Browsing by Author "White, James A."

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    Determinants and Monitoring of Response to Disease-Modifying Therapy for Transthyretin Amyloidosis Cardiomyopathy: The ATTR-CM Therapy Study
    (2024-01-24) Shahi, Karan; Fine, Nowell M.; White, James A.; Howlett, Jonathan G.; Miller, Robert JH.
    Transthyretin amyloidosis cardiomyopathy (ATTR-CM) is a heart muscle disease characterized by the accumulation of misfolded transthyretin proteins as amyloid plaques in the myocardial interstitium. In 2020, tafamidis, a medication inhibiting the misfolding of transthyretin, received Health Canada's approval for treating ATTR-CM. However, substantial knowledge gaps persist in delivering optimal care and understanding predictors of response to tafamidis therapy. Over the past few years, there have been significant advancements in the clinical care of ATTR-CM. Improved diagnostic and staging techniques have resulted in higher rates of diagnosis, even among older patients not previously considered for invasive evaluation. Notably, tafamidis is the most expensive cardiovascular medication approved, with a list price of approximately $200,000 per patient per year. While Health Canada has defined criteria for initiating tafamidis, these are directly based on enrolment criteria for the international ATTR-ACT trial and may not fully reflect the current ATTR-CM patient population in the community. This project aimed to determine baseline predictors of adverse events in ATTR-CM patients treated with disease-modifying therapy, providing insights into determinants of prognosis and how markers of disease burden are serially impacted by treatment. The study's findings contribute to the development of evidence-based recommendations for guiding ATTR-CM disease monitoring and establish goals of therapy. These recommendations, rooted in evidence, seek to optimize patient care by offering a structured framework for monitoring ATTR-CM. Conducted as a retrospective cohort study, this research included 145 ATTR-CM patients followed by the Cardiac Amyloidosis Clinic, at the Libin Cardiovascular Institute (UofC). The results presented in this thesis contribute to an evidence-based approach for determining and monitoring the response to tafamidis therapy in ATTR-CM patients. The study reveals multiple parameters across clinical, biochemical, and cardiac imaging domains as predictors of major adverse outcomes (all-cause mortality, cardiovascular mortality and hospitalization). Tafamidis proves effective in attenuating disease progression, and specific baseline parameters can be used to assess variations in treatment. Importantly, initiating treatment during the early stages of the disease is pivotal, underscoring the critical role of early diagnosis. This conclusion emphasizes the imperative nature of timely intervention and ongoing observation in managing patients with ATTR-CM.
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    Electrocardiographic Parameters in the Assessment of Myocardial Fibrosis and Left Ventricular Systolic Function
    (2016) Narous, Mariam; Exner, Derek V.; Anderson, Todd J.; Fine, Nowell M.; White, James A.
    Assessment of cardiac structure and function is central to the care of patients with heart disease. Cardiac magnetic resonance (CMR) is the gold standard for such assessment, however it is expensive and oftentimes not readily accessible. We sought to evaluate the utility of electrocardiographic (ECG) and impedance-based parameters in estimating the amount of myocardial scar, left ventricular (LV) systolic function and myocardial deformation. Consecutive patients (n = 241; 42% female; mean age 55 years) undergoing clinical CMR and ECG assessments were recruited. ECG analysis was performed manually, using both the Modified Selvester Score (MSS) and the presence of fractionated QRS (fQRS) signals, and impedance testing using the Non-Invasive Cardiac System (NICaS). While MCS was of value, neither fQRS nor NICaS meaningfully predicted scar extent, LV systolic function. Or the amount of myocardial deformation. These results support additional investigation of the utility of the MSS in estimating cardiac structure and function among patients in whom cardiac imaging is clinically indicated.
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    Evidence-based cardiovascular magnetic resonance cost-effectiveness calculator for the detection of significant coronary artery disease
    (2022-01-06) Pandya, Ankur; Yu, Yuan-Jui; Ge, Yin; Nagel, Eike; Kwong, Raymond Y.; Bakar, Rafidah A.; Grizzard, John D.; Merkler, Alexander E.; Ntusi, Ntobeko; Petersen, Steffen E.; Rashedi, Nina; Schwitter, Juerg; Selvanayagam, Joseph B.; White, James A.; Carr, James; Raman, Subha V.; Simonetti, Orlando P.; Bucciarelli-Ducci, Chiara; Sierra-Galan, Lilia M.; Ferrari, Victor A.; Bhatia, Mona; Kelle, Sebastian
    Abstract Background Although prior reports have evaluated the clinical and cost impacts of cardiovascular magnetic resonance (CMR) for low-to-intermediate-risk patients with suspected significant coronary artery disease (CAD), the cost-effectiveness of CMR compared to relevant comparators remains poorly understood. We aimed to summarize the cost-effectiveness literature on CMR for CAD and create a cost-effectiveness calculator, useable worldwide, to approximate the cost-per-quality-adjusted-life-year (QALY) of CMR and relevant comparators with context-specific patient-level and system-level inputs. Methods We searched the Tufts Cost-Effectiveness Analysis Registry and PubMed for cost-per-QALY or cost-per-life-year-saved studies of CMR to detect significant CAD. We also developed a linear regression meta-model (CMR Cost-Effectiveness Calculator) based on a larger CMR cost-effectiveness simulation model that can approximate CMR lifetime discount cost, QALY, and cost effectiveness compared to relevant comparators [such as single-photon emission computed tomography (SPECT), coronary computed tomography angiography (CCTA)] or invasive coronary angiography. Results CMR was cost-effective for evaluation of significant CAD (either health-improving and cost saving or having a cost-per-QALY or cost-per-life-year result lower than the cost-effectiveness threshold) versus its relevant comparator in 10 out of 15 studies, with 3 studies reporting uncertain cost effectiveness, and 2 studies showing CCTA was optimal. Our cost-effectiveness calculator showed that CCTA was not cost-effective in the US compared to CMR when the most recent publications on imaging performance were included in the model. Conclusions Based on current world-wide evidence in the literature, CMR usually represents a cost-effective option compared to relevant comparators to assess for significant CAD.
