Matthew Lumley

Long-Term Mortality Data From the Balloon Pump–Assisted Coronary Intervention Study (BCIS-1) A Randomized, Controlled Trial of Elective Balloon Counterpulsation During High-Risk Percutaneous Coronary Intervention

Background— There is conflicting evidence on the utility of elective intra-aortic balloon pump (IABP) use during high-risk percutaneous coronary intervention (PCI). Observational series have indicated a reduction in major in-hospital adverse events, although randomized trial evidence does not support this. A recent study has suggested a mortality benefit trend early after PCI, but there are currently no long-term outcome data from randomized trials in this setting. Methods and Results— Three hundred one patients with left ventricular impairment (ejection fraction <30%) and severe coronary disease (BCIS-1 jeopardy score ≥8; maximum possible score=12) were randomized to receive PCI with elective IABP support (n=151) or without planned IABP support (n=150). Long-term all-cause mortality was assessed by tracking the databases held at the Office of National Statistics (in England and Wales) and the General Register Office (in Scotland). The groups were balanced in terms of baseline characteristics (left ventricular ejection fraction, 23.6%; BCIS-1 jeopardy score, 10.4) and the amount and type of revascularization performed. Mortality data were available for the entire cohort at a median of 51 months (interquartile range, 41–58) from randomization. All-cause mortality at follow-up was 33% in the overall cohort, with significantly fewer deaths occurring in the elective IABP group (n=42) than in the group that underwent PCI without planned IABP support (n=58) (hazard ratio, 0.66; 95% confidence interval, 0.44–0.98; P=0.039). Conclusions— In patients with severe ischemic cardiomyopathy treated with PCI, all-cause mortality was 33% at a median of 51 months. Elective IABP use during PCI was associated with a 34% relative reduction in all-cause mortality compared with unsupported PCI. Clinical Trial Registration— URL: http://www.isrctn.org. Unique identifier: ISRCTN40553718; and http://www.clinicaltrials.gov. Unique identifier: NCT00910481.

Coronary and Microvascular Physiology During Intra-Aortic Balloon Counterpulsation

OBJECTIVES This study sought to identify the effect of coronary autoregulation on myocardial perfusion during intra-aortic balloon pump (IABP) therapy. BACKGROUND IABP is the most commonly used circulatory support device, although its efficacy in certain scenarios has been questioned. The impact of alterations in microvascular function on IABP efficacy has not previously been evaluated in humans. METHODS Thirteen patients with ischemic cardiomyopathy (left ventricular ejection fraction: 34 ± 8%) undergoing percutaneous coronary intervention were recruited. Simultaneous intracoronary pressure and Doppler-flow measurements were undertaken in the target vessel following percutaneous coronary intervention, during unassisted and IABP-assisted conditions. Coronary autoregulation was modulated by the use of intracoronary adenosine, inducing maximal hyperemia. Wave intensity analysis characterized the coronary wave energies associated with balloon counterpulsation. RESULTS Two unique diastolic coronary waves were temporally associated with IABP device use; a forward compression wave and a forward expansion wave caused by inflation and deflation, respectively. During basal conditions, IABP therapy increased distal coronary pressure (82.4 ± 16.1 vs. 88.7 ± 17.8 mm Hg, p = 0.03), as well as microvascular resistance (2.32 ± 0.52 vs. 3.27 ± 0.41 mm Hg cm s(-1), p = 0.001), with no change in average peak velocity (30.6 ± 12.0 vs. 26.6 ± 11.3 cm s(-1), p = 0.59). When autoregulation was disabled, counterpulsation caused an increase in average peak velocity (39.4 ± 10.5 vs. 44.7 ± 17.5 cm s(-1), p = 0.002) that was linearly related with IABP-forward compression wave energy (R(2) = 0.71, p = 0.001). CONCLUSIONS Autoregulation ameliorates the effect of IABP on coronary flow. However, during hyperemia, IABP augments myocardial perfusion, principally due to a diastolic forward compression wave caused by balloon inflation, suggesting IABP would be of greatest benefit when microcirculatory reserve is exhausted.

