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Importance of (measuring) the end-systolic volume index in predicting survival

2018-01-03T06:35:31-08:00

To the Editor Prior et al.1 report on survival prediction in patients with ischaemic cardiomyopathy following surgical intervention and found that end-systolic volume (ESV) index (I) is the strongest indicator of survival. Their findings are partly based on an imputation procedure which is reported to have not affected the outcomes. We have no reason to doubt this statement, but we are left with three major issues:

  • Some inconsistencies require clarification. In figure 1, the ESVI range is limited to 150, while table 3 and figure 2 document a maximum of 281 mL/m2.

  • We fully acknowledge that a variety of mathematical models can be employed for imputation as long as a well-defined range is considered. To relate ESVI to ejection fraction (EF), the authors opted for a polynomial including EF, the square of EF and three more variables including age. Cross-terms are not mentioned. This mathematical approach results in...




  • The authors reply to the letter from Kerkhof et al entitled 'The importance of (measuring) the end-systolic volume index in predicting survival

    2018-01-03T06:35:31-08:00

    We thank Kerkhof et al1 for their interest in our paper2 and are pleased they agree with our conclusion that accurate determination of end-systolic volume index (ESVI) is important in patients with reduced LVEF.

  • Table 3 and figure 2 show the entire range of ESVI values. The scatter plot of the individual data points (figure 2) and summary statistics presented in table 3 reveal the data are highly skewed to the right such that most values fall at the lower end of the range. Given that 90% of the observed ESVI values are between 40 mL/m2 and 150 mL/m2, we showed this range in figure 4.

  • Data are sparse in the upper range of ESVI values. Imputed ESVI values for the 76 patients fall in a range where 84% of measured values are located. In the sentence, ‘Linear, quadratic, and cubic terms, linear splines, and a...




  • Heartbeat: Age-related changes in the cardiac response to exercise

    2018-01-03T06:35:31-08:00

    Age-related decline in physical performance is inevitable. The heart is not an exception. Nathania and colleagues1 investigated the relationship between cardiac high-energy phosphate metabolism and cardiac performance using 31P cardiac magnetic resonance spectroscopy and cardiopulmonary exercise testing in young (≤50 years, n=20) and old (≥60 years, n=15) healthy women. They found a positive and significant relationship between cardiac high-energy phosphate metabolism and cardiac performance. In addition, metabolism and peak cardiac power declined with age. They also found that phosphocreatine (PCr)-to-ATP ratio showed a significant positive relationship with early-to-late diastolic filling ratio (r=0.46, P=0.02) and peak oxygen consumption (r=0.51, P=0.01) (figure 1). Although the relationships were only modest and cardiac metabolism was mostly related to contractile function, decreased cardiac metabolism may play a role in the progression of heart failure with preserved ejection fraction (HFpEF) which is the most frequent cause of heart failure in the...




    Age-related reduction of myocardial metabolic efficiency: Is it time to routinely measure myocardial metabolism to monitor cardiac health?

    2018-01-03T06:35:31-08:00

    Cardiovascular ageing represents a major burden for elderly patients and healthcare providers. The current impressive increase of life expectation highlights the need to understand the (patho)physiology of ageing in order to define potential therapeutic strategies to confront this challenge. Among many unresolved issues, the age-related progressive reduction of myocardial efficiency certainly represents one of the most fascinating.

    Age-related reduction of cardiac cellular metabolic reserve

    In normal myocardium, the concentrations of the high-energy phosphate compounds ATP and phosphocreatine (PCr) are tightly controlled over a range of performance because ATP production by mitochondrial oxidative phosphorylation is closely coupled to ATP utilisation by cytosolic adenosine triphosphatases. ATP is the direct energy source for energy-consuming reactions in the cell, while PCr acts as an energy storage compound and, in addition, as an energy transport molecule in the ‘creatine kinase-PCr energy shuttle’. Previous clinical studies using phosphorus-31 magnetic resonance spectroscopy (31P-MRS) to measure PCr/ATP ratios...




