The association with organ procurement techniques and early cardiac transplant outcomes using cardiac MRI.

BACKGROUND: Heart transplantation (HT) has historically been limited by organ availability. Use of donation after circulatory death (DCD) donors addresses this limitation by utilizing previously unused hearts through use of the Organ Care System (OCS). OBJECTIVES: This study aimed to determine the impact of procurement and transportation method on allograft structure and function using early post-transplant cardiac magnetic resonance imaging (MRI). METHODS: Patients who underwent HT at our institution from February 1, 2020, through April 30, 2021 who underwent cardiac MRI imaging <60 days from transplant were included. Recipient and donor characteristics, clinical outcomes, and MRI findings were compared between those who underwent DCD transplantation using the OCS device (DCD-OCS), brain dead donation (DBD) using the OCS device (DBD-OCS), and DBD transported via cold storage (DBD-cold storage) using one-way analysis of variance. RESULTS: A total of 85 patients underwent HT with a cardiac MRI during the study period. Thirty-one (36%) patients received a DCD organ, 16 (19%) received a DBD-OCS organ and 38 (45%) received a DBD-cold storage organ. Rates of primary graft dysfunction (PGD) were significantly higher in DCD transplants (19.5% DCD vs. .0% DBD-OCS and 5.3% DBD-cold storage; p < .050 across three groups), but with no differences in mortality or rejection. There were no differences in cardiac MRI findings between the three transplant types, including presence of gadolinium hyperenhancement after transplant (all p > .050). CONCLUSIONS: We observed no differences in early cardiac MRI findings between patients that received DCD and DBD-OCS heart transplants compared with those receiving DBD-cold storage transplants.

Trends in cardiovascular medicine: Update on cardiac transplantation.

Advanced heart failure affects more than 250,000 people in the United States alone and is associated with high risk of morbidity and mortality. Cardiac transplantation provides a cure for patients with advanced disease but has historically been limited by donor availability. Recent changes in the allocation system as well as advances in donor selection, procurement and desensitization protocols have served to widen the donor pool and increase the availability of cardiac transplantation for those in need. This review provides an update on recent advances in cardiac transplantation.

One Small Step for a Patient, One Giant Leap for Orthostatic Hypotension.

A 52-year-old man with ischemic cardiomyopathy presented with progressive, severe orthostatic hypotension refractory to medical therapy. Standard abdominal and leg compression devices were used without success. A novel, inflatable abdominal compression device was created that alleviated the patient's symptoms and maintained his blood pressure.

Neighborhood Socioeconomic Disadvantage and Hospitalized Heart Failure Outcomes in the American Heart Association Get With The Guidelines-Heart Failure Registry.

BACKGROUND: Neighborhood socioeconomic status (SES) is associated with worse health outcomes, yet its relationship with in-hospital heart failure (HF) outcomes and quality metrics are underexplored. We examined the association between socioeconomic neighborhood disadvantage and in-hospital HF outcomes for patients from diverse neighborhoods in the Get With The Guidelines-Heart Failure registry. METHODS: SES-disadvantage scores were derived from geocoded US census data using a validated algorithm, which incorporated household income, home value, rent, education, and employment. We examined the association between SES-disadvantage quintiles with all-cause in-hospital mortality, adjusting for demographics and comorbidities. RESULTS: Of 593 053 patients hospitalized for HF between 2017 and 2020, 321 314 (54%) had residential ZIP Codes recorded. Patients from the most compared with least disadvantaged neighborhoods were younger (mean age 67 versus 76 years), more often Black (42% versus 9%) or Hispanic (14% versus 5%), and had higher comorbidity burden. Demographic-adjusted length of stay increased by ≈1.5 hours with each increment in worsening SES-disadvantage quintiles. Adjusted-mortality odds ratios increased with worsening SES-disadvantage quintiles (Ptrend=0.003), and was 28% higher (adjusted OR=1.28 [1.12-1.48]) for the most compared with least disadvantaged neighborhood groups. CONCLUSIONS: Patients hospitalized for HF from disadvantaged neighborhoods were younger and more often Black or Hispanic. SES disadvantage was independently associated with higher in-hospital mortality. Further research is needed to characterize care delivery patterns in disadvantaged neighborhoods and to address social determinants of health among patients hospitalized for HF. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02693509.