Intra-aortic Balloon Pump Trials Questions, Answers, and Unresolved Issues

Clinical experience with the intra-aortic balloon pump (IABP) spans >40 years.1 Physiological studies have demonstrated that the IABP acutely improves systemic hemodynamics, augments coronary flow, reduces myocardial oxygen demand, and can sustain coronary patency after percutaneous revascularization.2–4 These sound physiological principles, largely supportive observational data,5–7 and a historical lack of alternative percutaneous devices to provide circulatory support led to the widespread use of the IABP in cardiogenic shock secondary to acute myocardial infarction (AMI), ST-segment elevation-acute coronary syndrome without shock and also in high-risk percutaneous coronary intervention (PCI), despite a paucity of adequately powered randomized evidence to support their use. Nearly 5 decades since the introduction of IABP into clinical practice, we finally have randomized data on the efficacy of balloon counterpulsation for each of the 3 above indications.8–10 The main clinical applications for counterpulsation and the randomized data for each indication are summarized in the Table. View this table: Table. Randomized Control Trials of Intra-aortic Balloon Counterpulsation To the surprise of many who have come to rely on the support and reassurance provided by this device, none of the recent trials reached their primary efficacy end points. Where does that leave us with the IABP? Is it time to abandon ship or is there hope yet for an old friend? Perhaps the most surprising of these randomized controlled trial (RCT) results was from the most recent trial, IABP-SHOCK II.8 This multicenter, open-labeled, randomized study enrolled 600 patients with AMI (with or without ST-segment elevation) with cardiogenic shock, if early revascularization was planned. Patients were randomized in a 1:1 ratio to intra-aortic balloon counterpulsation (IABP group) or no intra-aortic counterpulsation (control group). The primary study end point, 30-day all-cause mortality, occurred in a similar proportion of the IABP and control groups (39.7% …

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 …

Physiology of Angina and its Alleviation with Nitroglycerine- Insights from Invasive Catheter Laboratory Measurements During Exercise

Background: The mechanisms governing exercise-induced angina and its alleviation by the most commonly used antianginal drug, nitroglycerin, are incompletely understood. The purpose of this study was to develop a method by which the effects of antianginal drugs could be evaluated invasively during physiological exercise to gain further understanding of the clinical impact of angina and nitroglycerin. Methods: Forty patients (mean age, 65.2±7.6 years) with exertional angina and coronary artery disease underwent cardiac catheterization via radial access and performed incremental exercise using a supine cycle ergometer. As they developed limiting angina, sublingual nitroglycerin was administered to half the patients, and all patients continued to exercise for 2 minutes at the same workload. Throughout exercise, distal coronary pressure and flow velocity and central aortic pressure were recorded with sensor wires. Results: Patients continued to exercise after nitroglycerin administration with less ST-segment depression (P=0.003) and therefore myocardial ischemia. Significant reductions in afterload (aortic pressure, P=0.030) and myocardial oxygen demand were seen (tension-time index, P=0.024; rate-pressure product, P=0.046), as well as an increase in myocardial oxygen supply (Buckberg index, P=0.017). Exercise reduced peripheral arterial wave reflection (P<0.05), which was not further augmented by the administration of nitroglycerin (P=0.648). The observed increases in coronary pressure gradient, stenosis resistance, and flow velocity did not reach statistical significance; however, the diastolic velocity–pressure gradient relation was consistent with a significant increase in relative stenosis severity (k coefficient, P<0.0001), in keeping with exercise-induced vasoconstriction of stenosed epicardial segments and dilatation of normal segments, with trends toward reversal with nitroglycerin. Conclusions: The catheterization laboratory protocol provides a model to study myocardial ischemia and the actions of novel and established antianginal drugs. Administration of nitroglycerin causes changes in the systemic and coronary circulation that combine to reduce myocardial oxygen demand and to increase supply, thereby attenuating exercise-induced ischemia. Designing antianginal therapies that exploit these mechanisms may provide new therapeutic strategies.