    Reference invasive tests of microvascular injury in myocardial infarction

    2018-01-03T06:35:31-08:00

    In patients with ST-segment elevation myocardial infarction (STEMI), primary percutaneous coronary intervention (PCI) successfully restores normal antegrade flow in the infarct-related artery in nearly 99% of patients. However, approximately half of all STEMI patients have failed microcirculatory reperfusion, as reflected by microvascular obstruction (MVO), and one-third have myocardial haemorrhage, reflecting severe, ‘downstream’, potentially irreversible, microvascular injury.1

    MVO is the ‘Achilles Heel’ of primary PCI, yet clinicians are generally unaware of the occurrence of MVO and myocardial haemorrhage in their patients, unless cardiac magnetic resonance (CMR) is performed. However, CMR is not done routinely. Other established investigations for detecting failure of myocardial reperfusion, such as angiographic, or electrocardiographic parameters, lack sensitivity and reproducibility in clinical practice.

    Immediate invasive measurement of microvascular resistance at the time of PCI has the potential to optimise the approach to therapeutic interventions by: (1) acutely identifying patients at high risk of MVO who are most...




    Cochrane corner: long-term hormone therapy for perimenopausal and postmenopausal women

    2018-01-03T06:35:31-08:00

    Background

    Hormone therapy (HT) has been used for over 50 years for treating menopausal vasomotor symptoms, and its efficacy is well established.

    HT consists of oestrogen either alone or combined with a progestogen. Progestogen use reduces the risk of endometrial hyperplasia associated with unopposed oestrogen in women with a uterus. Clinical effects vary according to the type of HT and duration of use.

    Until about 15 years ago, commonly held expert opinion (supported by strong observational evidence) was that most postmenopausal women could benefit from HT. It was widely used for the management or prevention of chronic conditions such as coronary heart disease (CHD) and osteoporotic fractures, and it was suggested that HT might also help to prevent cognitive decline and dementia. As CHD is the most common cause of death and morbidity in older women, a significant reduction in CHD risk would potentially outweigh any adverse effects of...




    Acute stress-induced (takotsubo) cardiomyopathy

    2018-01-03T06:35:31-08:00

    Acute stress-induced (takotsubo) cardiomyopathy has a dramatic clinical presentation, mimicking an acute myocardial infarction and is triggered by intense emotional or physical stress. In this paper, we review the current state of knowledge of the mechanistic physiology underlying the left ventricular ballooning. The pathophysiology of the recovery from this acute heart failure syndrome is presented. The short-term and long-term outlook puts this new syndrome on a different perspective compared with recently held views. Current knowledge on susceptibility and predisposition already define distinctive characteristics of patients with takotsubo compared with myocardial infarction. Gaps in knowledge and future directions of research are identified in order to best direct efforts for identifying specific therapies for this condition, in the acute setting, to mitigate postacute symptoms or to prevent recurrences, none of which exist.




    Evaluation of aortic regurgitation with cardiac magnetic resonance imaging: a systematic review

    2018-01-03T06:35:31-08:00

    This review summaries the utility, application and data supporting use of cardiac magnetic resonance imaging (CMR) to evaluate and quantitate aortic regurgitation. We systematically searched Medline and PubMed for original research articles published since 2000 that provided data on the quantitation of aortic regurgitation by CMR and identified 11 articles for review. Direct aortic measurements using phase contrast allow quantitation of volumetric flow across the aortic valve and are highly reproducible and accurate compared with echocardiography. However, this technique requires diligence in prescribing the correct imaging planes in the aorta. Volumetric analytic techniques using differences in ventricular volumes are also highly accurate but less than phase contrast techniques and only accurate when concomitant valvular disease is absent. Comparison of both aortic and ventricular data for internal data verification ensures fidelity of aortic regurgitant data. CMR data can be applied to many types of aortic valve regurgitation including combined aortic stenosis with regurgitation, congenital valve diseases and post-transcatheter valve placement. CMR also predicts those patients who progress to surgery with high overall sensitivity and specificity. Future studies of CMR in patients with aortic regurgitation to quantify the incremental benefit over echocardiography as well as prediction of cardiovascular events are warranted.