Prevalence and Phenotypic Burden of Monogenic Arrhythmias Using Integration of Electronic Health Records With Genetics.

BACKGROUND: Inherited primary arrhythmia syndromes and arrhythmogenic cardiomyopathies can lead to sudden cardiac arrest in otherwise healthy individuals. The burden and expression of these diseases in a real-world, well-phenotyped cardiovascular population is not well understood. METHODS: Whole exome sequencing was performed on 8574 individuals from the CATHGEN cohort (Catheterization Genetics). Variants in 55 arrhythmia-related genes (associated with 8 disorders) were identified and assessed for pathogenicity based on American College of Genetics and Genomics/Association for Molecular Pathology criteria. Individuals carrying pathogenic/likely pathogenic (P/LP) variants were grouped by arrhythmogenic disorder and matched 1:5 to noncarrier controls based on age, sex, and genetic ancestry. Long-term phenotypic data were annotated through deep electronic health record review. RESULTS: Fifty-eight P/LP variants were found in 79 individuals in 12 genes associated with 5 arrhythmogenic disorders (arrhythmogenic right ventricular cardiomyopathy, Brugada syndrome, hypertrophic cardiomyopathy, LMNA-related cardiomyopathy, and long QT syndrome). The penetrance of these P/LP variants in this cardiovascular cohort was 33%, 0%, 28%, 83%, and 4%, respectively. Carriers of P/LP variants associated with arrhythmogenic disorders showed significant differences in ECG, imaging, and clinical phenotypes compared with noncarriers, but displayed no difference in survival. Carriers of novel truncating variants in FLNC, MYBPC3, and MYH7 also developed relevant arrhythmogenic cardiomyopathy phenotypes. CONCLUSIONS: In a real-world cardiovascular cohort, P/LP variants in arrhythmia-related genes were relatively common (1:108 prevalence) and most penetrant in LMNA. While hypertrophic cardiomyopathy P/LP variant carriers showed significant differences in clinical outcomes compared with noncarriers, carriers of P/LP variants associated with other arrhythmogenic disorders displayed only ECG differences.

Transplanting thoracic COVID-19 positive donors: An institutional protocol and report of the first 14 cases.

We present our institution's protocol for evaluating and transplanting thoracic organs from COVID-19 positive donors and report the outcomes to date. Hearts from donors testing positive for COVID-19 on any test were eligible for transplantation at our institution provided the donor exhibited no evidence of hypercoagulability or COVID-19 induced hyperinflammatory state during terminal hospitalization. Lungs were eligible if the donor first tested PCR positive on nasopharyngeal swab (NPS) for COVID-19 > 20 days prior to procurement and had a negative lower respiratory tract specimen. We performed 14 thoracic transplants in 13 recipients using organs from COVID-19 positive donors. None of the recipients or healthcare members acquired COVID-19. No recipients suffered unexpected acute rejection. Patient survival is 92% to date, with graft survival 93%. The use of hearts from COVID-19 positive donors may be safe and effective. Transplantation of lungs is unresolved but may be cautiously pursued under the restricted circumstances.

Sleep Breathing Disorders in Heart Failure.

Sleep-disordered breathing (SDB), including obstructive sleep apnea, central sleep apnea (CSA), and Cheyne-Stokes respiration, is common in patients with heart failure (HF) and associated with lower left ventricular ejection fraction (EF), increased arrhythmia burden, and increased mortality. Continuous positive airway pressure therapy improves short-term and long-term outcomes in HF patients. Adaptive servoventilation (ASV) therapy in patients with low-EF HF with predominant CSA is not recommended. Ongoing trials are evaluating whether ASV will have a role in SDB treatment. Phrenic nerve stimulation is an emerging treatment option that has shown promising outcomes. All HF patients should be screened for SDB.

Transthyretin V142I Genetic Variant and Cardiac Remodeling, Injury, and Heart Failure Risk in Black Adults.

