Stabilization of Rapidly Progressive Cardiac Allograft Vasculopathy Using mTOR Inhibition After Heart Transplantation.

BACKGROUND: Inhibition of the mammalian target of rapamycin (mTor) pathway after heart transplantation has been associated with reduced progression of coronary allograft vasculopathy (CAV). The application of low-dose mTOR inhibition in the setting of modern immunosuppression, including tacrolimus, remains an area of limited exploration. METHODS: This retrospective study included patients who received heart transplantation between January 2009 and January 2019 and had baseline, 1-year and 2-3-year coronary angiography with intravascular ultrasound (IVUS). Intimal thickness in 5 segments along the left anterior descending artery was compared across imaging time points in patients who were transitioned to low-dose mTOR inhibitor (sirolimus) vs standard treatment with mycophenolate on a background of tacrolimus. Long-term adverse cardiovascular outcomes (revascularization, severe CAV, retransplant, and cardiovascular death) were also assessed. RESULTS: Among 216 patients (mean age 51.5 ± 11.9 years, 77.8% men, 80.1% white), 81 individuals (37.5%) were switched to mTOR inhibition. mTOR inhibition was associated with a reduction in intimal thickness by 0.05 mm (95% CI 0.02-0.07; P < 0.001). This reduction was driven by patients who met the criteria for rapidly progressive CAV 1-year post-transplant (0.12 mm; P = 0.016 for interaction). After a median follow-up of 8.6 (IQR 6.6-11) years, 40 patients had major adverse cardiovascular outcomes. The use of mTOR inhibitors was not significantly associated with cardiovascular outcomes (P = 0.669). CONCLUSION: Transitioning patients after heart transplantation to an immunosuppression regimen composed of low-dose mTOR inhibition and tacrolimus was associated with a lack of progression of CAV, particularly in those with rapidly progressive CAV at 1 year, but not with long-term cardiovascular outcomes.

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.

Accurate and efficient rapid acquisition early post-injection stress-first CZT SPECT myocardial perfusion imaging with tetrofosmin and attenuation correction.

INTRODUCTION: Myocardial perfusion imaging (MPI) protocols have not changed significantly despite advances in instrumentation and software. We compared an early post-injection, stress-first SPECT protocol to standard delayed imaging. METHODS: 95 patients referred for SPECT MPI were imaged upright and supine on a Spectrum Dynamics D-SPECT CZT system with CT attenuation correction. Patients received injection of 99mTc tetrofosmin at peak of regadenoson stress and were imaged. Early post-stress (mean 17 ± 2 minutes) and Standard 1-h delay (mean 61 ± 13 min). Three blinded readers evaluated images for overall interpretation, perceived need for rest imaging, image quality, and reader confidence. Laboratory efficiency was also evaluated. RESULTS: Blinded readers had the same response for the need for rest in 77.9% of studies. Studies also had the same interpretation in 89.5% of studies. Reader confidence was high (86.0% (Early) and 90.3% (Standard p = 0.52. Image quality was good or excellent in 87.4% Early vs 96.8% Standard (p = 0.09). Time between patient check-in and end of stress imaging was 104 ± (Standard) to 60 ± 18 minutes (Early) (p < 0.001). CONCLUSION: Early post-injection stress-only imaging using CZT SPECT/CT appears promising with Tc-99m tetrofosmin with similar image quality, reader confidence, diagnosis, and need for a rest scan.

Hot spot imaging in cardiovascular diseases: an information statement from SNMMI, ASNC, and EANM.

This information statement from the Society of Nuclear Medicine and Molecular Imaging, American Society of Nuclear Cardiology, and European Association of Nuclear Medicine describes the performance, interpretation, and reporting of hot spot imaging in nuclear cardiology. The field of nuclear cardiology has historically focused on cold spot imaging for the interpretation of myocardial ischemia and infarction. Hot spot imaging has been an important part of nuclear medicine, particularly for oncology or infection indications, and the use of hot spot imaging in nuclear cardiology continues to expand. This document focuses on image acquisition and processing, methods of quantification, indications, protocols, and reporting of hot spot imaging. Indications discussed include myocardial viability, myocardial inflammation, device or valve infection, large vessel vasculitis, valve calcification and vulnerable plaques, and cardiac amyloidosis. This document contextualizes the foundations of image quantification and highlights reporting in each indication for the cardiac nuclear imager.

