Advances in computational modelling for personalised medicine after myocardial infarction

Myocardial infarction (MI) is a leading cause of premature morbidity and mortality worldwide. Determining which patients will experience heart failure and sudden cardiac death after an acute MI is notoriously difficult for clinicians. The extent of heart damage after an acute MI is informed by cardiac imaging, typically using echocardiography or sometimes, cardiac magnetic resonance (CMR). These scans provide complex data sets that are only partially exploited by clinicians in daily practice, implying potential for improved risk assessment. Computational modelling of left ventricular (LV) function can bridge the gap towards personalised medicine using cardiac imaging in patients with post-MI. Several novel biomechanical parameters have theoretical prognostic value and may be useful to reflect the biomechanical effects of novel preventive therapy for adverse remodelling post-MI. These parameters include myocardial contractility (regional and global), stiffness and stress. Further, the parameters can be delineated spatially to correspond with infarct pathology and the remote zone. While these parameters hold promise, there are challenges for translating MI modelling into clinical practice, including model uncertainty, validation and verification, as well as time-efficient processing. More research is needed to (1) simplify imaging with CMR in patients with post-MI, while preserving diagnostic accuracy and patient tolerance (2) to assess and validate novel biomechanical parameters against established prognostic biomarkers, such as LV ejection fraction and infarct size. Accessible software packages with minimal user interaction are also needed. Translating benefits to patients will be achieved through a multidisciplinary approach including clinicians, mathematicians, statisticians and industry partners

Assessment of poststress left ventricular ejection fraction by gated SPECT: comparison with equilibrium radionuclide angiocardiography

PURPOSE: We compared left ventricular (LV) ejection fraction obtained by gated SPECT with that obtained by equilibrium radionuclide angiocardiography in a large cohort of patients. METHODS: Within 1 week, 514 subjects with suspected or known coronary artery disease underwent same-day stress-rest (99m)Tc-sestamibi gated SPECT and radionuclide angiocardiography. For both studies, data were acquired 30 min after completion of exercise and after 3 h rest. RESULTS: In the overall study population, a good correlation between ejection fraction measured by gated SPECT and by radionuclide angiocardiography was observed at rest (r=0.82, p<0.0001) and after stress (r=0.83, p<0.0001). In Bland-Altman analysis, the mean differences in ejection fraction (radionuclide angiocardiography minus gated SPECT) were -0.6% at rest and 1.7% after stress. In subjects with normal perfusion (n=362), a good correlation between ejection fraction measured by gated SPECT and by radionuclide angiocardiography was observed at rest (r=0.72, p<0.0001) and after stress (r=0.70, p<0.0001) and the mean differences in ejection fraction were -0.9% at rest and 1.4% after stress. Also in patients with abnormal perfusion (n=152), a good correlation between the two techniques was observed both at rest (r=0.89, p<0.0001) and after stress (r=0.90, p<0.0001) and the mean differences in ejection fraction were 0.1% at rest and 2.5% after stress. CONCLUSION: In a large study population, a good agreement was observed in the evaluation of LV ejection fraction between gated SPECT and radionuclide angiocardiography. However, in patients with perfusion abnormalities, a slight underestimation in poststress LV ejection fraction was observed using gated SPECT as compared to equilibrium radionuclide angiocardiography

Estimating prognosis in patients with acute myocardial infarction using personalized computational heart models

Biomechanical computational models have potential prognostic utility in patients after an acute ST-segment–elevation myocardial infarction (STEMI). In a proof-of-concept study, we defined two groups (1) an acute STEMI group (n = 6, 83% male, age 54 ± 12 years) complicated by left ventricular (LV) systolic dysfunction; (2) an age- and sex- matched hyper-control group (n = 6, 83% male, age 46 ± 14 years), no prior history of cardiovascular disease and normal systolic blood pressure (SBP &#60; 130 mmHg). Cardiac MRI was performed in the patients (2 days &#38; 6 months post-STEMI) and the volunteers, and biomechanical heart models were synthesized for each subject. The candidate parameters included normalized active tension (ATnorm) and active tension at the resting sarcomere length (Treq, reflecting required contractility). Myocardial contractility was inversely determined from personalized heart models by matching CMR-imaged LV dynamics. Compared with controls, patients with recent STEMI exhibited increased LV wall active tension when normalized by SBP. We observed a linear relationship between Treq 2 days post-MI and global longitudinal strain 6 months later (r = 0.86; p = 0.03). Treq may be associated with changes in LV function in the longer term in STEMI patients complicated by LV dysfunction. Further studies seem warranted