OBJECTIVES: This study evaluated the association of transthyretin (TTR) gene variant, in which isoleucine substitutes for valine at position 122 (V142I), with cardiac structure, function, and heart failure (HF) risk among middle-aged Black adults. BACKGROUND: The valine-to-isoleucine substitution in the TTR protein is prevalent in Black individuals and causes cardiac amyloidosis. METHODS: Jackson Heart Study participants without HF at baseline who had available data on the TTR V142I variant were included. The association of the TTR V142I variant with baseline echocardiographic parameters and repeated measures of high-sensitivity cardiac troponin-I (hs-cTnI) was assessed using adjusted linear regression models and linear mixed models, respectively. Adjusted Cox models, restricted mean survival time analysis, and Anderson-Gill models were constructed to determine the association of TTR V142I variant with the risk of incident HF, survival free of HF, and total HF hospitalizations. RESULTS: A total of 119 of 2,960 participants (4%) were heterozygous carriers of the TTR V142I variant. The TTR V142I variant was not associated with measures of cardiac parameters at baseline but was associated with a greater increase in high-sensitivity troponin I (hs-TnI) levels over time. In adjusted Cox models, TTR V142I variant carriers had significantly higher risk of incident HF (HR: 1.80; 95% CI: 1.07-3.05; P = 0.03), lower survival free of HF (mean difference: 4.0 year; 95% CI: 0.6-6.2 years); P = 0.02), and higher risk of overall HF hospitalizations (HR: 2.12; 95% CI: 1.23-3.63; P = 0.007). CONCLUSIONS: The TTR V142I variant in middle-aged Black adults is not associated with adverse cardiac remodeling but was associated with a significantly higher burden of chronic myocardial injury, and greater risk of incident HF and overall HF hospitalizations.

Innovations in Heart Transplantation: A Review.

Advanced heart failure affects tens of thousands of people in the United States alone with high morbidity and mortality. Cardiac transplantation offers the best treatment strategy, but has been limited historically by donor availability. Recently, there have been significant advances in organ allocation, donor-recipient matching, organ preservation, and expansion of the donor pool. The current heart allocation system prioritizes the sickest patients to minimize waitlist mortality. Advances in donor organ selection, including predicted heart mass calculations and more sophisticated antibody detection methods for allosensitized patients, offer more effective matching of donors and recipients. Innovations in organ preservation such as with organ preservation systems have widened the donor pool geographically. The use of donors with hepatitis C is possible with the advent of effective direct-acting antiviral agents to cure donor-transmitted hepatitis C. Finally, further expansion of the donor pool is occurring with the use of higher risk donors with advanced age, medical comorbidities, and left ventricular dysfunction and advances in donation after circulatory death. This review provides an update on the new technologies and transplantation strategies that serve to widen the donor pool and more effectively match donors and recipients so that heart transplant candidates may derive the best outcomes from heart transplantation.

A Case for Re-Gifting.

Many patients die while waiting for a heart transplant. Therefore, it is vital that all suitable organs are used for transplantation. We present a case of an allograft that was transplanted twice and outline considerations regarding tissue typing, the impact of repeated ischemic time, and ethical considerations with allograft retransplantation. (Level of Difficulty: Intermediate.).

Cardiac Implantable Electronic Devices: A Window Into the Evolution of Conduction Disease in Cardiac Amyloidosis.

