Intra-aortic balloon pump (IABP) therapy is a widely used intervention for acute myocardial infar... more Intra-aortic balloon pump (IABP) therapy is a widely used intervention for acute myocardial infarction with cardiogenic shock. Guidelines, which previously strongly recommended it, have recently undergone substantial change. To assess IABP efficacy in acute myocardial infarction. Human studies found in Pubmed, Embase, and Cochrane libraries through December 2014 and in reference lists of selected articles. Search strings were "myocardial infarction" or "acute coronary syndrome" and "intra-aortic balloon pump" or "counterpulsation." Randomized clinical trials (RCTs) and observational studies comparing use of IABP with no IABP in patients with acute myocardial infarction. Two reviewers independently extracted the data, and risk of bias in RCTs was assessed using the Cochrane risk of bias tool. We conducted separate meta-analyses of the RCTs and observational studies. Data were quantitatively synthesized using random-effects meta-analysis. Thirty-day mortality. There were 12 eligible RCTs randomizing 2123 patients. In the RCTs, IABP use had no statistically significant effect on mortality (odds ratio [OR], 0.96 [95% CI, 0.74-1.24]), with no significant heterogeneity among trials (I2 = 0%; P = .52). This result was consistent when studies were stratified by the presence (OR, 0.94 [95% CI, 0.69-1.28]; P = .69, I2 = 0%) or absence (OR, 0.98 [95% CI, 0.57-1.69]; P = .95, I2 = 17%) of cardiogenic shock. There were 15 eligible observational studies totaling 15 530 patients. Their results were mutually conflicting (heterogeneity I2 = 97%; P < .001), causing wide uncertainty in the summary estimate for the association with mortality (OR, 0.96 [95% CI, 0.54-1.70]). A simple index of baseline risk marker imbalance in the observational studies appeared to explain much of the heterogeneity in the observational data (R2meta = 46.2%; P < .001). Use of IABP was not found to improve mortality among patients with acute myocardial infarction in the RCTs, regardless of whether patients had cardiogenic shock. The observational studies showed a variety of mutually contradictory associations between IABP therapy and mortality, much of which was explained by the differences between studies in the balance of risk factors between IABP and non-IABP groups.
Journal of the American College of Cardiology, Jan 2, 2014
Over the past 2 decades, there have been numerous stem cell studies focused on cardiac diseases, ... more Over the past 2 decades, there have been numerous stem cell studies focused on cardiac diseases, ranging from proof-of-concept to phase 2 trials. This series of papers focuses on the legacy of these studies and the outlook for future treatment of cardiac diseases with stem cell therapies. The first section by Drs. Rosen and Myerburg is an independent review that analyzes the basic science and translational strategies supporting the rapid advance of stem cell technology to the clinic, the philosophies behind them, trial designs, and means for going forward that may impact favorably on progress. The second and third sections were collected as responses to the initial section of this review. The commentary by Drs. Francis and Cole discusses the review by Drs. Rosen and Myerburg and details how trial outcomes can be affected by noise, poor trial design (particularly the absence of blinding), and normal human tendencies toward optimism and denial. The final, independent paper by Dr. Marb...
European Heart Journal - Cardiovascular Imaging, 2014
Echocardiographic velocity measurements can be more consistent than previously suspected. The sta... more Echocardiographic velocity measurements can be more consistent than previously suspected. The statistically modal velocity, found at the centre of the spectral pulsed wave tissue Doppler envelope, most closely represents true tissue velocity. This article includes downloadable, vendor-independent software enabling calibration of echocardiographic machines using a simple, inexpensive in vitro setup.
We examined the prognostic utility of rate of change in serum albumin over time in chronic heart ... more We examined the prognostic utility of rate of change in serum albumin over time in chronic heart failure (CHF), as well as the utility of multivariate dynamic risk modelling. The survival implication of ∆albumin was analysed in 232 systolic CHF patients and validated in 212 patients. A multivariate dynamic risk score predicated on the rate of change in 6 simple indices including albumin was calculated and related to mortality. In derivation patients, 50 (22%) deaths occurred over 13 months. Greater rates of decline in albumin related to higher mortality (HR 0.55, 95% CI 0.41-0.73, P<0.0001) independently, incrementally and more accurately than other covariates including baseline albumin. A rate of attenuation >0.4 g/dL/month optimally forecasted death and was associated with a 5-fold escalated risk of mortality (HR 5.13, 95% CI 2.92-9.00, P<0.0001). Similar results were seen in the validation cohort. On multivariate dynamic risk modelling, survival at 1-year worsened with higher scores-a score ≥ 3 was associated with a 12-fold greater risk of death than a score of 0, a 6-fold higher risk of death than a score of 1, and a 4-fold enhanced risk of mortality than a score of 2. Attenuations in serum albumin over time relate to increased mortality in CHF, and a risk model predicated on the rate of change in 6 simple indices can identify patients at a 12-fold enhanced risk of death over the coming year.
