Natalia Briceno

Ischaemic cardiomyopathy: pathophysiology, assessment and the role of revascularisation

### Learning objectives Ischaemic heart disease (IHD) continues to be the most common cause of death globally according to WHO and is the most common cause of heart failure in the developed world.1–4 Heart failure secondary to IHD has been shown to be independently associated with mortality compared with a non-ischaemic aetiology.5 ,6 The increasing incidence has been attributed to the success of thrombolytic and primary percutaneous coronary intervention in acute myocardial infarctions, leading to improved patient survival, however often leading to increased morbidity due to left ventricular (LV) remodelling and chronic myocardial dysfunction. The term ischaemic cardiomyopathy (ICM) has been defined as LV systolic dysfunction with one or more of the following: a history of prior myocardial revascularisation or myocardial infarction, more than 75% stenosis in the left main stem or left anterior descending artery, or two vessels or more with a greater than 75% stenosis.7 There are multiple mechanisms attributed to the development of ICM including mechanical and neurohormonal factors,8 however the pathophysiological concept of myocardial hibernation has been of particular interest for several decades. Rahimtoola in the 1980s was one of the first to propose the term myocardial hibernation following the observation that patients with LV dysfunction recovered function following surgical revascularisation.9 ,10 Hibernating myocardium is a retrospective definition based upon the evidence of functional recovery following revascularisation.11 It is thought to be an adaptive process to repetitive ischaemia secondary to chronically reduced myocardial blood flow and reduced coronary flow reserve, whereby a loss in contractile apparatus results in …

Percutaneous mechanical circulatory support: current concepts and future directions

### Learning objectives Percutaneous mechanical circulatory support (MCS) strategies have been in the clinical arena for approximately half a century, with the main aim of providing adequate systemic tissue perfusion, while also favourably impacting myocardial oxygen supply and demand, to optimise myocardial recovery in the face of cardiogenic shock (CS). This can be in the context of acute haemodynamic instability following a myocardial insult such as an acute coronary syndrome or myocarditis, or acute decompensation in a patient with chronic heart failure due to varying aetiologies. Despite major advances in both pharmacological and interventional therapies, CS continues to have a very poor prognosis with mortality rates in the order of 40%–80%.1–3 In addition to CS, MCS is more commonly being considered for patients with chronic heart failure undergoing high-risk percutaneous coronary intervention (PCI). This increasing population of ischaemic heart failure patients is due in part to improving survival after acute myocardial infarction (AMI), but with persistent myocardial damage despite timely reperfusion.4 In the setting of haemodynamic collapse, inotropes and vasopressors are often started immediately, due to their rapid onset of action. Although they differ in terms of their effects on systemic vascular resistance, these agents increase myocardial oxygen demand through their impact on adrenergic pathways.5 ,6 As a result, pharmacologic support can worsen mortality in CS and hence should only be used as a short-term means to achieve haemodynamic stability. In contrast to drug therapy, percutaneous MCS reduces myocardial …

Is there benefit in implanting defibrillators in patients with severe heart failure

Background It is current practice to withhold implantable cardioverter defibrillators (ICD) from patients with severe heart failure because their deaths are judged as non-sudden and therefore assumed not to be preventable by ICD. If this was true, there should be a trend towards reduced preventability of deaths in the severe heart failure subgroups within existing randomised control ICD trials. We tested the prevailing assumption that patients with most severe heart failure would not benefit from ICD implantation. Methods Six trials were identified enrolling 7873 patients, with 2734 patients randomly assigned to receive an ICD. Reduction in mortality in the ICD arm varied between 5.6% and 31%. All six trials provided data separated into higher and lower ejection fraction subgroups. Five trials provided data separated into higher and lower New York Heart Association (NYHA) class patient subgroups. Results For patients subcategorised by NYHA class, there was a non-significant difference in z-score (p=0.922) between patients with mild to moderate and severe heart failure. Similarly, subgrouping by left ventricular ejection fraction (LVEF) revealed no significant difference between z-scores (p=0.170). Both observations suggest no attenuation of benefit of ICD implantation in patients with higher NYHA class or lower LVEF. Conclusion There is no evidence within the existing trial populations of a tendency for the relative risk reduction to be smaller in patients with severe heart failure. The prevailing assumption that severe heart failure patients are less likely to benefit from ICD therapy must be questioned.