Outpatient Management of Guideline-Directed Medical Therapy for Heart Failure Using Telehealth: A Comparison of In-Office, Video, and Telephone Visits.

BACKGROUND: There are limited data regarding the management of guideline-directed medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF) with virtual visits in comparison with in-office visits. We sought to compare the changes in GDMT (angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, angiotensin receptor neprilysin inhibitors, mineralocorticoid receptor antagonists, and sodium glucose cotransporter-2 inhibitors) and loop diuretics across visit types. METHODS AND RESULTS: This study included 13,481 outpatient visits performed for 5439 unique patients with HFrEF between March 16, 2020, and March 15, 2021. The rates of initiation and discontinuation of GDMT were documented, and multivariable logistic regression was performed to test associations with outcomes between modes of visit. The rates of medication initiation were higher in office (11.7%) compared with video (9.6%) or telephone (7.2%) visits. In multivariable adjusted analysis, the initiation of at least 1 GDMT class was similar between in-office visits and video visits (adjusted odds ratio [OR] 0.97, 95% confidence interval [CI] 0.82-1.14, P = .703). Telephone visits were associated with less frequent initiation of at least 1 class of GDMT in comparison with in-office visits (adjusted OR 0.64, 95% CI 0.55-0.75; P < .001) and video visits (adjusted OR 0.67, 95% CI 0.55-0.81, P < .001). Despite similar rates of baseline loop diuretic use, patients seen with both video visits (adjusted OR 0.70, 95% CI 0.52-0.94, P = .018) and telephone visits (adjusted OR 0.64, 95% CI 0.49-0.83, P < .001) were less likely to have a loop diuretic initiated when compared with in-office visits. CONCLUSIONS: The initiation of GDMT for HFrEF was similar between in-office and video visits and lower with telephone visits, whereas the initiation of a loop diuretic was less frequent in both types of virtual visits. These data suggest that video streaming capabilities should be encouraged for virtual visits.

Comprehensive approach to cardiac amyloidosis care: considerations in starting an amyloidosis program.

Amyloidosis is a multisystem disease which continues to present in later stages due to delayed diagnosis. Once the disease is identified, the coordination of ongoing care and treatment becomes complex and often involves multiple specialists. As knowledge of the disease grows, healthcare providers within institutions have organized to create comprehensive amyloidosis programs to better serve patients in the region. In this review, we present considerations in starting a cardiac amyloidosis program from two institutions that have recently started such programs. Identification of multidisciplinary stakeholders, development of overarching program goals, creation of institutional buy-in, and emphasis on program growth and development are tenets of a successful program. The creation and growth of an amyloidosis program has the potential to raise awareness for the disease and benefit patients and institutions alike.

Challenges and the innovations in the care of advanced heart failure patients during COVID-19.

The COVID-19 pandemic underscored our healthcare system's unpreparedness to manage an unprecedented pandemic. Heart failure (HF) physicians from 14 different academic and private practice centers share their systems' challenges and innovations to care for patients with HF, heart transplantation, and patients on LVAD support during the COVID-19 pandemic. We discuss measures implemented to alleviate the fear in seeking care, ensure continued optimization of guideline directed medical therapy (GDMT), manage the heart transplant waiting list, continue essential outpatient monitoring of anticoagulation in LVAD patients and surveillance testing post-heart transplant, and prevent physician burnout. This collaborative work can build a foundation for better preparation in the face of future challenges.

The effect of recipient BMI on waitlist and post-transplant outcomes after the 2018 heart transplant allocation policy change.