Assessment of the relationships between myocardial contractility and infarct tissue revealed by serial magnetic resonance imaging in patients with acute myocardial infarction

Imaging changes in left ventricular (LV) volumes during the cardiac cycle and LV ejection fraction do not provide information on regional contractility. Displacement ENcoding with Stimulated Echoes (DENSE) is a strain-encoded cardiac magnetic resonance (CMR) technique that measures strain directly. We investigated the relationships between strain revealed by DENSE and the presence and extent of infarction in patients with recent myocardial infarction (MI). 50 male subjects were invited to undergo serial CMR within 7 days of MI (baseline) and after 6 months (follow-up; n = 47). DENSE and late gadolinium enhancement (LGE) images were acquired to enable localised regional quantification of peak circumferential strain (Ecc) and the extent of infarction, respectively. We assessed: (1) receiver operating characteristic (ROC) analysis for the classification of LGE, (2) strain differences according to LGE status (remote, adjacent, infarcted) and (3) changes in strain revealed between baseline and follow-up. 300 and 258 myocardial segments were available for analysis at baseline and follow-up respectively. LGE was present in 130/300 (43 %) and 97/258 (38 %) segments, respectively. ROC analysis revealed moderately high values for peak Ecc at baseline [threshold 12.8 %; area-under-curve (AUC) 0.88, sensitivity 84 %, specificity 78 %] and at follow-up (threshold 15.8 %; AUC 0.76, sensitivity 85 %, specificity 64 %). Differences were observed between remote, adjacent and infarcted segments. Between baseline and follow-up, increases in peak Ecc were observed in infarcted segments (median difference of 5.6 %) and in adjacent segments (1.5 %). Peak Ecc at baseline was indicative of the change in LGE status between baseline and follow-up. Strain-encoded CMR with DENSE has the potential to provide clinically useful information on contractility and its recovery over time in patients with MI

Early diagnosis of cardiovascular diseases in workers: role of standard and advanced echocardiography

Cardiovascular disease (CVD) still remains the main cause of morbidity and mortality and consequently early diagnosis is of paramount importance. Working conditions can be regarded as an additional risk factor for CVD. Since different aspects of the job may affect vascular health differently, it is important to consider occupation from multiple perspectives to better assess occupational impacts on health. Standard echocardiography has several targets in the cardiac population, as the assessment of myocardial performance, valvular and/or congenital heart disease, and hemodynamics. Three-dimensional echocardiography gained attention recently as a viable clinical tool in assessing left ventricular (LV) and right ventricular (RV), volume, and shape. Two-dimensional (2DSTE) and, more recently, three-dimensional speckle tracking echocardiography (3DSTE) have also emerged as methods for detection of global and regional myocardial dysfunction in various cardiovascular diseases, and applied to the diagnosis of subtle LV and RV dysfunction. Although these novel echocardiographic imaging modalities have advanced our understanding of LV and RV mechanics, overlapping patterns often show challenges that limit their clinical utility. This review will describe the current state of standard and advanced echocardiography in early detection (secondary prevention) of CVD and address future directions for this potentially important diagnostic strategy

Ventricular function following myocardial infarction : the prognostic value of radionuclide ventriculography

Ventricular performance was assessed in one hundred consecutive patients recovering from their first myocardial infarction using the non-invasive technique of radionuclide ventriculography. This method was successfully performed in almost 100% of cases and repeated studies had a high degree of patient acceptability; the results were reproducible and easy to interpret and quantify with relative observer independence. Gated blood pool imaging performed prior to discharge from hospital revealed significant impairment of left ventricular function in the majority of patients, often when not clinically suspected. Those patients recovering from anterior infarction had greater reduction in left ventricular ejection fraction with a higher incidence of the more severe abnormalities of regional ventricular wall motion. A system of paradox imaging proved an accurate method for the detection of ventricular dyskinesis, present in 25% of all patients recovering from infarction. Subclinical right ventricular dysfunction occurred in over 40% of those recovering from inferior infarction and the variable degree of right ventricular necrosis contributed to enzymatic indices of infarct size accounting for the relative sparing of left ventricular function. Left ventricular failure and serious arrhythmia in the acute phase were both associated with marked reduction of ejection fraction in the convalescent phase. Low resting ejection fraction at discharge failed to improve in the subsequent year and was associated with the development of left ventricular failure, ventricular arrhythmia and sudden death. Reduction in ejection fraction during exercise testing performed four weeks after discharge had greater sensitivity and specificity than conventional electrocardiographic criteria in the prediction of the development of post-infarction angina which also carried a considerable risk of sudden death. The results of radionuclide ventriculography at rest and during exercise identified as "high risk" 11 of the 13 patients who were to die in the following year and proved more accurate than the Coronary Care Indices currently in use. The implications of these results are related to conventional clinical practice and the development of these and other radionuclide techniques to measure different parameters of ventricular function are discussed