    Impact of age on the association between cardiac high-energy phosphate metabolism and cardiac power in women

    2018-01-03T06:35:31-08:00

    Objective

    Diminished cardiac high-energy phosphate metabolism (phosphocreatine-to-ATP (PCr:ATP) ratio) and cardiac power with age may play an important roles in development of cardiac dysfunction and heart failure. The study defines the impact of age on PCr:ATP ratio and cardiac power and their relationship.

    Methods

    Thirty-five healthy women (young≤50 years, n=20; and old≥60 years, n=15) underwent cardiac MRI with 31P spectroscopy to assess PCr:ATP ratio and performed maximal graded cardiopulmonary exercise testing with simultaneous gas-exchange and central haemodynamic measurements. Peak cardiac power output, as the best measure of pumping capability and performance of the heart, was calculated as the product of peak exercise cardiac output and mean arterial blood pressure.

    Results

    PCr:ATP ratio was significantly lower in old compared with young age group (1.92±0.48 vs 2.29±0.55, p=0.03), as were peak cardiac power output (3.35±0.73 vs 4.14±0.81W, p=0.01), diastolic function (ie, early-to-late diastolic filling ratio, 1.33±0.54 vs 3.07±1.84, p<0.01) and peak exercise oxygen consumption (1382.9±255.0 vs 1940.3±434.4 mL/min, p<0.01). Further analysis revealed that PCr:ATP ratio shows a significant positive relationship with early-to-late diastolic filling ratio (r=0.46, p=0.02), peak cardiac power output (r=0.44, p=0.02) and peak oxygen consumption (r=0.51, p=0.01).

    Conclusions

    High-energy phosphate metabolism and peak power of the heart decline with age. Significant positive relationship between PCr:ATP ratio, early-to-late diastolic filling ratio and peak cardiac power output suggests that cardiac high-energy phosphate metabolism may be an important determinant of cardiac function and performance.




    Association between chronic immune-mediated inflammatory diseases and cardiovascular risk

    2018-01-03T06:35:31-08:00

    Objective

    To examine the association between chronic immune-mediated diseases (rheumatoid arthritis, systemic lupus erythematosus or the following chronic immune-mediated inflammatory diagnoses groups: inflammatory bowel diseases, inflammatory polyarthropathies, systemic connective tissue disorders and spondylopathies) and the 6-year coronary artery disease, stroke, cardiovascular disease incidence and overall mortality; and to estimate the population attributable fractions for all four end-points for each chronic immune-mediated inflammatory disease.

    Methods

    Cohort study of individuals aged 35–85 years, with no history of cardiovascular disease from Catalonia (Spain). The coded diagnoses of chronic immune-mediated diseases and cardiovascular diseases were ascertained and registered using validated codes, and date of death was obtained from administrative data. Cox regression models for each outcome according to exposure were fitted to estimate HRs in two models 1 : after adjustment for sex, age, cardiovascular risk factors and 2 further adjusted for drug use. Population attributable fractions were estimated for each exposure.

    Results

    Data were collected from 991 546 participants. The risk of cardiovascular disease was increased in systemic connective tissue disorders (model 1: HR=1.38 (95% CI 1.21 to 1.57) and model 2: HR=1.31 (95% CI 1.15 to 1.49)), rheumatoid arthritis (HR=1.43 (95% CI 1.26 to 1.62) and HR=1.31 (95% CI 1.15 to 1.49)) and inflammatory bowel diseases (HR=1.18 (95% CI 1.06 to 1.32) and HR=1.12 (95% CI 1.01 to 1.25)). The effect of anti-inflammatory treatment was significant in all instances (HR=1.50 (95% CI 1.24 to 1.81); HR=1.47 (95% CI 1.23 to 1.75); HR=1.43 (95% CI 1.19 to 1.73), respectively). The population attributable fractions for all three disorders were 13.4%, 15.7% and 10.7%, respectively.

