Nowell M Fine

Recent Advances in Mammalian Target of Rapamycin Inhibitor Use in Heart and Lung Transplantation.

Abstract The mammalian target of rapamycin (mTOR) inhibitors sirolimus and everolimus are increasingly used in cardiothoracic transplantation. Several recent clinical trials have demonstrated their efficacy in combination with reduced cyclosporine dosing in de novo heart transplant recipients, in particular with everolimus. A number of other studies have demonstrated their efficacy for improving renal function and reducing calcineurin inhibitor use, attenuating cardiac allograft vasculopathy progression and reducing cytomegalovirus infections in maintenance heart transplant populations. A growing body of literature, including a small number of clinical trials, now describes the use mTOR inhibitors in lung transplant recipients. The benefits in this population include improved lung and renal function in limited studies. Considerably less evidence is available in pediatric heart transplantation, though similar indications in the maintenance therapy population have been described. The benefits of mTOR inhibitors must be weighed against the increased risk of adverse events and drug intolerance compared with other primary immunosuppressants, and discontinuation rates are particularly high in lung transplant recipients. The risks of surgical wound healing complications in transplant recipients receiving mTOR inhibitors previously or actively supported by mechanical circulatory support devices remains poorly described in the current literature. The current role and recent evidence for mTOR inhibitor use in heart and lung transplantation is examined in this review.

Recent Advances in Cardiovascular Imaging Relevant to the Management of Patients with Suspected Cardiac Amyloidosis.

Cardiac amyloidosis is a form of infiltrative cardiomyopathy typically presenting with progressive heart failure. The clinical presentation and morphological findings often overlap with other cardiovascular diseases, and frequently results in misdiagnosis and consequent under-reporting. Cardiovascular imaging is playing an increasingly important diagnostic and prognostic role in this referral population, and is reducing the reliance on endomyocardial biopsy as a confirmatory testing. Advancements across multiple cardiac imaging modalities, including echocardiography, magnetic resonance imaging, nuclear imaging, and computed tomography, are improving diagnostic accuracy and offering novel approaches to sub-type differentiation and prognostication. This review explores recent advancements in cardiac imaging for the diagnosis, typing, and staging of cardiac amyloidosis, with a focus on new and evolving techniques. Emphasis is also placed on the promise of non-invasive cardiac imaging to provide value across the spectrum of this clinical disease, from early disease identification (prior to the development of increased wall thickness) through to markers of advanced disease associated with early mortality.

Relative influence of peak strain delay and peak strain amplitude of non-scarred myocardium in response to cardiac resynchronization therapy: insights from segmental 4D strain analysis

Background The burden and location of replacement fibrosis by Late Gadolinium Enhancement (LGE) MRI is a recognized predictor of non-response in patients undergoing cardiac resynchronization therapy (CRT). However, the capacity of the non-scarred tissue to respond favorably is felt to be dependent upon incremental factors. In this study we explored the utility of 4D strain analysis of non-scarred myocardial tissue to predict response to CRT.

Do whole body impedance cardiography estimates of left ventricular structure, volumes and function correlate with the gold standard of cardiac magnetic resonance imaging?

Methods Consecutive patients (n = 204) undergoing a standard clinical CMR using either 1.5T or 3T MRI were enrolled. Whole-body impedance cardiography, using the Non-Invasive Cardiac System (NICaS), was performed within 14 days of the CMR. At least 5 consecutive NICaS measurements, calculated every 20 seconds, were averaged to estimate LV stroke volume (SV), cardiac output (CO) and the surrogate of an LV EF < 55% (i.e., Granov Goor Index < 10). Short axis cine imaging was performed in accordance with CMR Society guidelines. CMR and NICaS results were compared using linear regression. Bland-Altman (BA) plots were incrementally used to evaluate individual variability in modality correlation over the range of data observed. The capacity of NICaS to predict a CMR-based LV EF < 55% was determined via receiver operating characteristic curve (ROC) area under the curve (AUC) analysis. Results The study population included 85 (42%) women, had a mean age of 55 years and a mean CMR EF of 57% (range 22% to 82%). A modest, significant, linear correlation was found between NICaS and CMR LV SV (r = 0.34; p < 0.0001) (Figure 1), though there was substantial variability within subjects over the range of values (Figure 2). Similar results were observed between NICaS and CMR CO (r = 0.19; p = 0.007). No significant linear correlation between the NICaS estimate of LV EF and CMR LV EF was observed (r = 0.13; p = 0.07). There were 72 (35%) subjects with a CMR EF < 55%. ROC analysis showed an AUC for the NICaS LV EF surrogate of 0.53 for predicting a CMR LV EF < 55% with a sensitivity of 41% (95% CI: 30% to 53%) and specificity of 68% (95% CI: 59% to 76%).