The Impact of Myocardial Infarction on Ventricular Function

Eighty one patients were studied using radionuclide ventriculography to study the effects of myocardial infarction (36 anterior and 45 inferior) on ventricular function during the early and convalescent phases. Left and right ventricular function was assessed during hospitalisation on day 1, day 3 and at hospital discharge and repeated after a mean of 16+/-3 months following the index infarction. Chapter 1 is a review of the literature relating to the impact of acute myocardial infarction on ventricular function. This chapter is in 3 sections; the first two deal with the effects of myocardial infarction on global and regional left ventricular function, respectively, and the final section relates to the natural history of right ventricular function following myocardial infarction. Within each section the findings from animal experiments and early haemodynamic studies are reviewed first, followed by the findings of clinical studies which have mainly utilised non-invasive techniques to assess ventricular function. Chapter 2, "Methods", contains the details of the patient population studied, study design, statistical methods and the radionuclide techniques employed. Details regarding the use of Xenon-133 in the evaluation of right ventricular function and the analysis of regional ventricular function are dealt with in later chapters. Chapter 3, "The impact of acute myocardial infarction on global left ventricular function", presents the findings from the analysis of global left ventricular function during the hospitalisation phase. Anterior myocardial infarction was associated with lower ejection fractions than inferior myocardial infarction. Little variation was found in the left ventricular ejection fraction when patients were grouped according to the site of infarction. Variability in the left ventricular ejection fraction was found to occur in certain individuals and some patient subgroups. This did not appear to be related to any of the measured patient demographics or prognosis. A good correlation was found between the left ventricular ejection fraction and the size of infarction as estimated by Tl-201 scintigraphy. The correlation between the left ventricular ejection fraction and the enzymatic estimate of infarct size was closer following anterior in comparison with inferior infarction. The Killip and Norris classifications were not closely related to the left ventricular ejection fraction. A low left ventricular ejection fraction was associated with increased mortality; in addition the relationship between the left ventricular ejection fraction and mortality appeared to be influenced by the site of infarction. Chapter 4, "The impact of acute myocardial infarction on right ventricular function", deals with the data pertaining to right ventricular function obtained from gated technetium-99m equilibrium ventriculography during the hospitalisation phase. Right ventricular dysfunction was identified in 64% and 39% of patients following inferior and anterior infarction, respectively. No significant change in the right ventricular ejection fraction occurred following either anterior or inferior infarction during this period. Chapter 5, "Assessment of right ventricular function following acute inferior myocardial infarction using 133-Xenon imaging", presents the findings from the use of gated 133-Xenon imaging to assess right ventricular function acutely following acute inferior myocardial infarction. The use of this techniques overcomes many of the limitations of other techniques in the assessment of right ventricular function. Acute inferior myocardial infarction was found to result in a wide spectrum of right ventricular dysfunction. The right ventricular ejection fraction ranged from 7-54%, mean 30+/-11%. The findings were compared to clinical assessment of right ventricular function, and revealed that significant right ventricular dysfunction often goes undetected clinically. Chapter 6, "The natural history of ventricular function in the sixteen months following acute myocardial infarction", examines the course of left and right ventricular function during the convalescent phase (mean follow-up period 16+/-3 months). A slight improvement was observed in the left ventricular ejection fraction following inferior myocardial infarction. Chapter 8, "The relationship between the left ventricular ejection fraction and regional ventricular function", examines the relationship between alterations in the left ventricular function and regional ventricular function using the technique described in Chapter 7. No change was found in regional ventricular function following anterior myocardial infarction during the in-hospital phase. Chapter 9, "The impact of myocardial infarction on ventricular function", reviews the subject of ventricular function following myocardial infarction with reference to the major findings presented in this thesis and possible areas for future study are discussed