    Conclusion

    Systemic connective tissue disorders and rheumatoid arthritis conferred the highest cardiovascular risk and population impact, followed by inflammatory bowel diseases.




    Hyperaemic microvascular resistance predicts clinical outcome and microvascular injury after myocardial infarction

    2018-01-03T06:35:31-08:00

    Objectives

    Early detection of microvascular dysfunction after acute myocardial infarction (AMI) could identify patients at high risk of adverse clinical outcome, who may benefit from adjunctive treatment. Our objective was to compare invasively measured coronary flow reserve (CFR) and hyperaemic microvascular resistance (HMR) for their predictive power of long-term clinical outcome and cardiac magnetic resonance (CMR)-defined microvascular injury (MVI).

    Methods

    Simultaneous intracoronary Doppler flow velocity and pressure measurements acquired immediately after revascularisation for AMI from five centres were pooled. Clinical follow-up was completed for 176 patients (mean age 60±10 years; 140(80%) male; ST-elevation myocardial infarction (STEMI) 130(74%) and non-ST-segment elevation myocardial infarction 46(26%)) with median follow-up time of 3.2 years. In 110 patients with STEMI, additional CMR was performed.

    Results

    The composite end point of death and hospitalisation for heart failure occurred in 17 patients (10%). Optimal cut-off values to predict the composite end point were 1.5 for CFR and 3.0 mm Hg cm–1•s for HMR. CFR <1.5 was predictive for the composite end point (HR 3.5;95% CI 1.1 to 10.8), but not for its individual components. HMR ≥3.0 mm Hg cm–1 s was predictive for the composite end point (HR 7.0;95% CI 1.5 to 33.7) as well as both individual components. HMR had significantly greater area under the receiver operating characteristic curve for MVI than CFR. HMR remained an independent predictor of adverse clinical outcome and MVI, whereas CFR did not.

    Conclusions

    HMR measured immediately following percutaneous coronary intervention for AMI with a cut-off value of 3.0 mm Hg cm–1 s, identifies patients with MVI who are at high risk of adverse clinical outcome. For this purpose, HMR is superior to CFR.




    Association of cardiovascular disease risk factors with coronary artery calcium volume versus density

    2018-01-03T06:35:31-08:00

    Objectives

    Recently, the density score of coronary artery calcium (CAC) has been shown to be associated with a lower risk of cardiovascular disease (CVD) events at any level of CAC volume. Whether risk factors for CAC volume and CAC density are similar or distinct is unknown. We sought to evaluate the associations of CVD risk factors with CAC volume and CAC density scores.

    Methods

    Baseline measurements from 6814 participants free of clinical CVD were collected for the Multi-Ethnic Study of Atherosclerosis. Participants with detectable CAC (n=3398) were evaluated for this study. Multivariable linear regression models were used to evaluate independent associations of CVD risk factors with CAC volume and CAC density scores.

    Results

    Whereas most CVD risk factors were associated with higher CAC volume scores, many risk factors were associated with lower CAC density scores. For example, diabetes was associated with a higher natural logarithm (ln) transformed CAC volume score (standardised β=0.44 (95% CI 0.31 to 0.58) ln-units) but a lower CAC density score (β=–0.07 (–0.12 to –0.02) density units). Chinese, African-American and Hispanic race/ethnicity were each associated with lower ln CAC volume scores (β=–0.62 (–0.83to –0.41), –0.52 (–0.64 to –0.39) and –0.40 (–0.55 to –0.26) ln-units, respectively) and higher CAC density scores (β= 0.41 (0.34 to 0.47), 0.18 (0.12 to 0.23) and 0.21 (0.15 to 0.26) density units, respectively) relative to non-Hispanic White.

