The Cardiac Amyloidosis Registry Study (CARS): Rationale, Design and Methodology.

BACKGROUND: CARS (Cardiac Amyloidosis Registry Study) is a multicenter registry established in 2019 that includes patients with transthyretin (ATTR, wild-type and variant) and light chain (AL) cardiac amyloidosis (CA) evaluated at major amyloidosis centers between 1997 and 2025. CARS aims to describe the natural history of CA with attention to clinical and diagnostic variables at the time of diagnosis, real-world treatment patterns, and associated outcomes of patients in a diverse cohort that is more representative of the at-risk population than that described in CA clinical trials. METHODS AND RESULTS: This article describes the design and methodology of CARS, including procedures for data collection and preliminary results. As of February 2023, 20 centers in the United States enrolled 1415 patients, including 1155 (82%) with ATTR and 260 (18%) with AL CA. Among those with ATTR, wild-type is the most common ATTR (71%), and most of the 305 patients with variant ATTR have the p.V142I mutation (68%). A quarter of the total population identifies as Black. More individuals with AL are female (39%) compared to those with ATTR (13%). CONCLUSIONS: CARS will answer crucial clinical questions about CA natural history and permit comparison of different therapeutics not possible through current clinical trials. Future international collaboration will further strengthen the validity of observations of this increasingly recognized condition.

Diagnostic accuracy of bone scintigraphy imaging for transthyretin cardiac amyloidosis: systematic review and meta-analysis.

BACKGROUND: Bone scintigraphy imaging is frequently used to investigate patients with suspected transthyretin cardiac amyloidosis (ATTR-CM). However, the reported accuracy for interpretation approaches has changed over time. We performed a systematic review and meta-analysis to determine the diagnostic accuracy of visual planar grading, heart-to-contralateral (HCL) ratio, and quantitative analysis of SPECT imaging and evaluate reasons for shifts in reported accuracy. METHODS: We performed a systematic review to identify studies of the diagnostic accuracy of bone scintigraphy for ATTR-CM from 1990 until February 2023 using PUBMED and EMBASE. Studies were reviewed separately by two authors for inclusion and for risk of bias assessment. Summary receiver operating characteristic curves and operating points were determined with hierarchical modeling. RESULTS: Out of a total of 428 identified studies, 119 were reviewed in detail and 23 were included in the final analysis. The studies included a total of 3954 patients, with ATTR-CM diagnosed in 1337 (39.6%) patients and prevalence ranging from 21 to 73%. Visual planar grading and quantitative analysis had higher diagnostic accuracy (.99) than HCL ratio (.96). Quantitative analysis of SPECT imaging had the highest specificity (97%) followed by planar visual grade (96%) and HCL ratio (93%). ATTR-CM prevalence accounted for some of the observed between study heterogeneity. CONCLUSIONS: Bone scintigraphy imaging is highly accurate for identifying patients with ATTR-CM, with between study heterogeneity in part explained by differences in disease prevalence. We identified small differences in specificity, which may have important clinical implications when applied to low-risk screening populations.

Prevalence, incidence and clinical outcomes of epicardial coronary artery disease among transthyretin amyloidosis cardiomyopathy patients.

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.

Characteristics of Carpal Tunnel Syndrome in Wild-Type Transthyretin Amyloidosis.

BACKGROUND: Carpal tunnel syndrome (CTS) is one of the most common extra-cardiac manifestations of wild-type transthyretin amyloidosis (wtATTR); however, the characteristics of CTS in this population remain poorly understood. METHODS: This retrospective cohort study reports findings from a single-centre experience of comprehensive neurological screening at the time of wtATTR diagnosis by nerve conduction studies (NCS) and neurologist assessment. RESULTS: Seventy-nine patients underwent neurological screening, 73 (92%) males, mean age 79.2 ± 7.5 years. Seventy-four (94%) had electrodiagnostic findings of median neuropathy at the wrist (MNW), 37 (50%) of which had a prior diagnosis of CTS and 37 (50%) had a new diagnosis of MNW. Over half of wtATTR patients (42, 53%) had bilateral MNW on screening. Most with pre-existing CTS had bilateral disease (28, 76%) and underwent bilateral carpal tunnel release (CTR) (23, 62%) prior to screening. Twenty-one (19%) wrists had mild MNW, 43 (38%) moderate and 49 (43%) severe. Twenty-one (28%) wtATTR patients with MNW were asymptomatic, 10 of which (48%) had moderate disease. Nineteen (36%) wtATTR patients with symptomatic MNW had recurrent disease despite previous CTR. As a result of screening, 36 (68%) patients with symptomatic MNW were referred for CTR. CONCLUSIONS: MNW is exceptionally common at the time of wtATTR diagnosis, affecting 94% of our patients. Most had severe, bilateral MNW on NCS. Some were asymptomatic, despite having moderate disease. The rate of recurrence following CTR was observed to be higher in wtATTR patients than the general population.