OBJECTIVE: The effects of recipient body mass index (BMI) on waitlist strategies, waitlist outcomes, and post-transplant outcomes among adult patients listed for heart transplantation under the updated 2018 allocation system have not been well characterized. METHODS: The United Network of Organ Sharing data set between October 2015 and March 2021 was analyzed, and patients were grouped based on recipient BMI and whether listing occurred in the old (pre-October 2018) or new allocation system. RESULTS: Listing strategies differed by BMI group, but trends of increased use of temporary mechanical support and decreased use of durable support remained among all BMI groups, except those with BMI > 35 kg/m2 . Waitlist outcomes improved among all BMI cohorts in the new allocation system, including among patients with BMI 30-34.9 and >35 kg/m2 , although patients with higher BMIs continued to have longer waitlist times. Post-transplant outcomes in the new allocation system are worse for patients with BMI > 30 kg/m2  (hazard ratio: 1.47; confidence interval: 1.19-1.82; p < .001). CONCLUSIONS: The 2018 change to the heart transplant allocation system was associated with similar changes in the use of mechanical support for listing strategy across BMI ranges, except in the most obese, and improved waitlist outcomes across all BMI ranges. Post-transplant outcomes in the new allocation system are worse for patients with BMI > 30 kg/m2  compared to patients with BMI < 30 kg/m2 . These findings have important clinical implications for our understanding of the ongoing influence of BMI on waitlist courses and post-transplant outcomes among patients listed for heart transplantation.

Cost-Effectiveness of Tafamidis Therapy for Transthyretin Amyloid Cardiomyopathy.

BACKGROUND: In patients with transthyretin amyloid cardiomyopathy, tafamidis reduces all-cause mortality and cardiovascular hospitalizations and slows decline in quality of life compared with placebo. In May 2019, tafamidis received expedited approval from the US Food and Drug Administration as a breakthrough drug for a rare disease. However, at $225 000 per year, it is the most expensive cardiovascular drug ever launched in the United States, and its long-term cost-effectiveness and budget impact are uncertain. We therefore aimed to estimate the cost-effectiveness of tafamidis and its potential effect on US health care spending. METHODS: We developed a Markov model of patients with wild-type or variant transthyretin amyloid cardiomyopathy and heart failure (mean age, 74.5 years) using inputs from the ATTR-ACT trial (Transthyretin Amyloidosis Cardiomyopathy Clinical Trial), published literature, US Food and Drug Administration review documents, healthcare claims, and national survey data. We compared no disease-specific treatment ("usual care") with tafamidis therapy. The model reproduced 30-month survival, quality of life, and cardiovascular hospitalization rates observed in ATTR-ACT; future projections used a parametric survival model in the control arm, with constant hazards reduction in the tafamidis arm. We discounted future costs and quality-adjusted life-years by 3% annually and examined key parameter uncertainty using deterministic and probabilistic sensitivity analyses. The main outcomes were lifetime incremental cost-effectiveness ratio and annual budget impact, assessed from the US healthcare sector perspective. This study was independent of the ATTR-ACT trial sponsor. RESULTS: Compared with usual care, tafamidis was projected to add 1.29 (95% uncertainty interval, 0.47-1.75) quality-adjusted life-years at an incremental cost of $1 135 000 (872 000-1 377 000), resulting in an incremental cost-effectiveness ratio of $880 000 (697 000-1 564 000) per quality-adjusted life-year gained. Assuming a threshold of $100 000 per quality-adjusted life-year gained and current drug price, tafamidis was cost-effective in 0% of 10 000 probabilistic simulations. A 92.6% price reduction from $225 000 to $16 563 would be necessary to make tafamidis cost-effective at $100 000/quality-adjusted life-year. Results were sensitive to assumptions related to long-term effectiveness of tafamidis. Treating all eligible patients with transthyretin amyloid cardiomyopathy in the United States with tafamidis (n=120 000) was estimated to increase annual healthcare spending by $32.3 billion. CONCLUSIONS: Treatment with tafamidis is projected to produce substantial clinical benefit but would greatly exceed conventional cost-effectiveness thresholds at the current US list price. On the basis of recent US experience with high-cost cardiovascular medications, access to and uptake of this effective therapy may be limited unless there is a large reduction in drug costs.