Infarct size and left ventricular remodelling after preventive percutaneous coronary intervention

Objective: We hypothesised that, compared with culprit-only primary percutaneous coronary intervention (PCI), additional preventive PCI in selected patients with ST-elevation myocardial infarction with multivessel disease would not be associated with iatrogenic myocardial infarction, and would be associated with reductions in left ventricular (LV) volumes in the longer term. Methods: In the preventive angioplasty in myocardial infarction trial (PRAMI; ISRCTN73028481), cardiac magnetic resonance (CMR) was prespecified in two centres and performed (median, IQR) 3 (1, 5) and 209 (189, 957) days after primary PCI. Results: From 219 enrolled patients in two sites, 84% underwent CMR. 42 (50%) were randomised to culprit-artery-only PCI and 42 (50%) were randomised to preventive PCI. Follow-up CMR scans were available in 72 (86%) patients. There were two (4.8%) cases of procedure-related myocardial infarction in the preventive PCI group. The culprit-artery-only group had a higher proportion of anterior myocardial infarctions (MIs) (55% vs 24%). Infarct sizes (% LV mass) at baseline and follow-up were similar. At follow-up, there was no difference in LV ejection fraction (%, median (IQR), (culprit-artery-only PCI vs preventive PCI) 51.7 (42.9, 60.2) vs 54.4 (49.3, 62.8), p=0.23), LV end-diastolic volume (mL/m2, 69.3 (59.4, 79.9) vs 66.1 (54.7, 73.7), p=0.48) and LV end-systolic volume (mL/m2, 31.8 (24.4, 43.0) vs 30.7 (23.0, 36.3), p=0.20). Non-culprit angiographic lesions had low-risk Syntax scores and 47% had non-complex characteristics. Conclusions: Compared with culprit-only PCI, non-infarct-artery MI in the preventive PCI strategy was uncommon and LV volumes and ejection fraction were similar

Microvascular resistance predicts myocardial salvage and infarct characteristics in ST-elevation myocardial infarction

&lt;b&gt;Background:&lt;/b&gt; The pathophysiology of myocardial injury and repair in patients with ST‐elevation myocardial infarction is incompletely understood. We investigated the relationships among culprit artery microvascular resistance, myocardial salvage, and ventricular function.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Methods and Results:&lt;/b&gt; The index of microvascular resistance (IMR) was measured by means of a pressure‐ and temperature‐sensitive coronary guidewire in 108 patients with ST‐elevation myocardial infarction (83% male) at the end of primary percutaneous coronary intervention. Paired cardiac MRI (cardiac magnetic resonance) scans were performed early (2 days; n=108) and late (3 months; n=96) after myocardial infarction. T2‐weighted‐ and late gadolinium–enhanced cardiac magnetic resonance delineated the ischemic area at risk and infarct size, respectively. Myocardial salvage was calculated by subtracting infarct size from area at risk. Univariable and multivariable models were constructed to determine the impact of IMR on cardiac magnetic resonance–derived surrogate outcomes. The median (interquartile range) IMR was 28 (17–42) mm Hg/s. The median (interquartile range) area at risk was 32% (24%–41%) of left ventricular mass, and the myocardial salvage index was 21% (11%–43%). IMR was a significant multivariable predictor of early myocardial salvage, with a multiplicative effect of 0.87 (95% confidence interval 0.82 to 0.92) per 20% increase in IMR; P&#60;0.001. In patients with anterior myocardial infarction, IMR was a multivariable predictor of early and late myocardial salvage, with multiplicative effects of 0.82 (95% confidence interval 0.75 to 0.90; P&#60;0.001) and 0.92 (95% confidence interval 0.88 to 0.96; P&#60;0.001), respectively. IMR also predicted the presence and extent of microvascular obstruction and myocardial hemorrhage.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusion:&lt;/b&gt; Microvascular resistance measured during primary percutaneous coronary intervention significantly predicts myocardial salvage, infarct characteristics, and left ventricular ejection fraction in patients with ST‐elevation myocardial infarction.&lt;p&gt;&lt;/p&gt