The Incidence and Prevalence of Cardiac Amyloidosis in a Large Community-Based Cohort in Alberta, Canada.

BACKGROUND: Despite the improved awareness of cardiac amyloidosis among clinicians, its incidence and prevalence is not well-described in a community setting. We sought to investigate the incidence and prevalence of cardiac amyloidosis in the community. METHODS AND RESULTS: In the adult population of Alberta, we examined 3 cohorts: (1) probable cases of cardiac amyloidosis: the presence of physician-assigned diagnosis of amyloidosis (International Classification of Diseases [ICD]-10 code E85; ICD-9 277.3) and 1 or more health care encounter for heart failure (HF) (ICD-10 I50; ICD-9 428); (2) possible cardiac amyloidosis: the presence of clinical phenotypes suggestive of amyloidosis; and (3) a comparator HF cohort without amyloidosis. Between 2004 and 2018, 982 of the 145,329 patients with HF were identified as probable cardiac amyloidosis. During the same period, the incidence rates of probable cardiac amyloidosis increased from 1.38 to 3.69 per 100,000 person-years and the prevalence rates increased from 3.42 to 14.85 per 100,000 person-years (Ptrend < .0001). Patients with probable cardiac amyloidosis were more likely to be male, have a higher comorbidity burden, greater health care use, and poorer outcomes as compared with patients with HF without amyloidosis. A much larger group of patients was identified as possible cardiac amyloidosis (n = 46,255), with similar increase in prevalence from 2004 to 2018 (from 416 to 850 per 100,000 person-years). CONCLUSIONS: The incidence and prevalence of cardiac amyloidosis has increased over the last decade. Given the advent of new therapies for cardiac amyloidosis and considering their high cost, it is imperative to devise strategies to screen, identify, and track patients with cardiac amyloidosis from administrative databases.

Amyloidosis and COVID-19: experience from an amyloid program in Canada.

Severe acute respiratory syndrome coronavirus (SARS-CoV2) and associated COVID-19 infection continue to impact patients globally. Patients with underlying health conditions are at heightened risk of adverse outcomes from COVID-19; however, research involving patients with rare health conditions remains scarce. The amyloidoses are a rare grouping of protein deposition diseases. Light-chain and transthyretin amyloidosis are the most common disease forms, often present with systemic involvement of vital organs including the heart, nerves, kidneys, and GI tracts of affected individuals. The Amyloidosis Program of Calgary examined 152 ATTR patients and 103 AL patients analyzing rates of vaccination, COVID-19 testing, infection outcomes, influence referrals, and excess deaths. Results showed 15 total PCR-confirmed COVID-19 infections in the tested population of amyloid patients, with a higher frequency of infections among patient with AL compared to the ATTR cohort (26.2% vs 5.1%). Four patients (26.6%) required hospital admission for COVID-19 infection, 2 ATTR, and 2 AL patients. Of the confirmed cases, 1 (0.07%) unvaccinated ATTR patient died of a COVID-19 infection. An excess of deaths was found in both the ATTR and AL cohorts when comparing pre-pandemic years 2018 and 2019 to the pandemic years of 2020 and 2021. The finding suggests that amyloidosis patients are likely at a high risk for severe COVID-19 infection and mortality, especially those of advanced age, those on an active treatment with chemotherapy, and those with concomitant B-cell or plasma cell disorder. The impact of virtual healthcare visits and pandemic measures on the excess of deaths observed requires further research.

Quantitative technetium pyrophosphate and cardiovascular magnetic resonance in patients with suspected cardiac amyloidosis.