Background: Cardiologists frequently advise on perioperative care for non-cardiac surgery and req... more Background: Cardiologists frequently advise on perioperative care for non-cardiac surgery and require guidance based on randomised controlled trials that are not discredited by misconduct or misreporting. Regional political bodies currently do not provide this. We therefore examined the credible randomised controlled trial (RCT) evidence on key cardiac perioperative questions which currently have 14 recommendations. Methods: Three aspects of perioperative measures were considered: perioperative statins, preoperative stresstesting and perioperative beta-blockade. One author searched PubMed for RCTs considering these topics. All authors independently assessed the RCTs and then collaboratively composed guidelines. Results: Perioperative statin therapy has been examined by three RCTs, DECREASE III and IV, which are discredited and a third containing serious inconsistencies undermining its validity. Preoperative stress testing has been examined by two RCTs: one discredited trial, DECREASE II, and a second which found no benefit. Perioperative beta-blockade has been examined by eleven RCTs, two of which are discredited. The nine remaining trials together suggest that perioperative beta-blockade increases mortality. Conclusions: When the non-credible RCTs are omitted, the evidence base on these three subjects is much smaller than previously believed: 14 recommendations can be replaced by 3. Current guideline arrangements collectively paralyse the numerous signatories from making urgent amendments after initial publication, even when important new information comes to light. Clinicians simply have to wait for the routine five-year expiry. We present a concise scientifically based guideline and commit to updating it responsibly.
Background: Transmitral pulse wave (PW) Doppler and annular tissue Doppler velocity measurements ... more Background: Transmitral pulse wave (PW) Doppler and annular tissue Doppler velocity measurements provide valuable diagnostic and prognostic information. However, they depend on an echocardiographer manually selecting positions to make the measurements. This is time-consuming and open to variability, especially by less experienced operators. We present a new, automated method to select consistent Doppler velocity sites to measure blood flow and muscle function. Methods: Our automated algorithm combines speckle tracking and colour flow mapping to locate the septal and lateral mitral valve annuli (to measure peak early diastolic velocity, E′) and the mitral valve inflow (to measure peak inflow velocity, E). We also automate peak velocity measurements from resulting PW Doppler traces. The algorithm-selected locations and time taken to identify them were compared against a panel of echo specialiststhe current "gold standard". Results: The algorithm identified positions to measure Doppler velocities within 3.6 ± 2.2 mm (mitral inflow), 3.2 ± 1.8 mm (septal annulus) and 3.8 ± 1.5 mm (lateral annulus) of the consensus of 3 specialists. This was less than the average 4 mm fidelity with which the specialists could themselves identify the points. The automated algorithm could potentially reduce the time taken to make these measurements by 60 ± 15%. Conclusions: Our automated algorithm identified sampling positions for measurement of mitral flow, septal and lateral tissue velocities as reliably as specialists. It provides a rapid, easy method for new specialists and potentially non-specialists to make automated measurements of key cardiac physiological indices. This could help support decision-making, without introducing delay and extend availability of echocardiography to more patients.
Background: Heart failure (HF) imposes both direct costs to healthcare systems and indirect costs... more Background: Heart failure (HF) imposes both direct costs to healthcare systems and indirect costs to society through morbidity, unpaid care costs, premature mortality and lost productivity. The global economic burden of HF is not known. Methods: We estimated the overall cost of heart failure in 2012, in both direct and indirect terms, across the globe. Existing country-specific heart failure costs analyses were expressed as a proportion of gross domestic product and total healthcare spend. Using World Bank data, these proportional values were used to interpolate the economic cost of HF for countries of the world where no published data exists. Countries were categorized according to their level of economic development to investigate global patterns of spending. Results: 197 countries were included in the analysis, covering 98.7% of the world's population. The overall economic cost of HF in 2012 was estimated at $108 billion per annum. Direct costs accounted for~60% ($65 billion) and indirect costs accounted for~40% ($43 billion) of the overall spend. Heart failure spending varied widely between high-income and middle and low-income countries. High-income countries spend a greater proportion on direct costs: a pattern reversed for middle and low-income countries. Conclusions: Heart failure imposes a huge economic burden, estimated at $108 billion per annum. With an aging, rapidly expanding and industrializing global population this value will continue to rise.
... Correspondence to Dr Iqbal S Malik, Mary Stanford Wing, St Mary's Campus, Imperial C... more ... Correspondence to Dr Iqbal S Malik, Mary Stanford Wing, St Mary's Campus, Imperial College Healthcare NHS Trust, Praed Street, London W2 1NY, UK; Iqbal.malik{at}imperial. nhs.uk. Contributors All authors contributed equally to the editorial. ...
Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology, 2014
Intra-aortic balloon pump (IABP) therapy is a widely used intervention for acute myocardial infar... more Intra-aortic balloon pump (IABP) therapy is a widely used intervention for acute myocardial infarction with cardiogenic shock. Guidelines, which previously strongly recommended it, have recently undergone substantial change. To assess IABP efficacy in acute myocardial infarction. Human studies found in Pubmed, Embase, and Cochrane libraries through December 2014 and in reference lists of selected articles. Search strings were "myocardial infarction" or "acute coronary syndrome" and "intra-aortic balloon pump" or "counterpulsation." Randomized clinical trials (RCTs) and observational studies comparing use of IABP with no IABP in patients with acute myocardial infarction. Two reviewers independently extracted the data, and risk of bias in RCTs was assessed using the Cochrane risk of bias tool. We conducted separate meta-analyses of the RCTs and observational studies. Data were quantitatively synthesized using random-effects meta-analysis. Thirty-day mortality. There were 12 eligible RCTs randomizing 2123 patients. In the RCTs, IABP use had no statistically significant effect on mortality (odds ratio [OR], 0.96 [95% CI, 0.74-1.24]), with no significant heterogeneity among trials (I2 = 0%; P = .52). This result was consistent when studies were stratified by the presence (OR, 0.94 [95% CI, 0.69-1.28]; P = .69, I2 = 0%) or absence (OR, 0.98 [95% CI, 0.57-1.69]; P = .95, I2 = 17%) of cardiogenic shock. There were 15 eligible observational studies totaling 15 530 patients. Their results were mutually conflicting (heterogeneity I2 = 97%; P < .001), causing wide uncertainty in the summary estimate for the association with mortality (OR, 0.96 [95% CI, 0.54-1.70]). A simple index of baseline risk marker imbalance in the observational studies appeared to explain much of the heterogeneity in the observational data (R2meta = 46.2%; P < .001). Use of IABP was not found to improve mortality among patients with acute myocardial infarction in the RCTs, regardless of whether patients had cardiogenic shock. The observational studies showed a variety of mutually contradictory associations between IABP therapy and mortality, much of which was explained by the differences between studies in the balance of risk factors between IABP and non-IABP groups.
Journal of the American College of Cardiology, Jan 2, 2014
Over the past 2 decades, there have been numerous stem cell studies focused on cardiac diseases, ... more Over the past 2 decades, there have been numerous stem cell studies focused on cardiac diseases, ranging from proof-of-concept to phase 2 trials. This series of papers focuses on the legacy of these studies and the outlook for future treatment of cardiac diseases with stem cell therapies. The first section by Drs. Rosen and Myerburg is an independent review that analyzes the basic science and translational strategies supporting the rapid advance of stem cell technology to the clinic, the philosophies behind them, trial designs, and means for going forward that may impact favorably on progress. The second and third sections were collected as responses to the initial section of this review. The commentary by Drs. Francis and Cole discusses the review by Drs. Rosen and Myerburg and details how trial outcomes can be affected by noise, poor trial design (particularly the absence of blinding), and normal human tendencies toward optimism and denial. The final, independent paper by Dr. Marb...
European Heart Journal - Cardiovascular Imaging, 2014
Echocardiographic velocity measurements can be more consistent than previously suspected. The sta... more Echocardiographic velocity measurements can be more consistent than previously suspected. The statistically modal velocity, found at the centre of the spectral pulsed wave tissue Doppler envelope, most closely represents true tissue velocity. This article includes downloadable, vendor-independent software enabling calibration of echocardiographic machines using a simple, inexpensive in vitro setup.
We examined the prognostic utility of rate of change in serum albumin over time in chronic heart ... more We examined the prognostic utility of rate of change in serum albumin over time in chronic heart failure (CHF), as well as the utility of multivariate dynamic risk modelling. The survival implication of ∆albumin was analysed in 232 systolic CHF patients and validated in 212 patients. A multivariate dynamic risk score predicated on the rate of change in 6 simple indices including albumin was calculated and related to mortality. In derivation patients, 50 (22%) deaths occurred over 13 months. Greater rates of decline in albumin related to higher mortality (HR 0.55, 95% CI 0.41-0.73, P<0.0001) independently, incrementally and more accurately than other covariates including baseline albumin. A rate of attenuation >0.4 g/dL/month optimally forecasted death and was associated with a 5-fold escalated risk of mortality (HR 5.13, 95% CI 2.92-9.00, P<0.0001). Similar results were seen in the validation cohort. On multivariate dynamic risk modelling, survival at 1-year worsened with higher scores-a score ≥ 3 was associated with a 12-fold greater risk of death than a score of 0, a 6-fold higher risk of death than a score of 1, and a 4-fold enhanced risk of mortality than a score of 2. Attenuations in serum albumin over time relate to increased mortality in CHF, and a risk model predicated on the rate of change in 6 simple indices can identify patients at a 12-fold enhanced risk of death over the coming year.
