clinicians should choose between them based on the status of the patient and the cardiac output monitoring technique. Several methods and tests are currently available to identify preload responsiveness. All have some limitations, but they are frequently complementary. Along with elements indicating the risk of fluid administration, they should help clinicians to take the decision to administer fluids or not in a reasoned way.

Concepts: Blood, Cardiology, Heart, Volume, Blood pressure, Thermodynamics, Cardiac output, Mean arterial pressure


Purpose: To determine whether a carbohydrate mouth rinse can alter self-paced exercise performance independently of a high degree of thermal and cardiovascular strain. Methods: Eight endurance-trained males performed two 40-km cycling time trials in 35°C, 60% RH while swilling a 20-ml bolus of 6.5% maltodextrin (CHO) or a color- and taste-matched placebo (PLA) every 5 km. Heart rate, power output, rectal temperature (Tre), and mean skin temperature (Tsk) were recorded continuously; cardiac output, oxygen uptake (VO2), mean arterial pressure (MAP), and perceived exertion (RPE) were measured every 10 min. Results: Performance time and mean power output were similar between treatments, averaging 63.9 ± 3.2 and 64.3 ± 2.8 min, and 251 ± 23 and 242 ± 18 W in CHO and PLA, respectively. Power output, stroke volume, cardiac output, MAP, and VO2 decreased during both trials, increasing slightly or remaining stable during a final 2-km end-spurt. Tre, Tsk, heart rate, and RPE increased throughout exercise similarly with both treatments. Changes in RPE correlated with those in Tre (P < 0.005) and heart rate (P < 0.001). Conclusions: These findings suggest that carbohydrate mouth rinsing does not improve ~1-h time trial performance in hot-humid conditions, possibly due to a failure in down-regulating RPE, which may be influenced more by severe thermal and cardiovascular strain.

Concepts: Blood, Cardiology, Heart, Temperature, Artery, Cardiac output, Mean arterial pressure, Individual time trial


Transesophageal echocardiography (TEE) is increasingly replacing thermodilution pulmonary artery catheters to assess hemodynamics in patients at high risk for cardiovascular morbidity. However, one of the drawbacks of TEE compared to pulmonary artery catheters is the inability to measure real time stroke volume (SV) and cardiac output (CO) continuously. The aim of the present proof of concept study was to validate a novel method of SV estimation, based on pulse wave velocity (PWV) in patients undergoing cardiac surgery.

Concepts: Time, Blood, Lung, Cardiology, Heart, Echocardiography, Pulmonary artery, Cardiac output


Cardiovascular cine magnetic resonance (CMR) accelerated by compressed sensing (CS) is used to assess left ventricular (LV) function. However, it is difficult for prospective CS cine CMR to capture the complete end-diastolic phase, which can lead to underestimation of the end-diastolic volume (EDV), stroke volume (SV), and ejection fraction (EF), compared to retrospective standard cine CMR. This prospective study aimed to evaluate the diagnostic quality and accuracy of single-breath-hold full cardiac cycle CS cine CMR, acquired over two heart beats, to quantify LV volume in comparison to multi-breath-hold standard cine CMR.

Concepts: Blood, Evaluation, Cardiology, Heart, Cardiac output, Left ventricle, End-diastolic volume, Cardiovascular physiology


To prevent left ventricular dysfunction (LVD), surgery is recommended in patients with severe primary mitral regurgitation as soon as ejection fraction (EF) ≤60% or LV end-systolic diameter ≥40 mm. However, LVD may be concealed behind preoperative normal LVEF and LV end-systolic diameter. We sought to identify whether a new composite echocardiographic Doppler marker of the LV ejection according to the LV dilatation may predict postoperative LVD and outcome after mitral valve repair in patients with primary mitral regurgitation.

Concepts: Cardiology, Ejection fraction, Echocardiography, Cardiac output, Mitral valve, Mitral regurgitation, Mitral valve prolapse, Mitral valve repair


The use of cardiac output monitoring to guide intra-venous fluid and inotropic therapies may improve peri-operative outcomes, but uncertainty exists regarding clinical effectiveness and robust cost-effectiveness evidence is lacking. The objective of the study was to evaluate the cost-effectiveness of peri-operative cardiac output-guided haemodynamic therapy versus usual care in high-risk patients undergoing major gastrointestinal surgery.

Concepts: Medicine, Clinical trial, Avicenna, Therapy, Intravenous therapy, Cardiac output, Therapy?, Routes of administration