BACKGROUND: Quantitation of myocardial 99m Tc-pyrophosphate activity may have high diagnostic accuracy, but its correlation with disease burden is unknown. We examined the relationship between 99m Tc-pyrophosphate quantitation and cardiac magnetic resonance (CMR) measures in patients with suspected transthyretin cardiac amyloidosis (ATTR-CM) or light chain cardiac amyloidosis (AL-CM). METHODS: Consecutive patients who underwent 99mTc-pyrophosphate imaging and CMR were included. ATTR-CM and AL-CM were diagnosed using standard criteria. 99mTc-pyrophosphate images were assessed with standard parameters and quantified with cardiac pyrophosphate activity (CPA) and volume of involvement (VOI). We assessed the association between 99mTc-pyrophosphate image interpretation and CMR tissue characteristics. RESULTS: Seventy patients were identified, mean age 70.4 ± 11.4 years, with ATTR-CM and AL-CM diagnosed in 22 (31%) and 11 (16%) patients, respectively. In patients with ATTR-CM, there were significant correlations between CPA (r2 = 0.509, P < 0.001) and VOI (r2 = 0.586, P < 0.001) with native myocardial T1 mapping values. Additionally, CPA (adjusted hazard ratio (aHR) 1.04, P = 0.016), VOI (aHR 1.12, P = 0.034), and average myocardial T1 (aHR 1.12, P = 0.025) were associated with incidence of heart failure hospitalization or death. CONCLUSION: CPA and VOI were correlated with CMR measures of myocardial fibrosis in patients with ATTR-CM. 99mTc-pyrophosphate quantitation may have a role in ATTR-CM disease staging, guiding treatment, or following response to therapy.

Canadian Guidelines for Hereditary Transthyretin Amyloidosis Polyneuropathy Management.

Hereditary transthyretin-mediated (hATTR) amyloidosis is a progressive disease caused by mutations in the TTR gene leading to multisystem organ dysfunction. Pathogenic TTR aggregation, misfolding, and fibrillization lead to deposition of amyloid in multiple body organs and frequently involve the peripheral nerve system and the heart. Common neurologic manifestations include: sensorimotor polyneuropathy (PN), autonomic neuropathy, small-fiber PN, and carpal tunnel syndrome. Many patients have significant progression due to diagnostic delays as hATTR PN is not considered within the differential diagnosis. Recently, two effective novel disease-modifying therapies, inotersen and patisiran, were approved by Health Canada for the treatment of hATTR PN. Early diagnosis is crucial for the timely introduction of these disease-modifying treatments that reduce impairments, improve quality of life, and extend survival. In this guideline, we aim to improve awareness and outcomes of hATTR PN by making recommendations directed to the diagnosis, monitoring, and treatment in Canada.

Lignes directrices sur la prise en charge de l'amylose héréditaire à transthyrétine, accompagnée de polyneuropathie, au Canada.L'amylose héréditaire à transthyrétine (ATTRh) est une maladie évolutive, causée par des mutations du gène de la transthyrétine (TTR), qui entraînent un dysfonctionnement plurisystémique. L'agrégation, le mauvais repliement et la fibrillisation pathogènes de la TTR aboutissent au dépôt de protéines amyloïdes dans plusieurs organes, et affectent souvent le système nerveux périphérique et le cœur. Les troubles neurologiques fréquents comprennent une polyneuropathie sensorimotrice (PN), une neuropathie autonome, une polyneuropathie des petites fibres et le syndrome du canal carpien. Chez bon nombre de patients, la maladie a connu une évolution importante en raison de la pose tardive du diagnostic, la PN-ATTRh ne faisant pas l'objet d'un diagnostic différentiel. Santé Canada a approuvé, depuis peu, deux nouveaux médicaments modificateurs de la PN-ATTRh et efficaces contre l'affection, soit l'inotersen et le patisiran. La pose précoce du diagnostic revêt une importance cruciale dans l'instauration, en temps opportun, de ces tout nouveaux traitements qui atténuent les troubles, améliorent la qualité de vie et prolongent la survie. Les auteurs, par l'élaboration de la nouvelle ligne directrice, espèrent sensibiliser la communauté médicale à la PN-ATTRh, et améliorer les résultats cliniques qui y sont associés, en formulant des recommandations sur le diagnostic et le traitement de la maladie au Canada ainsi que sur la surveillance de son évolution.