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    Prevalence, incidence and clinical outcomes of epicardial coronary artery disease among transthyretin amyloidosis cardiomyopathy patients
    (2023-03-08) Hassan, Rana; Miller, Robert J. H.; Howlett, Jonathan G.; White, James A.; Fine, Nowell M.
    Abstract Background Transthyretin amyloidosis cardiomyopathy (ATTR-CM) patients are often older and may be at risk for obstructive epicardial coronary artery disease (oeCAD). While ATTR-CM may cause small vessel coronary disease, the prevalence and clinical significance of oeCAD is not well described. Methods and results The prevalence and incidence of oeCAD and its association with all-cause mortality and hospitalization among 133 ATTR-CM patients with ≥ 1-year follow-up was evaluated. The mean age was 78 ± 9 years, 119 (89%) were male, 116 (87%) had wild-type and 17 (13%) had hereditary subtypes. Seventy-two (54%) patients underwent oeCAD investigations, with 30 (42%) receiving a positive diagnosis. Among patients with a positive oeCAD diagnosis, 23 (77%) were diagnosed prior to ATTR-CM diagnosis, 6 (20%) at the time of ATTR-CM diagnosis, and 1 (3%) after ATTR-CM diagnosis. Baseline characteristics between patients with and without oeCAD were similar. Among patients with oeCAD, only 2 (7%) required additional investigations, intervention or hospitalization after ATTR-CM diagnosis. After a median follow-up of 27 months there were 37 (28%) deaths in the study population, including 5 patients with oeCAD (17%). Fifty-six (42%) patients in the study population required hospitalization, including 10 patients with oeCAD (33%). There was no significant difference in the rates of death or hospitalization among ATTR-CM patients with and without oeCAD, and oeCAD was not significantly associated with either outcome by univariable regression analysis. Conclusions While oeCAD is prevalent in ATTR-CM patients, this diagnosis is frequently known at time of ATTR-CM diagnosis and characteristics are similar to patients without oeCAD.
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    Right ventricular insertion site fibrosis in a dilated cardiomyopathy referral population: phenotypic associations and value for the prediction of heart failure admission or death
    (2021-06-17) Mikami, Yoko; Cornhill, Aidan; Dykstra, Steven; Satriano, Alessandro; Hansen, Reis; Flewitt, Jacqueline; Seib, Michelle; Rivest, Sandra; Sandonato, Rosa; Lydell, Carmen P.; Howarth, Andrew G.; Heydari, Bobak; Merchant, Naeem; Fine, Nowell; White, James A.
    Abstract Background Dilated cardiomyopathy (DCM) is increasingly recognized as a heterogenous disease with distinct phenotypes on late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) imaging. While mid-wall striae (MWS) fibrosis is a widely recognized phenotypic risk marker, other fibrosis patterns are prevalent but poorly defined. Right ventricular (RV) insertion (RVI) site fibrosis is commonly seen, but without objective criteria has been considered a non-specific finding. In this study we developed objective criteria for RVI fibrosis and studied its clinical relevance in a large cohort of patients with DCM. Methods We prospectively enrolled 645 DCM patients referred for LGE-CMR. All underwent standardized imaging protocols and baseline health evaluations. LGE images were blindly scored using objective criteria, inclusive of RVI site and MWS fibrosis. Associations between LGE patterns and CMR-based markers of adverse chamber remodeling were evaluated. Independent associations of LGE fibrosis patterns with the primary composite clinical outcome of heart failure admission or death were determined by multivariable analysis. Results The mean age was 56 ± 14 (28% female) with a mean left ventricular (LV) ejection fraction (LVEF) of 37%. At a median of 1061 days, 129 patients (20%) experienced the primary outcome. Any abnormal LGE was present in 306 patients (47%), inclusive of 274 (42%) meeting criteria for RVI site fibrosis and 167 (26%) for MWS fibrosis. All with MWS fibrosis showed RVI site fibrosis. Solitary RVI site fibrosis was associated with higher bi-ventricular volumes [LV end-systolic volume index (78 ± 39 vs. 66 ± 33 ml/m2, p = 0.01), RV end-diastolic volume index (94 ± 28 vs. 84 ± 22 ml/m2 (p < 0.01), RV end-systolic volume index (56 ± 26 vs. 45 ± 17 ml/m2, p < 0.01)], lower bi-ventricular function [LVEF 35 ± 12 vs. 39 ± 10% (p < 0.01), RV ejection fraction (RVEF) 43 ± 12 vs. 48 ± 10% (p < 0.01)], and higher extracellular volume (ECV). Patient with solitary RVI site fibrosis experienced a non-significant 1.4-fold risk of the primary outcome, increasing to a significant 2.6-fold risk when accompanied by MWS fibrosis. Conclusions RVI site fibrosis in the absence of MWS fibrosis is associated with bi-ventricular remodelling and intermediate risk of heart failure admission or death. Our study findings suggest RVI site fibrosis to be pre-requisite for the incremental development of MWS fibrosis, a more advanced phenotype associated with greater LV remodeling and risk of clinical events.