Tarun Mittal

Measurement of endothelial function and its clinical utility for cardiovascular risk.

Over the past two decades, the central role of the endothelium in the initiation, progression, and clinical sequelae of atherosclerosis has been increasingly recognized. Assessment of the pathobiology of the endothelium and its ability to act as a potential therapeutic target remains an area of active research interest. Whilst endothelial function has been shown to be a marker for risk of cardiovascular events in high-risk groups, there remains considerable debate about the most appropriate way to assess this. We discuss the different clinical methods to assess endothelial function, focusing on flow-mediated dilatation (FMD) of the brachial artery, highlighting the importance of using a standardized methodology, as well as discussing the clinical limitations of using FMD in individuals.

Role of Noninvasive Imaging in the Diagnosis of Cardiac Allograft Vasculopathy

Cardiac allograft vasculopathy (CAV) is common, with a prevalence of 52% at 10 years after transplantation, and represents a leading cause of death beyond the first year, responsible for approximately 15% of deaths annually.1 It is characterized by diffuse and concentric intimal proliferation, typically involving the intramural as well as epicardial coronary arteries. Its diagnosis is difficult to establish clinically because of denervation of the transplanted heart. Consequently, it presents late with silent myocardial infarction, progressive heart failure, or arrhythmic sudden death.2 Screening is therefore required for its early detection. Although coronary intravascular ultrasound (IVUS) is considered the gold-standard technique for detecting the anatomic features of CAV (Table 1), its broad clinical use in this context is limited by cost and lack of widespread expertise, and its evaluation is limited to epicardial vessels.3 Coronary angiography, performed annually or biannually, remains the most common clinical screening method.4 However, because of the diffuse nature of CAV with a lack of normal reference segments and the relatively late occurring luminal narrowing, the sensitivity of angiography is as low as 30% when compared with IVUS (Figure 1).5 As a result, complications frequently occur before disease is evident angiographically.6 Furthermore, angiography is associated with significant albeit uncommon complications (overall complication rate, 7.4/1000 procedures, including rates of 0.65/1000, 1.6/1000, and 0.72/1000 for cerebrovascular accidents, vascular complications, and death, respectively), is disliked by transplant recipients, is costly, and repeated studies are associated with an important cumulative radiation dose.7 View this table: Table 1. Stanford Classification of CAV Severity on IVUS Figure 1. Invasive assessment of cardiac allograft vasculopathy (CAV) in a patient with severe disease, highlighting the limited sensitivity of conventional coronary angiography. Although no left anterior descending (LAD) flow-limiting stenoses are seen on angiography ( A ), intravascular ultrasound ( B ) shows significant intimal thickening, measuring up to …

Cardiac Allograft Vasculopathy after Heart Transplantation: Electrocardiographically Gated Cardiac CT Angiography for Assessment

PURPOSE To evaluate the diagnostic accuracy of cardiac computed tomographic (CT) angiography without the use of β-blockers compared with that of invasive angiography for the detection of cardiac allograft vasculopathy (CAV) in heart transplant recipients. MATERIALS AND METHODS The study was approved by the research ethics committee and informed consent was obtained. Heart transplant recipients (n = 138) scheduled for routine invasive angiography were prospectively enrolled to undergo CT to evaluate coronary artery calcification and retrospectively gated cardiac CT angiography with a 64-section scanner. The cardiac CT angiographic images were systematically analyzed for image quality. Degree of CAV was assessed by using a 15-coronary segments model. The area under the receiver operating characteristic curve, sensitivity, specificity, and negative and positive predictive values of cardiac CT angiography for detection of CAV with any degree of stenosis and greater than or equal to 50% stenosis were calculated. RESULTS Coronary artery calcification was absent in 82 patients, five (6%) of whom had CAV with 50% or more stenosis. Interpretable image quality was obtained in 130 (96%) of the 136 patients who completed the study and 1900 (98%) of 1948 segments. At the patient level, cardiac CT angiography had an area under the receiver operating characteristic curve, sensitivity, specificity, and positive and negative predictive values of 0.880 (95% confidence interval: 0.819, 0.941), 98%, 78%, 77%, and 98%, respectively, for diagnosis of CAV with any degree of stenosis, but for CAV with 50% or more stenosis, the corresponding values were 0.942 (95% confidence interval: 0.885, 1.000), 96%, 93%, 72%, and 99%, respectively. None of the 61 patients with normal cardiac CT angiographic results had CAV on the basis of invasive angiographic images. CONCLUSION The study results show that cardiac CT angiography compares favorably with invasive angiography in detecting CAV in heart transplant recipients and may be a preferable screening technique because of its noninvasive nature. The absence of coronary artery calcification alone is not reliable enough for excluding CAV.