18 Baseline coronary flow varies with normal cardiac catheter laboratory stimuli

Introduction Fractional Flow Reserve (FFR) is a pressure-derived estimate of coronary flow impairment during maximal and constant hyperaemia provided by an adenosine infusion, when flow and pressure approximate linearly. The need for adenosine-induced hyperaemia has led to development of a stenosis severity index measured at rest, Instantaneous Wave Free Ratio (iFR). Its use and proposed applicability to serial/diffuse disease has relied on assumptions that coronary flow at rest is maintained at constant levels. This study aimed to assess variability of resting coronary flow with normal Catheter laboratory stimuli. Methods Forty-Seven elective patients were recruited with a variety of coronary artery disease severity (mean FFR: 0.883; SD: 0.938). Simultaneous intracoronary pressure (Pd) and Doppler Average Peak Flow Velocity, APV(U), recordings were made. These were made both at rest and just prior to supine bicycle exercise or intravenous adenosine infusion. Results Average peak flow velocity varied significantly between measurements at rest and just prior to commencement of adenosine or supine bicycle exercise (18.1765cm/s vs. 19.4689cm/s, p 0.002). This was without significant change in haemodynamics (Table 1). Conclusion Resting coronary flow appears to vary significantly with normal Catheter Laboratory stimuli, such as simple warnings, irrespective of haemodynamic status. Abstract 18 Table 1 Table illustrating changes in Heart Rate, Systolic Blood Pressure (SBP), Ratio of distal coronary pressure to proximal aortic pressure (Pd/Pa) and Average Peak Coronary Flow Velocity (APV) Mean Std. Deviation Resting HR 80.149 14.7780 Pre Stress HR 82.468 (p: 0.227) 15.9208 Resting SBP 128.23 20.6944 Pre Stress SBP 128.88 (p: 0577) 22.9778 Resting Pd/Pa 0.9307 0.1106 Pre Stress Pd/Pa 0.9370 (p: 0.089) 0.1120 Resting APV (U) 18.1765 7.4892 Pre Stress APV (U) 19.4689 (p: 0.002) 7.7007

Changes in contractility determine coronary haemodynamics in dyssynchronous left ventricular heart failure, not vice versa

Background Biventricular pacing has been shown to increase both cardiac contractility and coronary flow acutely but the causal relationship is unclear. We hypothesised that changes in coronary flow are secondary to changes in cardiac contractility. We sought to examine this relationship by modulating coronary flow and cardiac contractility. Methods Contractility and lusitropy were altered by varying the location of pacing in 8 patients. Coronary autoregulation was transiently disabled with intracoronary adenosine. Simultaneous coronary flow velocity, coronary pressure and left ventricular pressure data were measured in the different pacing settings with and without hyperaemia and wave intensity analysis performed. Results Multisite pacing was effective at altering left ventricular contractility and lusitropy (pos. dp/dtmax −13% to +10% and neg. dp/dtmax −15% to +17% compared to baseline). Intracoronary adenosine decreased microvascular resistance (362.5 mm Hg/s/m to 156.7 mm Hg/s/m, p < 0.001) and increased LAD flow velocity (22 cm/s vs 45 cm/s, p < 0.001) but did not acutely change contractility or lusitropy. The magnitude of the dominant accelerating wave, the Backward Expansion Wave, was proportional to the degree of contractility as well as lusitropy (r = 0.47, p < 0.01 and r = −0.50, p < 0.01). Perfusion efficiency (the proportion of accelerating waves) increased at hyperaemia (76% rest vs 81% hyperaemia, p = 0.04). Perfusion efficiency correlated with contractility and lusitropy at rest (r = 0.43 & −0.50 respectively, p = 0.01) and hyperaemia (r = 0.59 & −0.6, p < 0.01). Conclusions Acutely increasing coronary flow with adenosine in patients with systolic heart failure does not increase contractility. Changes in coronary flow with biventricular pacing are likely to be a consequence of enhanced cardiac contractility from resynchronization and not vice versa.

Cardiac Arrest in Acute Myocardial Infarction: Concept of Circulatory Support With Mechanical Chest Compression and Impella to Facilitate Percutaneous Coronary Intervention

Cardiogenic shock in the context of acute ST-elevation myocardial infarction (STEMI) remains a challenge to manage and results in significant mortality and morbidity, cardiac arrest in this setting even more so. The increase in myocardial oxygen demand and consumption with the use of inotropes is recognised as increasing mortality. Alternatives include the intra-aortic balloon pump (IABP), which has yet to be shown to improve outcomes, and extracorporeal membrane oxygenation (ECMO), which requires super-specialised techniques not widely available. We report a case of Anterior STEMI from a left main stem occlusion suffering with cardiac arrest on reaching the catheter laboratory table necessitating external mechanical compression with an Autopulse™. The patient remained in pulseless electrical activity (PEA) throughout, and was Autopulse dependent despite successful percutaneous coronary intervention (PCI). An Impella® was inserted for additional mechanical support and facilitated successful weaning from cardiopulmonary resuscitation (CPR). Despite 105minutes without a spontaneous output, we describe the first documented case of simultaneous use of Impella with mechanical CPR with a successful outcome; demonstrating a potential technique of good mechanical haemodynamic support to aide early revascularisation that may have potential utility in the treatment of cardiogenic shock and arrest.