    Conclusions

    In a cohort free of clinical CVD, CVD risk factors are differentially associated with CAC volume and density scores, with many CVD risk factors inversely associated with the CAC density score after controlling for the CAC volume score. These findings suggest complex associations between CVD risk factors and these components of CAC.




    Non-ischaemic cardiomyopathy, sudden death and implantable defibrillators: a review and meta-analysis

    2018-01-03T06:35:31-08:00

    Objective

    The recent Danish Study to Assess the Efficacy of ICDs in Patients with Non-ischemic Systolic Heart Failure on Mortality (DANISH) trial suggested that implantable cardioverter defibrillators (ICDs) do not reduce overall mortality in patients with non-ischaemic cardiomyopathy (NICM), despite reducing sudden cardiac death. We performed an updated meta-analysis to examine the impact of ICD therapy on mortality in NICM patients.

    Methods

    A systematic search for studies that examined the effect of ICDs on outcomes in NICM was performed. Our analysis compared patients randomised to an ICD with those randomised to no ICD, and examined the endpoint of overall mortality.

    Results

    Six primary prevention trials and two secondary prevention trials were identified that met the pre-specified search criteria. Using a fixed-effects model, analysis of primary prevention trials revealed a reduction in overall mortality with ICD therapy (RR 0.76, 95% CI 0.65 to 0.91).

    Conclusions

    Although our updated meta-analysis demonstrates a survival benefit of ICD therapy, the effect is substantively weakened by the inclusion of the DANISH trial—which is both the largest and most recent of the analysed trials—indicating that the residual pooled benefit of ICDs may reflect the risk of sudden death in older trials which included patients treated sub-optimally by contemporary standards. As such, these data must be interpreted cautiously. The results of the DANISH trial emphasise that there is no ‘one size fits all’ indication for primary prevention ICDs in NICM patients, and clinicians must consider age and comorbidity on an individual basis when determining whether a defibrillator is appropriate.




    Predictors of 1-year mortality in heart transplant recipients: a systematic review and meta-analysis

    2018-01-03T06:35:31-08:00

    Objective

    A systematic summary of the observational studies informing heart transplant guideline recommendations for selection of candidates and donors has thus far been unavailable. We performed a meta-analysis to better understand the impact of such known risk factors.

    Methods

    We systematically searched and meta-analysed the association between known pretransplant factor and 1-year mortality identified by multivariable regression models. Our review used the Grading of Recommendations, Assessment, Development and Evaluation for assessing the quality of assessment. We pooled risk estimates by using random effects models.

    Results

    Recipient variables including age (HR 1.16 per 10-year increase, 95% CI 1.10–1.22, high quality), congenital aetiology (HR 2.35, 95% CI 1.62 to 3.41, moderate quality), diabetes (HR 1.37, 95% CI 1.15 to 1.62, high quality), creatinine (HR 1.11 per 1 mg/dL increase, 95% CI 1.06 to 1.16, high quality), mechanical ventilation (HR 2.46, 95% CI 1.48 to 4.09, low quality) and short-term mechanical circulatory support (MCS) (HR 2.47, 95% CI 1.04 to 5.87, low quality) were significantly associated with 1-year mortality. Donor age (HR 1.20 per 10-year increase, 95% CI 1.14 to 1.26, high quality) and female donor to male recipient sex mismatch (HR 1.38, 95% CI 1.06 to 1.80, high quality) were significantly associated with 1-year mortality. None of the operative factors proved significant predictors.

    Conclusion

    High-quality and moderate-quality evidence demonstrates that recipient age, congenital aetiology, creatinine, pulsatile MCS, donor age and female donor to male recipient sex mismatch are associated with 1-year mortality post heart transplant. The results of this study should inform future guideline and predictive model development.