Doppler Versus Thermodilution-Derived Coronary Microvascular Resistance to Predict Coronary Microvascular Dysfunction in Patients With Acute Myocardial Infarction or Stable Angina Pectoris

Coronary microvascular resistance is increasingly measured as a predictor of clinical outcomes, but there is no accepted gold-standard measurement. We compared the diagnostic accuracy of 2 invasive indices of microvascular resistance, Doppler-derived hyperemic microvascular resistance (hMR) and thermodilution-derived index of microcirculatory resistance (IMR), at predicting microvascular dysfunction. A total of 54 patients (61 ± 10 years) who underwent cardiac catheterization for stable coronary artery disease (n = 10) or acute myocardial infarction (n = 44) had simultaneous intracoronary pressure, Doppler flow velocity and thermodilution flow data acquired from 74 unobstructed vessels, at rest and during hyperemia. Three independent measurements of microvascular function were assessed, using predefined dichotomous thresholds: (1) coronary flow reserve (CFR), the average value of Doppler- and thermodilution-derived CFR; (2) cardiovascular magnetic resonance (CMR) derived myocardial perfusion reserve index; and (3) CMR-derived microvascular obstruction. hMR correlated with IMR (rho = 0.41, p <0.0001). hMR had better diagnostic accuracy than IMR to predict CFR (area under curve [AUC] 0.82 vs 0.58, p <0.001, sensitivity and specificity 77% and 77% vs 51% and 71%) and myocardial perfusion reserve index (AUC 0.85 vs 0.72, p = 0.19, sensitivity and specificity 82% and 80% vs 64% and 75%). In patients with acute myocardial infarction, the AUCs of hMR and IMR at predicting extensive microvascular obstruction were 0.83 and 0.72, respectively (p = 0.22, sensitivity and specificity 78% and 74% vs 44% and 91%). We conclude that these 2 invasive indices of coronary microvascular resistance only correlate modestly and so cannot be considered equivalent. In our study, the correlation between independent invasive and noninvasive measurements of microvascular function was better with hMR than with IMR.

Effects of Epicardial and Endocardial Cardiac Resynchronization Therapy on Coronary Flow: Insights From Wave Intensity Analysis.

Background The increase in global coronary flow seen with conventional biventricular pacing is mediated by an increase in the dominant backward expansion wave (BEW). Little is known about the determinants of flow in the left‐sided epicardial coronary arteries beyond this or the effect of endocardial pacing stimulation on coronary physiology. Methods and Results Eleven patients with a chronically implanted biventricular pacemaker underwent an acute hemodynamic and electrophysiological study. Five of 11 patients also took part in a left ventricular endocardial pacing protocol at the same time. Conventional biventricular pacing, delivered epicardially from the coronary sinus, resulted in a 9% increase in flow (average peak velocity) in the left anterior descending artery (LAD), mediated by a 13% increase in the area under the BEW (P=0.004). Endocardial pacing resulted in a 27% increase in LAD flow, mediated by a 112% increase in the area under the forward compression wave (FCW) and a 43% increase in the area under the BEW (P=0.048 and P=0.036, respectively). There were no significant changes in circumflex parameters. Conventional biventricular pacing resulted in homogenization of timing of coronary flow compared with baseline (mean difference in time to peak in the LAD versus circumflex artery: FCW 39 ms [baseline] versus 3 ms [conventional biventricular pacing], P=0.008; BEW 47 ms [baseline] versus 8 ms [conventional biventricular pacing], P=0.004). Conclusions Epicardial and endocardial pacing result in increased coronary flow in the left anterior descending artery and homogenization of the timing of waves that determine flow in the LAD and the circumflex artery. The increase in both the FCW and the BEW with endocardial pacing may be the result of a more physiological activation pattern than that of epicardial pacing, which resulted in an increase of only the BEW.