Identification of cell-free DNA methylation patterns unique to the human left ventricle as a potential indicator of acute cellular rejection.

Increased levels of donor-derived cell-free DNA (dd-cfDNA) in recipient plasma have been associated with rejection after transplantation. DNA sequence differences have been used to distinguish between donor and recipient, but epigenetic differences could also potentially identify dd-cfDNA. This pilot study aimed to identify ventricle-specific differentially methylated regions of DNA (DMRs) that could be detected in cfDNA. We identified 24 ventricle-specific DMRs and chose two for further study, one on chromosome 9 and one on chromosome 12. The specificity of both DMRs for the left ventricle was confirmed using genomic DNA from multiple human tissues. Serial matched samples of myocardium (n = 33) and plasma (n = 24) were collected from stable adult heart transplant recipients undergoing routine endomyocardial biopsy for rejection surveillance. Plasma DMR levels increased with biopsy-proven rejection grade for individual patients. Mean cellular apoptosis in biopsy samples increased significantly with rejection severity (2.4%, 4.4% and 10.0% for ACR 0R, 1R, and 2R, respectively) but did not show a consistent relationship with DMR levels. We identified multiple DNA methylation patterns unique to the human ventricle and conclude that epigenetic differences in cfDNA populations represent a promising alternative strategy for the non-invasive detection of rejection.

Right ventricular insertion site fibrosis in a dilated cardiomyopathy referral population: phenotypic associations and value for the prediction of heart failure admission or death.

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.

Diagnostic and prognostic value of Technetium-99m pyrophosphate uptake quantitation for transthyretin cardiac amyloidosis.

BACKGROUND: 99mTc-pyrophosphate imaging has emerged as an important non-invasive method to diagnose transthyretin cardiac amyloidosis (ATTR-CM). Quantitation of 99mTc-pyrophosphate activity, on SPECT images, could be a marker of ATTR-CM disease burden. We assessed the diagnostic accuracy and clinical significance of 99mTc-pyrophosphate quantitation. METHODS AND RESULTS: Patients who underwent 99mTc-pyrophosphate imaging for suspected ATTR-CM were included. Using SPECT images, radiotracer activity in the myocardium was calculated using cardiac pyrophosphate activity (CPA) and volume of involvement (VOI), with thresholds for abnormal activity derived from LVBP activity. Diagnostic accuracy was assessed using area under the receiver operating characteristic curve (AUC). In total, 124 patients were identified, mean age 73.9 ± 11.4, with ATTR-CM diagnosed in 43 (34.7%) patients. CPA had the highest diagnostic accuracy (AUC .996, 95% CI .987-1.00), and was significantly higher compared to the Perugini score (AUC .952, P = .016). In patients with ATTR-CM, CPA was associated with reduced left ventricular ejection fraction (adjusted odds ratio 1.28, P = .035) and heart failure hospitalizations (adjusted hazard ratio 1.29, P = .006). CONCLUSION: Quantitative assessment of myocardial radiotracer activity with CPA or VOI have high diagnostic accuracy for ATTR-CM. Both measures are potential non-invasive markers to follow progression of disease or response to therapy.

Utility of Neuropathy Screening for Wild-Type Transthyretin Amyloidosis Patients.

BACKGROUND: Wild-type transthyretin amyloidosis (wtATTR) is an important cause of heart failure (HF); however, the prevalence and clinical significance of neurologic complications remains uncertain. METHODS: This analysis reports findings from a single-centre experience of routine neuropathy screening at the time of wtATTR diagnosis by nerve conduction studies and neurologist assessment, compared with age-matched controls. RESULTS: Forty-one wtATTR patients were included, 39 (95%) males, mean age 78.4 ± 7.7 years, 22 (54%) New York Heart Association (NYHA) class III-IV HF, along with 15 age-matched controls (mean age 77.1 ± 4.2 years, 80% male). Twenty-one (51%) wtATTR patients were diagnosed with polyneuropathy, 15 (37%) with spinal stenosis, 36 (88%) with carpal tunnel syndrome (CTS) and 14 (34%) with ulnar neuropathy. Comparison diagnoses among controls were 1 (7%), 0, 1 (7%) and 3 (20%), respectively. Among patients with NYHA class III-IV HF, 16 (73%) had polyneuropathy compared with 5 (26%) with class I-II (p < 0.01), odds ratio of 7.5 (95% confidence interval 1.9-29.9). After neuropathy screening, 19 (46%) patients were offered neurologic therapy and/or additional diagnostic evaluation. This included CTS release surgery (16, 39%), neuropathic pain medication (3, 7%), nerve block (1, 2%), wrist splinting (2, 5%) and foot care (1, 2%). Spine imaging was performed for 3 (7%) patients, and deltoid muscle and sural nerve biopsy for 1 (2%) patient. CONCLUSIONS: Screening of wtATTR patients for neurologic complications resulted in a management change for nearly half. CTS, polyneuropathy and ulnar neuropathy were common. This approach warrants consideration as part of routine assessment for newly diagnosed wtATTR patients.