Influence of Donor Transmitted and Rapidly Progressive Coronary Vascular Disease on Long-Term Outcomes After Heart Transplantation: A Contemporary Intravascular Ultrasound Analysis.

BACKGROUND: Donor-transmitted atherosclerosis (DTA) and rapidly progressive cardiac allograft vasculopathy (CAV) at 1 year are intravascular ultrasound (IVUS)-derived measures shown to predict adverse cardiovascular outcomes in the setting of early generation immunosuppressive agents. Given the paucity of data on the prognostic value of IVUS-derived measurements in the current era, we sought to explore their association with adverse outcomes after heart transplantation. METHODS AND RESULTS: This is a retrospective cohort analysis of patients who underwent heart transplantation at our center between January 2009 and June 2016 with baseline and 1-year IVUS. Five IVUS sections were prospectively analyzed for intimal thickness and lumen area. DTA was defined as maximum intimal thickness of 0.5 mm or greater at baseline, and rapidly progressive CAV as an increase in maximum intimal thickness by 0.5 mm or more at 1 year. Our primary analysis assessed the relationship of IVUS and other clinical data on a composite outcome: coronary intervention, CAV stage 2 or 3 (defined by the International Society for Heart and Lung Transplantation 2010 nomenclature), or cardiovascular death. Among 249 patients (mean age 51.0 ± 12.2 years and 74.3% male) included in the analysis, DTA was detected in 118 patients (51.4%). Over a median follow-up of 6.1 years (interquartile range 4.2-8.0 years), 45 patients met the primary end point (23 percutaneous coronary intervention, 11 CAV 2 or 3, and 11 cardiovascular deaths as first event). DTA and rapidly progressive CAV were not associated with the primary end point, all-cause mortality, or retransplantation. In an additional analysis including post-transplant events, incident rejection was strongly associated with poor outcomes, although cytomegalovirus infection was not. CONCLUSIONS: In this contemporary cohort, IVUS-derived DTA and rapidly progressive CAV were not associated with medium- to long-term adverse events after heart transplantation.

PCSK9 Inhibitors in Heart Transplant Patients: Safety, Efficacy, and Angiographic Correlates.

BACKGROUND: Statins are recommended in heart transplant patients, but are sometimes poorly tolerated. Alternative agents are often considered including proprotein convertase subtilisin/kexin type-9 inhibitors (PCSK9i). We sought to investigate the use of PCSK9i after heart transplantation. METHODS AND RESULTS: We identified patients who received a heart transplant from 1999 to 2019 and were started on PCSK9i at our institution. Clinical, laboratory, and coronary angiography with intravascular ultrasound results were compared. Among 65 patients initiated on PCSK9i (48 for statin intolerance and 17 for refractory hyperlipidemia), the median time from transplant was 5.5 years (interquartile range [IQR], 2.8-9.9 years) with a median PCSK9 treatment duration of 1.6 years (IQR, 0.8-3.2 years) and 80% still on treatment. Evolocumab was used in 73.8%, alirocumab in 12.3%, and both in 13.8% owing to insurance coverage. All patients required prior authorization; initial denial occurred in 18.5% and 32.3% had denials in subsequent years. The median low-density lipoprotein cholesterol decreased from 130 mg/dL (IQR, 102-148 mg/dL) to 55 mg/dL (IQR, 35-74 mg/dL) after starting PCSK9i (P < .001), with 72% of patients achieving a low-density lipoprotein cholesterol of <70 mg/dL after treatment. There were also significant reductions of total cholesterol, non-high-density lipoprotein cholesterol, total/high-density lipoprotein cholesterol ratio, and triglycerides, with a modest increase in high-density lipoprotein cholesterol. These changes were durable at latest follow-up. In 33 patients with serial coronary angiography and intravascular ultrasound, PCSK9i were associated with stable coronary plaque thickness and lumen area. CONCLUSIONS: Among heart transplant recipients, PCSK9i are effective in lowering cholesterol levels and stabilizing coronary intimal hyperplasia with minimal side effects. Despite favorable effects, access and affordability remain a challenge.