    Infective endocarditis in adults with congenital heart disease remains a lethal disease

    2018-01-03T06:35:31-08:00

    Objective

    Infective endocarditis (IE) is associated with significant morbidity and mortality. Patients with adult congenital heart disease (ACHD) have an increased risk of developing IE. The aim of this study is to describe the incidence, predictors of outcome and mortality associated with IE in ACHD in a contemporary cohort.

    Methods

    All episodes of IE in adults with congenital heart disease referred to our tertiary centre between 1999 and 2013 were included in the study. Patients were identified from the hospital database. The diagnosis of endocarditis was established according to the modified Duke criteria. The primary endpoint of the study was endocarditis-associated mortality.

    Results

    There were 164 episodes of IE in 144 patients (male 102, 70.8%). Mean age at presentation was 32.3±22.7 years. Out of these, 43% had a simple, 23% a moderate and 32% a complex lesion. It was at least the second bout of IE in 37 episodes (23%). A predisposing event could be identified in only 26.2% of episodes. Surgical intervention during the same admission was performed in 61 episodes (37.2%). During a median follow-up of 6.7 years (IQR 2.9–11.4), 28 (19.4%) patients died. Out of these, 10 deaths were related to IE (IE mortality 6.9%). On unvariate regression analysis, the development of an abscess (OR: 7.23; 95% CI 1.81 to 28.94, p<0.01) and age (OR: 1.05; 95% CI 1.01 to 1.10, p=0.03) were the only predictors of IE-associated mortality. There was no increase in IE cases at our centre during the period of the study.

    Conclusions

    IE-associated morbidity and mortality in a contemporary cohort of ACHD patients is still high in the current era.




    Myocardial revascularisation in high-risk subjects

    2018-01-03T06:35:31-08:00

    Learning objectives

  • Risk assessment in myocardial revascularisation

  • Complications of percutaneous and surgical revascularisation

  • The role of haemodynamic support

  • Introduction

    The synergistic effect of comorbidity, coronary artery lesion complexity and left ventricular (LV) systolic function can significantly increase the risk of adverse events at the time of myocardial revascularisation (figure 1). In patients with LV dysfunction and a large territory of ischaemia who have little reserve, further reductions in blood pressure can result in a spiral of haemodynamic compromise, culminating in cardiogenic shock or even death. In this article, we address factors that confer increased risk, current tools to quantify and guide revascularisation strategy in such patients; concluding with interventions to minimise risk including haemodynamic support devices, involvement of the heart team and technical considerations during procedural planning.

    Figure 1

    Factors increasing the risk of myocardial revascularisation. LMS, left main stem;...




    An abnormal structure of the left ventricle

    2018-01-03T06:35:31-08:00

    CLINICAL INTRODUCTION

    A 36-year-old man was referred for evaluation of an abnormal left ventricular (LV) structure found incidentally on transthoracic echocardiography (TTE) (figure 1). He had no symptoms except for mild palpitations. There was no significant medical history. Physical examination was unremarkable. ECG showed regular sinus rhythm with ST changes in lead II, III, avF and V6 (see online ). Cardiac magnetic resonance (CMR) (figure 1C) was performed. Treadmill exercise test did not demonstrate any electrocardiographic ischaemic changes. No arrhythmias were noted on Holter monitor. Which of the following is most likely the diagnosis?

    Figure 1

    Transthoracic echocardiography (TTE) and cardiac magnetic resonance (CMR). (A) Parasternal left ventricular longitudinal axis view of TTE; (B) colour Doppler of parasternal left ventricular longitudinal axis view of TTE; (C) left ventricular longitudinal axis view of CMR.

    Questions

    A: Lateral and inferolateral myocardial infarction

    B: Congenital absence of pericardium

    C: Pseudoaneurysm

    D: Congenital left ventricular outpouching