Enhancing ICD-Code-Based Case Definition for Heart Failure Using Electronic Medical Record Data.

BACKGROUND: Surveillance and outcome studies for heart failure (HF) require accurate identification of patients with HF. Algorithms based on International Classification of Diseases (ICD) codes to identify HF from administrative data are inadequate owing to their relatively low sensitivity. Detailed clinical information from electronic medical records (EMRs) is potentially useful for improving ICD algorithms. This study aimed to enhance the ICD algorithm for HF definition by incorporating comprehensive information from EMRs. METHODS: The study included 2106 inpatients in Calgary, Alberta, Canada. Medical chart review was used as the reference gold standard for evaluating developed algorithms. The commonly used ICD codes for defining HF were used (namely, the ICD algorithm). The performance of different algorithms using the free text discharge summaries from a population-based EMR were compared with the ICD algorithm. These algorithms included a keyword search algorithm looking for HF-specific terms, a machine learning-based HF concept (HFC) algorithm, an EMR structured data based algorithm, and combined algorithms (the ICD and HFC combined algorithm). RESULTS: Of 2106 patients, 296 (14.1%) were patients with HF as determined by chart review. The ICD algorithm had 92.4% positive predictive value (PPV) but low sensitivity (57.4%). The EMR keyword search algorithm achieved a higher sensitivity (65.5%) than the ICD algorithm, but with a lower PPV (77.6%). The HFC algorithm achieved a better sensitivity (80.0%) and maintained a reasonable PPV (88.9%) compared with the ICD algorithm and the keyword algorithm. An even higher sensitivity (83.3%) was reached by combining the HFC and ICD algorithms, with a lower PPV (83.3%). The structured EMR data algorithm reached a sensitivity of 78% and a PPV of 54.2%. The combined EMR structured data and ICD algorithm had a higher sensitivity (82.4%), but the PPV remained low at 54.8%. All algorithms had a specificity ranging from 87.5% to 99.2%. CONCLUSIONS: Applying natural language processing and machine learning on the discharge summaries of inpatient EMR data can improve the capture of cases of HF compared with the widely used ICD algorithm. The utility of the HFC algorithm is straightforward, making it easily applied for HF case identification.

Frequency, predictors, and prognosis of ejection fraction improvement in heart failure: an echocardiogram-based registry study.