Single-center utilization of donor-derived cell-free DNA testing in the management of heart transplant patients.

BACKGROUND: Gene expression profiling (GEP) and donor-derived cell-free DNA (dd-cfDNA) are useful in acute rejection (AR) surveillance in orthotopic heart transplant (OHT) patients. We report a single-center experience of combined GEP and dd-cfDNA testing for AR surveillance. METHODS: GEP and dd-cfDNA are tested together starting at 2 months post-OHT. After 6 months, combined testing was obtained before scheduled endomyocardial biopsy (EMB), and EMB was canceled with a negative dd-cfDNA. This approach was compared to using a GEP-only approach, where EMB was canceled with a negative GEP. We evaluated for frequency of EMB cancellation with dd-cfDNA usage. RESULTS: A total of 153 OHT patients over a 13-month period underwent 495 combined GEP/dd-cfDNA tests. 82.2% of dd-cfDNA tests were below threshold. Above threshold results identified high-risk patients who developed AR. 378 combined tests ≥6 months post-OHT resulted in cancellation of 83.9% EMBs as opposed to 71.2% with GEP surveillance alone. There were 2 acute cellular and 2 antibody-mediated rejection episodes, and no significant AR ≥6 months. CONCLUSION: Routine dd-cfDNA testing alongside GEP testing yielded a significant reduction in EMB volume by re-classifying GEP (+) patients into a lower risk group, without reduction in AR detection. The addition of dd-cfDNA identified patients at higher risk for AR.

Stress myocardial perfusion imaging in patients presenting with syncope: Comparison of PET vs. SPECT.

BACKGROUND: The role of myocardial perfusion imaging (MPI) in patients with suspected coronary artery disease (CAD) presenting with syncope is controversial. We aimed to determine diagnostic yield of MPI for evaluation of syncope in patients without known CAD, as a function of pre-test patient risk and test modality (PET vs SPECT). METHODS: Between 1/2010 and 12/2016, 1324 consecutive patients presenting with syncope without known CAD underwent MPI with PET (n = 640) or SPECT (n = 684). Rates of abnormal MPI (summed difference score (SDS) > 2 or left ventricular ejection fraction (LVEF) reserve ≤ 0 for PET and SDS > 2 or post-stress LVEF ≤ 45% for SPECT) were determined among patients stratified by pre-test risk. In patients who were referred for coronary angiography, diagnostic yield of obstructive CAD was calculated in the overall cohort as well as in a propensity-matched cohort compared to patients without syncope. RESULTS: Abnormal MPI was noted in 36.5% (201/551) of patients who had PET compared with 13.0% (87/671) who had SPECT (P < 0.001), which is largely related to higher comorbidity burden and greater pre-test CAD risk in the PET population. Among patients who had an abnormal MPI, 8.5% (47/551) with PET and 0.7% (5/671) with SPECT were found to have obstructive CAD if referred for coronary angiography. Patients at intermediate-high pre-test risk had a higher proportion of abnormal MPIs and obstructive CAD as compared to those at low risk in both the PET and SPECT cohorts. The rate of abnormal testing and diagnostic yield of PET MPI was similar and proportionate to pre-test likelihood among matched patients with and without syncope. CONCLUSIONS: Among patients referred for PET MPI with syncope at an intermediate-high pre-test CAD risk, 1 in 3 had an abnormal MPI and 1 in 10 had obstructive CAD. The value of MPI was related to pre-test risk as opposed to the presence of syncope, and MPI testing with PET or SPECT in the low-risk population was low value.