Truly stentless autologous pericardial aortic valve replacement: an alternative to standard aortic valve replacement.

OBJECTIVE The aim of this study was to determine the feasibility and durability of truly stentless aortic valve replacement using autologous pericardium sutured directly onto the aortic wall. METHODS Eleven patients (mean age, 55.9 years) requiring aortic valve replacement were recruited. A circular piece of pericardium about 8 cm in diameter was harvested and treated in 0.6% glutaraldehyde for 10 minutes. The aortic valve was excised and, with the use of specially designed instruments (CardioMend LLC, Santa Barbara, Calif), the sinotubular junction was sized and the pericardium was tailored to the required size and shape and then sutured directly onto the aortic wall. The reconstructed valve was assessed directly and by echocardiography at the end of the operation; it was assessed by echocardiography and cardiac magnetic resonance imaging at 6 months and yearly. Computed tomographic scan of the aortic valve to assess for valve calcification was performed at last follow-up. RESULTS Hospital mortality was 0%. Mean follow-up was 6.5 years (range, 5.3-7.5 years). Freedom from structural valve deterioration, thromboembolism, endocarditis and reoperation was 100%, 100%, 72.7%, and 63.6%, respectively. There were 4 reoperations at 4, 13, 15, and 46 months, 3 of them owing to endocarditis and 1 owing to technical failure noted at the time of surgery. The remaining 7 patients are alive and well with a mean New York Heart Association class of 1.3 and normally functioning aortic valves with no calcification. CONCLUSIONS Truly stentless aortic valve replacement using autologous pericardium sutured directly onto the aortic wall is safe and feasible and has excellent durability up to 7.5 years with no calcification.

Sarcoid heart disease

To this day the aetiology of sarcoidosis continues to elude definition. Partially as a consequence of this, little in the way of new therapies has evolved. The enigma of this condition is that, unusually for a disease with the potential for devastating consequences, many patients show spontaneous resolution and recover. Cardiac involvement can affect individuals of any age, gender or race and has a predilection for the conduction system of the heart. Heart involvement can also cause a dilated cardiomyopathy with consequent progressive heart failure. The most common presentation of this systemic disease is with pulmonary infiltration, but many cases will be asymptomatic and are detected on routine chest radiography revealing lymphadenopathy. Current advances lie in the newer methods of imaging and diagnosing this unusual heart disease. This review describes the pathology and diagnosis of this condition and the newer imaging techniques that have developed for determining cardiac involvement.

Predictors of paravalvular aortic regurgitation following self-expanding Medtronic CoreValve implantation: The role of annulus size, degree of calcification, and balloon size during pre-implantation valvuloplasty and implant depth

OBJECTIVES We sought to investigate the role of balloon size during pre-implantation valvuloplasty in predicting AR and optimal Medtronic CoreValve (MCS) implantation depth. BACKGROUND Paravalvular aortic regurgitation (AR) is common following MCS implantation. A number of anatomical and procedural variables have been proposed as determinants of AR including degree of valve calcification, valve undersizing and implantation depth. METHODS We conducted a multicenter retrospective analysis of 282 patients who had undergone MCS implantation with prior cardiac CT annular sizing between 2007 and 2011. Native valve minimum (Dmin), maximum (Dmax) and arithmetic mean (Dmean) annulus diameters as well as agatston calcium score were recorded. Nominal and achieved balloon size was also recorded. AR was assessed using contrast angiography at the end of each procedure. Implant depth was measured as the mean distance from the nadir of the non- and left coronary sinuses to the distal valve frame angiographically. RESULTS 29 mm and 26 mm MCS were implanted in 60% and 39% of patients respectively. The majority of patients (N=165) developed AR <2 following MCS implantation. AR ≥3 was observed in 16% of the study population. High agatston calcium score and Dmean were found to be independent predictors of AR ≥3 in multivariate analysis (P<0.0001). Nominal balloon diameter and the number of balloon inflations did not influence AR. However a small achieved balloon diameter-to-Dmean ratio (≤0.85) showed modest correlation with AR ≥3 (P=0.04). This observation was made irrespective of the degree of valve calcification. A small MCS size-to-Dmean ratio is also associated with AR ≥3 (P=0.001). A mean implantation depth of ≥8+2mm was also associated with AR ≥3. Implantation depth of ≥12 mm was associated with small MCS diameter-to-Dmean ratio and increased 30-day mortality. CONCLUSION CT measured aortic annulus diameter and agatston calcium score remain important predictors of significant AR. Other procedural predictors include valve undersizing and low implantation depth. A small achieved balloon diameter-to-Dmean ratio might also predict AR ≥3. Our findings confirm that a small achieved balloon size during pre-implantation valvuloplasty predicts moderate-severe AR in addition to previously documented factors.