AIMS: To identify variables predicting ejection fraction (EF) recovery and characterize prognosis of heart failure (HF) patients with EF recovery (HFrecEF). METHODS AND RESULTS: Retrospective study of adults referred for ≥2 echocardiograms separated by ≥6 months between 2008 and 2016 at the two largest echocardiography centres in Alberta who also had physician-assigned diagnosis of HF. Of 10 641 patients, 3124 had heart failure reduced ejection fraction (HFrEF) (EF ≤ 40%) at baseline: while mean EF declined from 30.2% on initial echocardiogram to 28.6% on the second echocardiogram in those patients with persistent HFrEF (defined by <10% improvement in EF), it improved from 26.1% to 46.4% in the 1174 patients (37.6%) with HFrecEF (defined by EF absolute improvement ≥10%). On multivariate analysis, female sex [adjusted odds ratio (aOR) 1.66, 95% confidence interval (CI) 1.40-1.96], younger age (aOR per decade 1.16, 95% CI 1.09-1.23), atrial fibrillation (aOR 2.00, 95% CI 1.68-2.38), cancer (aOR 1.52, 95% CI 1.03-2.26), hypertension (aOR 1.38, 95% CI 1.18-1.62), lower baseline ejection fraction (aOR per 1% decrease 1.07 (1.06-1.08), and using hydralazine (aOR 1.69, 95% CI 1.19-2.40) were associated with EF improvements ≥10%. HFrecEF patients demonstrated lower rates per 1000 patient years of mortality (106 vs. 164, adjusted hazard ratio, aHR 0.70 [0.62-0.79]), all-cause hospitalizations (300 vs. 428, aHR 0.87 [0.79-0.95]), all-cause emergency room (ER) visits (569 vs. 799, aHR 0.88 [0.81-0.95]), and cardiac transplantation or left ventricular assist device implantation (2 vs. 10, aHR 0.21 [0.10-0.45]) compared to patients with persistent HFrEF. Females with HFrEF exhibited lower mortality risk (aHR 0.94 [0.88-0.99]) than males after adjusting for age, time between echocardiograms, clinical comorbidities, medications, and whether their EF improved or not during follow-up. CONCLUSION: HFrecEF patients tended to be younger, female, and were more likely to have hypertension, atrial fibrillation, or cancer. HFrecEF patients have a substantially better prognosis compared to those with persistent HFrEF, even after multivariable adjustment, and female patients exhibit lower mortality risk than men within each subgroup (HFrecEF and persistent HFrEF) even after multivariable adjustment.

Clinical Experience With the Use of Doxycycline and Ursodeoxycholic Acid for the Treatment of Transthyretin Cardiac Amyloidosis.

BACKGROUND: The tolerability and utility of combination doxycycline and ursodeoxycholic acid (ursodiol) amyloid fibril disruption therapy for transthyretin cardiac amyloidosis (ATTR CA) in clinical practice is poorly described. METHODS AND RESULTS: We report the clinical experience of 53 ATTR CA patients treated with doxycycline and ursodiol. Six patients (11%) did not tolerate the therapy owing to dermatologic and gastrointestinal effects. Of those remaining, the median follow-up was 22 months (range 8-30), mean age was 71 ± 11years, 41 (87%) were male, and 42 (89%) had wild-type and 5 (11%) mutant ATTR. Five patients (11%) died during follow-up. There was no significant change in New York Heart Association (NYHA) functional class, cardiac biomarkers, or echocardiographic parameters during follow-up. Left ventricular (LV) global longitudinal systolic strain (GLS) improved in 16 patients (38%) (-12 ± 4% to -17 ± 4%; P < .01). Patients whose LV GLS improved were significantly younger and had lower NYHA functional class, troponin-T, N-terminal pro-B-type natriuretic peptide (BNP), and baseline LV GLS levels compared with those whose LV GLS did not improve. Troponin-T improved in follow-up for patients whose LV GLS improved (35 ± 21 to 20 ± 14 ng/L; P = .06). CONCLUSIONS: Doxycycline and ursodiol therapy for treatment of ATTR CA was tolerable and was associated with stabilized markers of disease progression. LV GLS improved in patients with less advanced disease.

Delayed dehiscence of modified mechanical Bentall 7 years postsurgery for Takayasu's arteritis.

Following aortic surgery for vasculitis, the incidence and duration of onset of anastomotic breakdown is unclear. A case is presented of a young female patient with Takayasu's arteritis (TA) who was found to have frank dehiscence of a modified Bentall repair 7 years after surgery. The case highlights (i) the lack of normal healing following aortic surgery in TA, and (ii) need to differentiate imaging protocols for patients with defined vasculitis as opposed to degenerative aortic conditions. A recommendation is made for appropriate surveillance imaging modality alternating between computed tomography and magnetic resonance imaging in the often young patient population affected by vasculitis.

Implementation of a Multidisciplinary Inpatient Cardiology Service to Improve Heart Failure Outcomes in Guyana.