Myocardial blood flow reserve assessed by positron emission tomography myocardial perfusion imaging identifies patients with a survival benefit from early revascularization.

AIMS: Positron emission tomography (PET) myocardial perfusion imaging (MPI) can non-invasively measure myocardial blood flow reserve (MBFR). We aimed to examine whether MBFR identifies patients with a survival benefit after revascularization, helping to guide post-test management. METHODS AND RESULTS: We examined all-cause mortality in 12 594 consecutive patients undergoing Rb82 rest/stress PET MPI from January 2010 to December 2016, after excluding those with cardiomyopathy, prior coronary artery bypass surgery (CABG), and missing MBFR. Myocardial blood flow reserve was calculated as the ratio of stress to rest absolute myocardial blood flow. A Cox model adjusted for patient and test characteristics, early revascularization (percutaneous coronary intervention or CABG ≤90 days of MPI), and the interaction between MBFR and early revascularization was developed to identify predictors of all-cause mortality. After a median follow-up of 3.2 years, 897 patients (7.1%) underwent early revascularization and 1699 patients (13.5%) died. Ischaemia was present in 4051 (32.3%) patients, with 1413 (11.2%) having ≥10% ischaemia. Mean MBFR was 2.0 ± 1.3, with MBFR <1.8 in 4836 (38.5%). After multivariable adjustment, every 0.1 unit decrease in MBFR was associated with 9% greater hazard of all-cause death (hazard ratio 1.09, 95% confidence interval 1.08-1.10; P < 0.001). There was a significant interaction between MBFR and early revascularization (P < 0.001); such that patients with MBFR ≤1.8 had a survival benefit with early revascularization, regardless of type of revascularization or level of ischaemia. CONCLUSION: Myocardial blood flow reserve on PET MPI is associated with all-cause mortality and can identify patients who receive a survival benefit with early revascularization compared to medical therapy. This may be used to guide revascularization, and prospective validation is needed.

Technetium pyrophosphate nuclear scintigraphy for cardiac amyloidosis: Imaging at 1 vs 3 hours and planar vs SPECT/CT.

BACKGROUND: Multi-societal consensus recommendations endorse both planar and single photon emission tomographic (SPECT) image acquisitions for the evaluation of cardiac amyloidosis. However, the correlation between planar and SPECT findings and the optimal timing of image acquisitions remain uncertain. METHODS: This is an analysis of 109 consecutive patients who underwent technetium pyrophosphate nuclear scintigraphy for the evaluation of cardiac amyloidosis. Patients were imaged at 1 and 3 hours after radiotracer injection using both planar and SPECT/CT, and the correlations between imaging protocols were compared. RESULTS: In the overall cohort (median age 77 years, 75% male), 33 patients had radiotracer localized to the myocardium on SPECT/CT images. There was strong correlation between 1- and 3-hour planar heart-to-contralateral lung ratios (mean difference 0.07, r = 0.94). However, there was discordance between planar image interpretation (based upon semiquantitative score and H/CL ratio) and myocardial localization of radiotracer on SPECT/CT in 17 patients (16%). The pattern of SPECT/CT uptake was identical at 1 and 3 hours in all cases (32 diffuse, 1 focal). CONCLUSION: These data support the recommendation that SPECT/CT should be obtained in addition to planar images when performing nuclear scintigraphy for the detection of cardiac amyloidosis. A 1-hour planar and SPECT/CT protocol appears optimal.

Evolution of Diagnostic and Treatment Patterns of Cardiac Sarcoidosis.

Cardiac sarcoidosis (CS) may impart substantial morbidity and mortality, and novel imaging modalities are now available to aid in early diagnosis of this clinically silent disease. A better understanding of the clinical experience with CS is important. Twenty-eight patients were diagnosed with the aid of multimodality imaging techniques and were treated by a multidisciplinary team. Demographics, symptomatology, imaging, and therapeutic interventions were compiled from our referral center. In patients with CS, nuclear and MR techniques were often the first studies performed. Echocardiographic findings differed widely. Immunosuppressive therapy and cardiac devices were frequently used. Importantly, isolated CS was not an infrequent finding.