Background: Cardiologists frequently advise on perioperative care for non-cardiac surgery and req... more Background: Cardiologists frequently advise on perioperative care for non-cardiac surgery and require guidance based on randomised controlled trials that are not discredited by misconduct or misreporting. Regional political bodies currently do not provide this. We therefore examined the credible randomised controlled trial (RCT) evidence on key cardiac perioperative questions which currently have 14 recommendations. Methods: Three aspects of perioperative measures were considered: perioperative statins, preoperative stresstesting and perioperative beta-blockade. One author searched PubMed for RCTs considering these topics. All authors independently assessed the RCTs and then collaboratively composed guidelines. Results: Perioperative statin therapy has been examined by three RCTs, DECREASE III and IV, which are discredited and a third containing serious inconsistencies undermining its validity. Preoperative stress testing has been examined by two RCTs: one discredited trial, DECREASE II, and a second which found no benefit. Perioperative beta-blockade has been examined by eleven RCTs, two of which are discredited. The nine remaining trials together suggest that perioperative beta-blockade increases mortality. Conclusions: When the non-credible RCTs are omitted, the evidence base on these three subjects is much smaller than previously believed: 14 recommendations can be replaced by 3. Current guideline arrangements collectively paralyse the numerous signatories from making urgent amendments after initial publication, even when important new information comes to light. Clinicians simply have to wait for the routine five-year expiry. We present a concise scientifically based guideline and commit to updating it responsibly.
Background: Transmitral pulse wave (PW) Doppler and annular tissue Doppler velocity measurements ... more Background: Transmitral pulse wave (PW) Doppler and annular tissue Doppler velocity measurements provide valuable diagnostic and prognostic information. However, they depend on an echocardiographer manually selecting positions to make the measurements. This is time-consuming and open to variability, especially by less experienced operators. We present a new, automated method to select consistent Doppler velocity sites to measure blood flow and muscle function. Methods: Our automated algorithm combines speckle tracking and colour flow mapping to locate the septal and lateral mitral valve annuli (to measure peak early diastolic velocity, E′) and the mitral valve inflow (to measure peak inflow velocity, E). We also automate peak velocity measurements from resulting PW Doppler traces. The algorithm-selected locations and time taken to identify them were compared against a panel of echo specialiststhe current "gold standard". Results: The algorithm identified positions to measure Doppler velocities within 3.6 ± 2.2 mm (mitral inflow), 3.2 ± 1.8 mm (septal annulus) and 3.8 ± 1.5 mm (lateral annulus) of the consensus of 3 specialists. This was less than the average 4 mm fidelity with which the specialists could themselves identify the points. The automated algorithm could potentially reduce the time taken to make these measurements by 60 ± 15%. Conclusions: Our automated algorithm identified sampling positions for measurement of mitral flow, septal and lateral tissue velocities as reliably as specialists. It provides a rapid, easy method for new specialists and potentially non-specialists to make automated measurements of key cardiac physiological indices. This could help support decision-making, without introducing delay and extend availability of echocardiography to more patients.
Background: Heart failure (HF) imposes both direct costs to healthcare systems and indirect costs... more Background: Heart failure (HF) imposes both direct costs to healthcare systems and indirect costs to society through morbidity, unpaid care costs, premature mortality and lost productivity. The global economic burden of HF is not known. Methods: We estimated the overall cost of heart failure in 2012, in both direct and indirect terms, across the globe. Existing country-specific heart failure costs analyses were expressed as a proportion of gross domestic product and total healthcare spend. Using World Bank data, these proportional values were used to interpolate the economic cost of HF for countries of the world where no published data exists. Countries were categorized according to their level of economic development to investigate global patterns of spending. Results: 197 countries were included in the analysis, covering 98.7% of the world's population. The overall economic cost of HF in 2012 was estimated at $108 billion per annum. Direct costs accounted for~60% ($65 billion) and indirect costs accounted for~40% ($43 billion) of the overall spend. Heart failure spending varied widely between high-income and middle and low-income countries. High-income countries spend a greater proportion on direct costs: a pattern reversed for middle and low-income countries. Conclusions: Heart failure imposes a huge economic burden, estimated at $108 billion per annum. With an aging, rapidly expanding and industrializing global population this value will continue to rise.
... Correspondence to Dr Iqbal S Malik, Mary Stanford Wing, St Mary's Campus, Imperial C... more ... Correspondence to Dr Iqbal S Malik, Mary Stanford Wing, St Mary's Campus, Imperial College Healthcare NHS Trust, Praed Street, London W2 1NY, UK; Iqbal.malik{at}imperial. nhs.uk. Contributors All authors contributed equally to the editorial. ...
Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology, 2014
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