BACKGROUND: Guyana is a small developing country with a high burden of cardiovascular disease and extensive barriers to optimal care delivery. We investigated the effectiveness of a newly established multidisciplinary inpatient cardiology service in this setting. METHODS: We performed an interrupted time-series cohort study of heart failure (HF) patients admitted to the Georgetown Public Hospital Corporation from January to December 2015 and July 2016 to December 2017. The primary outcome was discharge on guideline-directed medical therapy (GDMT). Secondary outcomes included length of hospitalization and all-cause mortality. RESULTS: We identified 740 patients, 347 (46.9%) of whom were admitted after service implementation. The postimplementation cohort was more likely to be discharged on a beta-blocker (66.6% vs 41.7%; P < .01) and mineralocorticoid receptor antagonist (31.7% vs 15.3%; P = .01). They were also more likely to undergo echocardiography (60.8% vs 40.5%; P < .01) and chest x-rays (70.6% vs 46.6%; P < .01). Hospitalization length (10.0 ± 13.1 vs 9.8 ± 10.1 days) and readmissions within 90 days (19.0% vs 19.1%) were not significantly different. There were fewer deaths in the postimplementation cohort compared with the preimplementation cohort (12/347 vs 28/393). CONCLUSIONS: Establishment of a multidisciplinary inpatient cardiology service demonstrated increased adherence to GDMT without extending length of hospitalization.

Right ventricular strain: measurement and clinical application.

PURPOSE OF REVIEW: Right ventricular (RV) assessment has long been challenging and technically difficult using echocardiography. This is mainly the result of the asymmetrical shape of the RV making it difficult to visualize on one-or-two dedicated views, thus requiring multiple integrated views and subjective assessment. Measurement of tricuspid annular systolic plane excursion and RV tissue Doppler velocity have become relied-upon methods of objective assessments; however, have limitations for characterizing true RV physiology. RECENT FINDINGS: Studies suggest that two-dimensional RV free wall longitudinal systolic strain (RVFWS) using speckle-tracking echocardiography has emerged as a reproducible, feasible and highly prognostic technique for quantifying RV function. This has been demonstrated for patients with heart failure, ischemic heart disease, pulmonary hypertension, infiltrative disease and many other types of cardiovascular disease. SUMMARY: The current review outlines the clinical use of RVFWS, and its integration with other commonly used echocardiographic measurements to more accurately assess RV function, cause and prognosis to guide and improve patient care decision making.

Three-dimensional thoracic aorta principal strain analysis from routine ECG-gated computerized tomography: feasibility in patients undergoing transcatheter aortic valve replacement.

BACKGROUND: Functional impairment of the aorta is a recognized complication of aortic and aortic valve disease. Aortic strain measurement provides effective quantification of mechanical aortic function, and 3-dimenional (3D) approaches may be desirable for serial evaluation. Computerized tomographic angiography (CTA) is routinely performed for various clinical indications, and offers the unique potential to study 3D aortic deformation. We sought to investigate the feasibility of performing 3D aortic strain analysis in a candidate population of patients undergoing transcatheter aortic valve replacement (TAVR). METHODS: Twenty-one patients with severe aortic valve stenosis (AS) referred for TAVR underwent ECG-gated CTA and echocardiography. CTA images were analyzed using a 3D feature-tracking based technique to construct a dynamic aortic mesh model to perform peak principal strain amplitude (PPSA) analysis. Segmental strain values were correlated against clinical, hemodynamic and echocardiographic variables. Reproducibility analysis was performed. RESULTS: The mean patient age was 81±6 years. Mean left ventricular ejection fraction was 52±14%, aortic valve area (AVA) 0.6±0.3 cm2 and mean AS pressure gradient (MG) 44±11 mmHg. CTA-based 3D PPSA analysis was feasible in all subjects. Mean PPSA values for the global thoracic aorta, ascending aorta, aortic arch and descending aorta segments were 6.5±3.0, 10.2±6.0, 6.1±2.9 and 3.3±1.7%, respectively. 3D PSSA values demonstrated significantly more impairment with measures of worsening AS severity, including AVA and MG for the global thoracic aorta and ascending segment (p<0.001 for all). 3D PSSA was independently associated with AVA by multivariable modelling. Coefficients of variation for intra- and inter-observer variability were 5.8 and 7.2%, respectively. CONCLUSIONS: Three-dimensional aortic PPSA analysis is clinically feasible from routine ECG-gated CTA. Appropriate reductions in PSSA were identified with increasing AS hemodynamic severity. Expanded study of 3D aortic PSSA for patients with various forms of aortic disease is warranted.