Non-cardiac uptake of technetium-99m pyrophosphate in transthyretin cardiac amyloidosis.

BACKGROUND: Technetium-based bone scintigraphy is rapidly becoming the most common non-invasive imaging tool in the diagnosis of Transthyretin cardiac amyloidosis (ATTR). Skeletal muscle uptake has been described with technetium-99m-3,3-diphosphono-1,2-propanodicarboxylic acid (TcDPD), and may account for masking of bony uptake. We sought to investigate skeletal muscle uptake of technetium-99m-pyrophosphate (TcPYP) in patients with ATTR. METHODS AND RESULTS: This was a retrospective analysis of 57 patients diagnosed with ATTR who underwent TcPYP scintigraphy. Cardiac uptake was assessed on whole-body planar imaging using a semiquantitative scale (grades 0 to 3) and on single-photon emission computed tomography (SPECT) with CT attenuation correction using total myocardial counts per voxel after a 3-hour incubation. Skeletal muscle (psoas and biceps), vertebral body, LV myocardium, and blood pool mean counts were calculated. In the cohort (age 78 ± 9 years, 77% male, and 30% hereditary ATTR), there was no visualized tracer uptake in skeletal muscle or soft tissue on qualitative SPECT assessment. Total and blood pool-corrected uptake in the muscle groups were significantly less than myocardium and bone (P < 0.001). Blood pool-corrected muscle uptake was not associated with semiquantitative grade 3 vs 2 uptake (psoas P = 0.66, biceps P = 0.13) or presence of hereditary ATTR (psoas P = 0.43, biceps P = 0.69). As bony uptake decreased, there was no corresponding increase in skeletal muscle uptake. CONCLUSIONS: In patients with ATTR cardiac amyloidosis, skeletal muscle uptake of TcPYP is minimal when assessed by qualitative and quantitative metrics, and is not significantly different in patients with grade 2 vs 3 semiquantitative uptake. The properties of this tracer may be different than TcDPD with respect to non-cardiac uptake.

Implantable cardioverter-defibrillators and survival in advanced heart failure patients with continuous-flow left ventricular assist devices: a systematic review and meta-analysis.

AIMS: Implantable cardioverter-defibrillators (ICDs) implantation in heart failure (HF) patients with reduced ejection fraction improves survival by reducing mortality secondary to arrhythmic events. Whether advanced HF patients treated with continuous-flow left ventricular assist devices (CF-LVADs) derive similar benefit is controversial. METHODS AND RESULTS: We searched PubMed, Cochrane Central Register of Controlled Trials, Embase, and Scopus from inception through November 2018 for studies examining the association between ICD implantation and all-cause mortality in patients with advanced HF and CF-LVADs. Analyses were performed using a random-effects model. Hazard ratios (HRs) were calculated with 95% confidence intervals (CIs). Heterogeneity and publication bias were formally assessed, using I2 and funnel plots, respectively. Eight observational studies with a total of 6416 patients (ICD group = 3450, no ICD group = 2966) met inclusion criteria. The majority of patients (84.6%) came from the two largest observational studies. There was no difference in mortality in the ICD and no ICD groups (HR 0.96, 95% CI 0.73-1.27, P = 0.79, I2 = 42%), and ICD implantation post-CF-LVAD was not associated with an improvement in mortality (HR 0.87, 95% CI 0.48-1.57, P = 0.64, I2 = 0%). Additionally, there was no significant difference in the likelihood of transplantation (HR 1.10, 95% CI 0.93-1.30, P = 0.28, I2 = 26%) or non-mortality adverse events between the two groups. CONCLUSION: Implantable cardioverter-defibrillator use was not associated with improved survival in advanced HF patients with CF-LVADs. These findings underscore the need to formally study the efficacy of ICDs in this population in a dedicated randomized controlled study.