OBJECTIVES: This study characterized the relationship between conduction disease and cardiac amyloidosis (CA) through longitudinal analysis of cardiac implantable electronic device (CIED) data. BACKGROUND: Bradyarrhythmias and tachyarrhythmias are commonly reported in CA and may precede a CA diagnosis, although the natural history of conduction disease in CA is not well-described. METHODS: Patients with CA (transthyretin amyloidosis cardiomyopathy [ATTR-CM] and light-chain amyloidosis [AL-CA]) and a CIED were identified within the Duke University Health System. Patient characteristics at the time of implantation, including demographics and data relevant to CA diagnosis, cardiac imaging, and CIED were recorded. CIED interrogations were analyzed for pacing and atrial fibrillation (AF) burden, activity level, lead parameters, and ventricular arrhythmia incidence and/or therapy. RESULTS: Thirty-four patients with CA (7 with AL-CA, 27 with ATTR-CM [78% with wild-type]; 82% men) with median age of 75 years and a mean ejection fraction of 42 ± 13% had a CIED implanted for bradycardia (65%) or prevention of sudden cardiac death (35%). CIED implantation preceded CA diagnosis in 14 patients (41%). Over a mean follow-up of 3.1 ± 4.0 years, right ventricular sensing amplitudes decreased but did not result in device malfunction; lead impedances and capture thresholds remained stable. Between post-implantation years 1 and 5, mean ventricular pacing increased from 56 ± 9% to 96 ± 1% (p = 0.003) and AF burden increased from 2 ± 1.3 to 17 ± 3 h/day (p = 0.0002). Ventricular arrhythmias were common (mean episodes per patient per year: 6.7 ± 2.3 [ATTR-CM] and 5.1 ± 3.2 [AL-CA]) but predominately nonsustained; only 1 patient with AL-CA required implantable cardioverter-defibrillator therapy. CONCLUSIONS: Longitudinal analysis of CIED data in patients with CA revealed progressive conduction disease, with high AF burden and eventual dependence on ventricular pacing, although lead parameters remained stable. Ventricular arrhythmias were common but predominantly nonsustained, particularly in ATTR-CM.

Outcomes following cardioversion for patients with cardiac amyloidosis and atrial fibrillation or atrial flutter.

Atrial arrhythmias commonly occur in patients with cardiac amyloidosis (CA), but there is limited data on safety or efficacy of cardioversion (DCCV) for management of these rhythms in CA. We identified 25 patients with CA (20 with transthyretin (TTR) and 5 with light-chain (AL) amyloidosis) at Duke University who underwent DCCV for atrial arrhythmias and documented procedural success, complications, and long-term morbidity and mortality. While DCCV successfully restored sinus rhythm in 96% of patients, 36% of patients experienced immediate procedural complications (primarily bradycardia and hypotension), 80% had recurrence of atrial arrhythmias at 1 year, and 52% died at 3 years, highlighting short-term safety concerns, long-term inefficacy, and poor prognosis associated with symptomatic atrial arrhythmias requiring DCCV in CA.

Sleep Breathing Disorders in Heart Failure.

Sleep-disordered breathing (SDB), including obstructive sleep apnea, central sleep apnea (CSA), and Cheyne-Stokes respiration, is common in patients with heart failure (HF) and associated with lower left ventricular ejection fraction (EF), increased arrhythmia burden, and increased mortality. Continuous positive airway pressure therapy improves short-term and long-term outcomes in HF patients. Adaptive servoventilation (ASV) therapy in patients with low-EF HF with predominant CSA is not recommended. Ongoing trials are evaluating whether ASV will have a role in SDB treatment. Phrenic nerve stimulation is an emerging treatment option that has shown promising outcomes. All HF patients should be screened for SDB.

Predictors of Warfarin Time in Therapeutic Range after Continuous-Flow Left Ventricular Assist Device.

INTRODUCTION: Patients with a continuous-flow left ventricular assist device (CF-LVAD) require anticoagulation with a vitamin K antagonist to prevent thromboembolic events. Fluctuations in the international normalized ratio are associated with both increased thrombotic and bleeding episodes. To date, risk factors for low time in therapeutic range (TTR) among ambulatory patients with a CF-LVAD have not been explored. METHODS: A retrospective single-center analysis of 121 patients implanted with a CF-LVAD was performed. International normalized ratios were systematically recorded from the initial postdischarge outpatient visit to 12 months of time on the device. Risk factors for low TTR were evaluated using a multivariable linear regression analysis. Each of the 21 independent variables was entered into a stepwise regression designed to minimize the Akaike information criteria. RESULTS: In the multivariable analysis, the model output revealed that every 1-year increase in age was associated with a 0.4% increase in TTR (p=0.008), and every 1 mile further from clinic was associated with a 0.08% increase in TTR (p=0.03). Female sex was associated with a 10.1% decrease in TTR (p=0.04), type 2 diabetes was associated with an 11.5% decrease in TTR (p=0.006), and prior warfarin use was associated with an 8.3% decrease in TTR (p=0.03). CONCLUSION: In CF-LVAD recipients receiving warfarin, increasing age and distance from clinic are independent predictors of higher TTR. Female sex, type 2 diabetes, and prior warfarin use are independent predictors of lower TTR.