Use of novel intracoronary technology to investigate the effect of cold air inhalation during exercise on coronary microvascular resistance and blood flow in coronary artery disease: a cross-sectional study

Abstract Background Highest rates of exertion-related cardiac death occur during cold air inhalation (eg, shovelling snow), but the pathophysiological changes are unclear. Novel technology with intracoronary wires simultaneously and accurately measures coronary artery pressure and coronary blood flow, allowing physiological investigation of the effects of cold air during exercise. We explored the effects of exercise with and without cold air on coronary microvascular resistance and coronary blood flow in patients with coronary artery disease. Methods Patients with severe coronary artery stenoses undergoing coronary angiography were allocated to 5 min of cold air inhalation (–15°C), exercise (incremental supine ergometry), or exercise with cold air. We used two-way ANOVA to compare rest and peak measurements of coronary blood flow and microvascular resistance. We also used wave intensity analysis to identify waves that accelerate and decelerate coronary blood flow, and calculated the proportional contribution of accelerating waves as a coronary perfusion efficiency index. Findings We recruited 39 patients (mean 62 years [SD 9]), obtaining 51 datasets (14 cold air alone, 24 exercise, 13 exercise with cold air). 12 patients were in both the exercise and exercise with cold air groups, and for these patients the order was randomised. Microvascular resistance increased during cold air alone (558 mm Hg/cm per s [133] at rest vs 655 [221] at peak, p=0·04), and decreased during exercise (579 [192] vs 431 [166], p vs 495 [150]). The increase in coronary blood flow was similarly 34% less during exercise with cold air (19·3 cm/s [7·4] at rest vs 26·0 [10·7] at peak, p=0·04) than without (18·8 [7·3] vs 28·4 [11·3], p=0·04). An increase in coronary perfusion efficiency during exercise (69·8% [12·0] at rest vs 77·7 [9·2] at peak, p=0·05) was abolished with the addition of cold air during exercise (70·3 [10·7] vs 69·3 [10·0]). Interpretation We provide the first evidence, to our knowledge, that cold air substantially attenuates the reduction in microvascular resistance and the increase in coronary blood flow that normally occur during exercise. Moreover, although the heart has improved coronary perfusion efficiency during exercise, it can be reduced when combined with cold air. This finding suggests that cold air during exercise can impede coronary vasodilatation and ventricular relaxation, rendering the heart more susceptible to ischaemia. Funding British Heart Foundation, National Institute for Health Research.

30 Head-to-Head Comparison of Two Novel Indices of Microcirculatory Resistance at Predicting Microvascular Dysfunction. Use of the Best Index to Explore the Effect of Cold Air Inhalation During Exercise in Coronary Artery Disease Patients