Computational fluid dynamic study of hemodynamic effects on aortic root blood flow of systematically varied left ventricular assist device graft anastomosis design

OBJECTIVES To quantify the range of blood flow parameters in ascending aorta that can result from various angulations of outflow graft anastomosis of a left ventricular assist device (LVAD) to the aortic wall, as a means to understand the mechanism of aortic valve insufficiency. METHODS A realistic aorta model with LVAD anastomosis was generated from computed tomographic images of a patient. Based on this model, the LVAD anastomosis geometry parameters, such as anastomosis locations, inclination angle, and azimuthal angle (cross-sectional plane) of the graft, were varied, to create 21 models. With the assumption of no flow passing the aortic valve, and a constant flow rate from the LVAD cannula, computational fluid dynamics simulations were used to study the blood flow patterns in the ascending aorta. In addition, pulsatile flows were assumed in the LVAD cannula, with the aortic valve opened during peak systole, for 2 specific anastomosis configurations, to evaluate the influence of the pulsatile flow profile and the transvalvular flow on the aortic flow patterns. RESULTS Changes in the inclination angle, from 60° to 120°, or the azimuthal angle, from 90° to 120°, or moving from a lower to a higher anastomosis position, causes significant changes for all flow parameters. A lower anastomosis location, an inclination angle ≥90°, and an azimuthal angle of 60° or 120° are all capable of reducing blood flow stagnation in the aortic root and producing normal wall shear stress and moderate pressure values in the region. CONCLUSIONS Carefully chosen anastomosis geometry is likely to be able to generate a close-to-normal hemodynamic environment in the aortic root. Greater knowledge of aortic valve remodeling may make possible the creation of favorable flow patterns in the aortic root, through optimization of surgical design to reduce or delay the occurrence of aortic valve insufficiency.

The national evolution of cardiovascular CT practice: A UK NHS perspective

T.K. Mittal , E.D. Nicol ⁎, S.P. Harden , C.A. Roobottom , S.P. Padley , G. Roditi , C.R. Peebles , A. Taylor , M.C. Hamilton , G.J. Morgan-Hughes , R.W. Bury , on behalf of the British Society of Cardiovascular Imaging a Royal Brompton and Harefield NHS Foundation Trust, London, UK b University Hospital Southampton NHS Foundation Trust, Southampton, UK c Plymouth Hospitals NHS Trust, Plymouth, UK d Glasgow Royal Infirmary, Glasgow, UK e Centre for Cardiovascular Imaging, UCL Institute of Cardiovascular Science & Great Ormond Street Hospital, London, UK f Bristol Royal Infirmary, Bristol, UK g Blackpool Victoria Infirmary, Blackpool, UK

Cardiac sarcoidosis with delayed enhanced MRI

A 40 year old Asian male collapsed while attending a wedding in India. He initially assumed that his drinks had been “spiked”. He attended a hospital in India when further episodes of dizziness occurred. An ECG showed a brief run of a broad complex tachycardia. Haematology and biochemistry were normal as …

Cardiac sarcoidosis: diagnosis and management

Cardiac sarcoidosis is one of the most serious and unpredictable aspects of this disease state. Heart involvement frequently presents with arrhythmias or conduction disease, although myocardial infiltration resulting in congestive heart failure may also occur. The prognosis in cardiac sarcoidosis is highly variable, which relates to the heterogeneous nature of heart involvement and marked differences between racial groups. Electrocardiography and echocardiography often provide the first clue to the diagnosis, but advanced imaging studies using positron emission tomography and MRI, in combination with nuclear isotope perfusion scanning are now essential to the diagnosis and management of this condition. The identification of clinically occult cardiac sarcoidosis and the management of isolated and/or asymptomatic heart involvement remain both challenging and contentious. Corticosteroids remain the first treatment choice with the later substitution of immunosuppressive and steroid-sparing therapies. Heart transplantation is an unusual outcome, but when performed, the results are comparable or better than heart transplantation for other disease states. We review the epidemiology, developments in diagnostic techniques and the management of cardiac sarcoidosis.