Markers of abnormal tissue deformation and fibrosis in remote myocardium following acute myocardial infarction: a comparison of diabetics versus non-diabetics performed using spatially matched 4D strain and native T1 mapping

Markers of abnormal tissue deformation and fibrosis in remote myocardium following acute myocardial infarction: a comparison of diabetics versus non-diabetics performed using spatially matched 4D strain and native T1 mapping Alessandro Satriano, Kate Fenwick, Dexter D Waters, Haris Vaid, Yoko Mikami, Naeem Merchant, Carmen P Lydell, Andrew G Howarth, Teresa A Whitman, Derek V Exner, Bobak Heydari, Nowell M Fine, James A White

Segmental strain analysis by deformation of a mesh model: comparison of segmental strain metrics and late gadolinium enhancement quantification in myocardial infarction

Background The presence and transmurality of posterolateral scar within the left ventricle by late gadolinium enhancement (LGE) imaging has been shown to portend poor response to cardiac resynchronization therapy due to placement of the LV lead in this region. Unfortunately, the use of gadolinium is contraindicated in patients with significant renal dysfunction due to the risk of nephrogenic systemic fibrosis. Alternative measures of regional myocardial non-viability by 4D strain analysis may be highly useful for CRT evaluation in patients with heart failure and renal dysfunction.

Cardiovascular magnetic resonance imaging of cardiac remodeling and strain analysis in adolescent obesity

Background The increasing worldwide prevalence of childhood obesity portends the development of type 2 diabetes and cardiovascular disease (CVD) in this population. Cardiovascular Magnetic Resonance (CMR) imaging provides a sensitive imaging tool that may afford early detection of structural and functional alterations secondary to obesity. This pilot study explores the potential for CMR imaging, inclusive of left ventricular (LV) volume and mass analysis, Native T1 mapping and 4D strain analysis to identify such changes related to obesity in adolescence.

Refining the characterization of residual function in hypertrophic cardiomyopathy through remote segment 4D strain analysis

Background Quantitative assessment of late gadolinium enhancement (LGE) by cardiovascular magnetic resonance imaging (CMR) has been associated with an increased risk of sudden cardiac death (SCD) in patients with hypertrophic cardiomyopathy (HCM). However, patients with lesser degrees of LGE may still remain at high risk of adverse cardiac events due to the diffuse pathophysiology of HCM. Non-invasive characterization of the degree of biomechanical strain within non-enhanced myocardium may be a novel marker of disease in patients with HCM.

4D strain analysis within non-infarcted myocardium of patients with ischemic cardiomyopathy: potential marker for the prediction of adverse cardiac events

Background Adverse left ventricular remodeling following myocardial infarction (MI) remains one of the strongest prognostic indicators of adverse cardiac events. Increased wall stress and biomechanical strain within non-infarcted myocardium contribute to myocyte hypertrophy, fibrosis, and late adverse remodeling. This study aimed to demonstrate the feasibility of performing 4D strain analysis within noninfarcted myocardial segments through spatial registration to late gadolinium enhancement (LGE) imaging by cardiac magnetic resonance imaging (CMR) in ischemic cardiomyopathy (ICM) patients.