Introduction Highest rates of exertion related cardiac death occur during cold air inhalation (CAI): e.g. shovelling snow, but the pathophysiology is unclear. Novel intracoronary wires that simultaneously measure arterial pressure (Pd) and blood flow (CBF) allow quantification of coronary micro-vascular resistance (MVR). A. We compared the accuracy of Doppler-derived hyperemic micro-vascular resistance (hMR) and thermodilution-derived index of microcirculatory resistance (IMR) at predicting micro-vascular dysfunction, as there is no current invasive gold-standard measurement of MVR. B. In coronary artery disease (CAD) patients we explored the effects of exercise with and without CAI on MVR (using the most accurate measure from A.) and CBF. Methods A. 56 patients (61+/-10 years) undergoing cardiac catheterization for stable CAD or acute myocardial infarction (AMI) were recruited. Simultaneous intracoronary pressure, Doppler flow velocity and thermodilution were carried out in 74 unobstructed vessels, at rest and during hyperemia. Three independent measures of micro-vascular function were assessed, using predefined dichotomous thresholds: 1) CFRmean, the average value of Doppler- and thermodilution-derived coronary flow reserve (CFR), and cardiovascular magnetic resonance derived 2) Myocardial Perfusion Reserve Index (MPRI) and 3) Micro-vascular Obstruction (MVO). B. 35 CAD patients (61+/-9 years) undertook 5 min of either: CAI (-15oC) Exercise (Incremental supine ergometry) Exercise with CAI. We measured baseline and peak MVR (Pd/CBF) and CBF, and calculated the proportional contribution of waves that accelerate versus decelerate CBF as a coronary perfusion efficiency index. Results A. hMR had better diagnostic accuracy than IMR to predict CFRmean (area under curve, (AUC) 0.82 vs. 0.58, p < 0.001, sensitivity/specificity 77/77% vs. 51/71%) and MPRI (AUC 0.85 vs. 0.72, p = 0.19, sensitivity/specificity 82/80% vs. 64/75%). In AMI patients, the AUCs of hMR and IMR at predicting MVO were 0.83 and 0.72 respectively (p = 0.22, sensitivity/specificity 78/74% vs. 44/91%).Abstract 30 Figure 1 Defining best measure of microvascular resistance B. 47 datasets were obtained: n = 10 n = 24 n = 13. (12 patients did both conditions 2 and 3, in randomized order). MVR increased during CAI alone (p = 0.04), and decreased during exercise (p < 0.0001). Exercise with CAI was associated with less decrease in MVR (NS). The increase in CBF was similarly 34% less during exercise with CAI (p = 0.04) versus without (p < 0.0001). Coronary perfusion efficiency increased during exercise (p < 0.05), but CAI during exercise abolished this.Abstract 30 Figure 2 Simultaneous measurement of microvascular resistance during cold air inhalation and exercise Conclusions A. Doppler-derived hMR may have superior diagnostic accuracy than IMR at predicting invasive and non-invasive measures of micro-vascular function. B. CAI attenuates the reduction in MVR and the increases in CBF and coronary perfusion efficiency that normally occur during exercise. These suggest impedance of coronary vasodilatation and ventricular relaxation, rendering the heart more susceptible to ischaemia.

1 Why is cold air associated with increased susceptibility to myocardial ischaemia

Introduction Cold air inhalation (CAI) during exercise increases cardiac mortality. The pathophysiology remains unclear, but may reflect adverse changes in microvascular resistance (MVR). We compared the accuracy of two novel intra-coronary measures of MVR to predict microvascular dysfunction (MVD). We then used the best MVR measure to quantify changes during CAI, exercise alone and exercise with CAI. Methods 56 patients (74 arteries: post PCI or FFR >0.8) had hyperaemic microvascular resistance (hMR) and index of microcirculatory resistance (IMR) compared against: Coronary flow reserve (CFR) CMR perfusion CMR microvascular obstruction (MVO). In a further 55 patients (45 with coronary artery disease (CAD), baseline and peak MVR was measured after 5 min of either: CAI (-15oC) Cycling CAI during cycling. Results hMR had better diagnostic accuracy than IMR to predict CFR (AUC 0.82 vs. 0.58), CMR perfusion (AUC 0.85 vs. 0.72) and MVO (AUC 0.83 vs. 0.72) (Figure 1, Study 1). CAI at rest decreased MVR in patients with normal coronaries but increased MVR in CAD patients (p < 0.01) (Figure 1, Study 2). In CAD patients, cycling caused an adaptive decrease in MVR (p < 0.0001), but CAI during cycling abolished this decrease (Figure 1, Study 2). Conclusions hMR is a better predictor of MVD than IMR. CAI causes adverse changes in MVR in CAD patients both at rest and during exercise, rendering the heart more susceptible to ischaemia. Abstract 1 Figure 1 Investigation of best invasive measure of microvascular resistance (Study 1), and its application during cold air inhalation (CAI) at rest, and during exercise (Study 2)

To Revascularise or Not To Revascularise, That Is the Question: the Diagnostic and Management Conundrum of Ischaemic Cardiomyopathy

Ischaemic cardiomyopathy is an important cardiovascular condition that has differing pathophysiological substrates and clinical manifestations. Contemporary management involves the administration of heart failure pharmacotherapy and device therapy where indicated, which has good prognostic data to support it. Whilst the role of revascularisation is clear in those patients presenting with an acute coronary syndrome or angina, the role in those patients presenting either incidentally, with predominant heart failure symptoms, or in those presenting with acute heart failure with an associated elevated troponin is less well defined and lacks randomised outcome data to support its adoption. The aim of this review is therefore to discuss the challenges in the diagnosis of ischaemic cardiomyopathy with a review of the existing imaging modalities that can facilitate, and to revisit the variety of clinical presentations that can occur, with particular emphasis on the contemporary role of revascularisation in these cohorts of patients.