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Heartbeat: oxygen transport close to and far from the ventricle in heart failure
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  1. Catherine M Otto
  1. Division of Cardiology, University of Washington, Seattle, WA 98195, USA
  1. Correspondence to Professor Catherine M Otto, Division of Cardiology, University of Washington, Seattle, WA 98195, USA; cmotto{at}uw.edu

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In patients with heart failure with reduced ejection fraction, impaired oxygen delivery to peripheral muscles is blunted due to left ventricular systolic dysfunction with a reduced stroke volume reserve during exercise. Hearon and colleagues1 hypothesised that patients with heart failure with preserved ejection fraction (HFpEF) also might have impaired oxygen delivery and utilisation (V02 kinetics) in response to increased skeletal muscle metabolic demands during exercise. In a series of 19 patients with HFpEF, compared to 18 control subjects, there were markedly slower rates of maximal oxygen utilisation due to impaired peripheral oxygen extraction, despite a normal increase in submaximal cardiac output with exercise (figure 1). The authors suggest that impaired peripheral oxygen utilisation might be a target for therapy in patients with HFpEF.

Figure 1

(A) Representative breath-by-breath ventilatory oxygen uptake kinetics in a HFpEF patient (blue) and a healthy control subject (black). Breath-by-breath oxygen utilisation (V̇O2) was measured during submaximal treadmill exercise, interpolated linearly at 1 s intervals and fitted using on-transient monoexponential curve fitting. (B) Mean response curves for controls HFpEF patients and HFpEF patients stratified by mean response time (MRT) modelled using group average amplitude (Δ V̇O2=steady state V̇O2 – baseline V̇O2) and MRT, defined as the exponential time constant of V̇O2 onset kinetics, which reflects the time needed for oxygen uptake to rise to~63% of steady state V̇O2. HFpEF, heart failure with preserved ejection fraction.

In the aptly titled editorial ‘Package delivered, message not received’, Borlaug2 concludes that ‘there are many steps in the O2 transport pathway that become compromised in people with HFpEF. Hearon and colleagues1 have reminded us how the final steps in this pathway are often just as limiting as the more central steps closer to the heart, and in the process, they have elegantly demonstrated how we may be able to use VO2 kinetics to help identify the patients where these peripheral steps become most compromised (figure 2). If the mail is not being delivered, we need to know why, and the same is true if O2 transport is constrained. It is hoped that with more robust phenotyping methods, using VO2 kinetics and other novel methods, we will one day be in a position to better understand the nature of deficits in both the heart and periphery at the individual patient level, enabling better tailoring of therapies to improve clinical status for this large and ever expanding cohort’.

Figure 2

Schematic representation of oxygen consumption (VO2) kinetics. VO2 (red line) is plotted as a function of time during constant workload exercise. The mean response time (MRT) represents the time required for VO2 to rise to ~63% of steady-state level at a given exercise workload. In health, VO2 rises very rapidly during exercise, because both the convective and diffusive components of the O2 transport pathway are able to respond rapidly and efficiently to increasing metabolic demand, with a pattern that more closely resembles an idealised square wave (upper left bounds). In patients with abnormal VO2 kinetics, there is a progressive lag in the increase in VO2, resulting in prolongation of the MRT and an increase in the gap between the square wave and the observed increase in VO2 (red shaded area). This gap is termed the oxygen deficit, and may be caused by convective or diffusive abnormalities in O2 transport.

The diagnosis of acute myocardial infarction (AMI) can be challenging in patients with a left bundle branch block (LBBB) on electrocardiography. Nestelberger and colleagues3 examined the diagnostic performance of ECG criteria and high-sensitivity cardiac troponin (hs-cTn) compared with a centrally adjudicated diagnosis of AMI using the universal definition of myocardial infarction in a series of almost 9000 patients who presented with chest pain. A LBBB was present in <3% of patients and only 30% of these patients had an AMI, with no difference between those with a new or known LBBB. In patients with LBBB, ECG criteria alone were specific (95%–100%), but not sensitive 1%–12%), for diagnosis of AMI. In contrast, a diagnostic algorithm (figure 3) combining ECG criteria with hs-cTn levels at baseline and the change in levels at 1–2 hours, had a high accuracy (97%) for diagnosis of AMI in patients with LBBB.

Figure 3

Integrated diagnostic work-up in cohort 1. Flow chart representing the integrated diagnostic work-up for patients presenting with left bundle branch block and suspected AMI in cohort one using hs-cTnT. AMI, acute myocardial infarction; hs-cTn, high-sensitivity cardiac troponin; CPO, chest pain onset; LBBB, left bundle branch block; pts, patients.

In an editorial, Glass et al 4 find these results encouraging but caution that ‘these data are limited to patients with suspected AMI due to acute coronary occlusion; at the present time, the algorithm cannot be extrapolated to patients presenting with other possible aetiologies for hs-cTn elevation (eg, troponin elevations due to demand ischaemia, sepsis or renal insufficiency)—this issue is the major limitation of this algorithm. Additionally, in patients with LBBB but without ECG changes diagnostic of AMI, negative hs-cTn determinations should not be construed to preclude the need for further evaluation or treatment of alternative, non-AMI causes of chest pain (eg, unstable angina, pulmonary embolism and so on)’.

Coronary microvascular dysfunction (CMD) increasingly is recognised as a cause of symptoms and predictor of adverse cardiovascular events in the 40% of patients undergoing coronary angiography who are found to have normal vessels or non-obstructive coronary disease. In a comprehensive review article, Rahman and colleagues5 summarise the diagnostic and therapeutic approach to these patients and point out the knowledge gaps needing further clinical research (figure 4).

Figure 4

Comprehensive assessment of NOCAD during the time of angiography. *Evaluation of atheromatous disease can be carried out using resting or submaximal hyperaemic indices based on local practice. §Patients with visible atheroma should be commenced on secondary preventative therapy regardless of final diagnosis. The white area describes tests available on an ad hoc basis in all catheter laboratories, whereas the grey shaded area describes acetylcholine testing that can currently only be performed on a named-patient basis clinically, or within the context of dedicated research protocols, limiting its widespread ad hoc use. CAD, coronary artery disease; CFR, coronary flow reserve; CMD, coronary microvascular dysfunction; FFR, fractional flow reserve; NOCAD, non-obstructive coronary artery disease.

Other interesting content in this issue includes a review of the clinical presentation and management of pregnancy in women with cardiomyopathy,6 the Education in Heart article on cardiac computed tomographic (CT) imaging (figure 5)7 and the Image Challenge8 case which uses imaging findings to make the diagnosis in 62 year old women with non-sustained ventricular tachycardia.

Figure 5

An illustration of the application of CCTA for the detection and evaluation of coronary artery disease. Panel A shows a multiplanar reformatted image of the left anterior descending artery illustrating the use of CCTA for detection of CAD in either symptomatic or high-risk asymptomatic individuals. Panel B shows the use of CCTA to evaluate plaque characteristics (ie, degree of calcification) and presence of high-risk findings (in this instance, positive remodelling). Panel C shows the use of CCTA for quantitative plaque assessment while panel D shows the use of CTP for the assessment of coronary physiology in the setting of coronary artery disease. CCTA, coronary CT angiography; CTP, CT perfusion.

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Footnotes

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Commissioned; internally peer reviewed.

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