Intraaortic balloon pump use in high-risk percutaneous coronary intervention.

Purpose of review Despite the long-term availability and clinical usage of intraaortic balloon pump (IABP) counterpulsation, there is a paucity of randomized trial evidence for its use. Here, we will review the latest evidence for its usage in different clinical settings. Recent findings There have been decades of nonrandomized and observational data available, but only in the last 3 years has there been availability of randomized evidence for IABP use in acute myocardial infarction (AMI) with cardiogenic shock, ST elevation acute coronary syndromes (STE-ACS) without shock and high-risk percutaneous coronary intervention (PCI) cohorts. Summary To the surprise of many, despite the sound physiological benefits achieved by the use of IABP counterpulsation in these situations, all the recent trials did not achieve the primary endpoint, although there is a trend towards long-term benefit with its use. This may alter its elective use in practice and may lead to changes in current guidance and possibly increase the focus on other mechanical circulatory devices. Despite the neutral primary endpoints in these recent trials, there is a signal that a subset of the population may benefit by elective IABP use and get good haemodynamic support, thus suggesting, in our view, that further understanding and research are required to gain maximum physiological benefit from this device and to aid decision making for an individualized, patient-centred approach.

Long-Term Mortality Data from the Balloon-Pump Assisted Coronary Intervention Study (BCIS-1): A Randomized Controlled Trial of Elective Balloon Counterpulsation during High-Risk PCI

Background— There is conflicting evidence on the utility of elective intra-aortic balloon pump (IABP) use during high-risk percutaneous coronary intervention (PCI). Observational series have indicated a reduction in major in-hospital adverse events, although randomized trial evidence does not support this. A recent study has suggested a mortality benefit trend early after PCI, but there are currently no long-term outcome data from randomized trials in this setting. Methods and Results— Three hundred one patients with left ventricular impairment (ejection fraction <30%) and severe coronary disease (BCIS-1 jeopardy score ≥8; maximum possible score=12) were randomized to receive PCI with elective IABP support (n=151) or without planned IABP support (n=150). Long-term all-cause mortality was assessed by tracking the databases held at the Office of National Statistics (in England and Wales) and the General Register Office (in Scotland). The groups were balanced in terms of baseline characteristics (left ventricular ejection fraction, 23.6%; BCIS-1 jeopardy score, 10.4) and the amount and type of revascularization performed. Mortality data were available for the entire cohort at a median of 51 months (interquartile range, 41–58) from randomization. All-cause mortality at follow-up was 33% in the overall cohort, with significantly fewer deaths occurring in the elective IABP group (n=42) than in the group that underwent PCI without planned IABP support (n=58) (hazard ratio, 0.66; 95% confidence interval, 0.44–0.98; P=0.039). Conclusions— In patients with severe ischemic cardiomyopathy treated with PCI, all-cause mortality was 33% at a median of 51 months. Elective IABP use during PCI was associated with a 34% relative reduction in all-cause mortality compared with unsupported PCI. Clinical Trial Registration— URL: http://www.isrctn.org. Unique identifier: ISRCTN40553718; and http://www.clinicaltrials.gov. Unique identifier: NCT00910481.

DOPPLER INDICES OF RESISTANCE ARE SUPERIOR TO THERMODILUTION INDICES AT PREDICTING CORONARY MICROVASCULAR DYSFUNCTION

methods: 27-patients (64±11 yrs) were recruited, 48% following an acute coronary syndrome. Simultaneous pressure, Doppler flow velocity and cold-bolus transit time were measured in 40 unobstructed coronary arteries, using a Volcano Combowire and St Jude Pressure Wire, at rest and during intravenous adenosine hyperemia. The following were calculated using standard definitions: coronary flow reserve (CFR) by thermodilution and Doppler, hMR and IMR. 3T cardiac MRI scans were carried out and Myocardial Perfusion Reserve Index (MPRI) calculated in the corresponding segments as previously described.