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Ventricular arrhythmias (VAs) are common after left ventricular assist device (LVAD) implantation though data are mixed on whether these events have an impact on mortality.The National Inpatient Sample (NIS) database from 2002-2019 was queried for LVAD implantation admissions. Secondary ICD codes were analyzed to assess for the occurrence of VAs during this admission. Propensity score matching (PSM) was used to control for confounding variables between those with versus without VAs.The NIS database from 2002-2019 contained 43 936 admissions with LVAD implantation. VAs occurred in 19 985 (45.4%) patients. After PSM, the study cohort consisted of 39 989 patients, 19 985 (50.0%) of which had a secondary diagnosis of VA during the admission. When compared to those without VA, those with VA were at no higher risk for in-hospital mortality (adjusted odds ratio 1.011, 99.9% CI 0.956-1.069, p = 0.699). Those with a VA were at higher risk for cardiogenic shock and requiring mechanical ventilation, tracheostomy, and percutaneous endoscopic gastrostomy placement. Patients with a VA were also at lower risk for device thrombosis. Conversely, the VA group was at no higher risk for stroke. In comparing trends from 2002 to 2019, the incidence of VAs has increased, while the mortality rate of those with and without VAs has decreased during this same period.In this retrospective study of the NIS database, VAs were common (45.4%) during the LVAD implantation admission. However, the occurrence of VAs during the implantation admission did not alter in-hospital mortality. More longitudinal studies are required to assess the long-term impact of VAs on mortality. In comparing trends from 2002-2019, the incidence of VAs has increased, while the mortality rate of those with and without VAs has decreased.

Background: Several factors affect heart (HTx) and lung (LTx) transplant program outcomes. Variability in institutional and community characteristics have been shown to influence survival. At present, currently, half of HTx centers in the United States do not possess a concomitant LTx program. This study sought to better understand the relationship of HTx with and without LTx programs. Methods: Nationwide transplant data were collected from the Scientific Registry of Transplant Recipients (SRTR) in August 2020. SRTR star rating ranges from tier 1 (lowest) to tier 5 (highest). HTx volumes and SRTR star ratings for survival were compared between the centers with heart-only (H0) programs and the centers with heart-lung (HL) programs. Results: SRTR star ratings were available for 117 Transplant centers with one or more HTx reported. The median number of HTx performed over one year was 16 (IQR: 2-29). Number of HL centers (n=67, 57.3%) were comparable to H0 centers (n=50, 42.7%) (p= 0.14). The HTx volume at HL centers [28 (IQR: 17-41)] exceeded HTx volume at H0 centers [13 (IQR: 9-23)], (p

Aims Atrial fibrillation (AF) in patients with cardiac amyloidosis (CA) has been linked with a worse prognosis. The current study aimed to determine the outcomes of AF catheter ablation in patients with CA. Methods and results The Nationwide Readmissions Database (2015–2019) was used to identify patients with AF and concomitant heart failure. Among these, patients who underwent catheter ablation were classified into two groups, patients with and without CA. The adjusted odds ratio (aOR) of index admission and 30-day readmission outcomes was calculated using a propensity score matching (PSM) analysis. A total of 148 134 patients with AF undergoing catheter ablation were identified on crude analysis. Using PSM analysis, 616 patients (293 CA-AF, 323 non-CA-AF) were selected based on a balanced distribution of baseline comorbidities. At index admission, AF ablation in patients with CA was associated with significantly higher adjusted odds of net adverse clinical events (NACE) [adjusted odds ratio (aOR) 4.21, 95% CI 1.7–5.20], in-hospital mortality (aOR 9.03, 95% CI 1.12–72.70), and pericardial effusion (aOR 3.30, 95% CI 1.57–6.93) compared with non-CA-AF. There was no significant difference in the odds of stroke, cardiac tamponade, and major bleeding between the two groups. At 30-day readmission, the incidence of NACE and mortality remained high in patients undergoing AF ablation in CA. Conclusion Compared with non-CA, AF ablation in CA patients is associated with relatively higher in-hospital all-cause mortality and net adverse events both at index admission and up to 30-day follow-up.

We present 3 cases of superior vena cava (SVC) syndrome following percutaneous right ventricular assist device (RVAD) placement. Each case underscores the importance of early recognition of SVC syndrome in patients with percutaneous RVAD insertion via the internal jugular vein and calls for heightened awareness of device-associated complications. (Level of Difficulty: Advanced.), Central Illustration

Solid organ transplant candidates encountered increased wait times and mortality rates during the coronavirus 2019 (COVID-19) pandemic. Despite improvement in medical management and vaccination efficacy, this patient population remains at increased risk for complications post COVID-19 including organ rejection. We describe the development of antibody mediated rejection with or without cellular rejection in heart transplant (HT) recipients and previous COVID-19 infection or vaccination. Although centers have changed their management of outpatient follow-up for orthotopic heart transplant (OHT) patients, little is known on surveillance of rejection and management of HT recipients after COVID-19 infection. We recommend frequent surveillance for rejection or allograft dysfunction after COVID-19 infection. We have adopted a transplant surveillance protocol for HT recipients with COVID 19 infection, given our recent experience with transplanted patients affected of COVID-19. This article is protected by copyright. All rights reserved.

Funding Information: This research was funded by the European Union Horizon 2020 research and innovation program under Grant Agreement No. 857470 and from the European Regional Development Fund via Foundation for Polish Science International Research Agenda PLUS program Grant No. MAB PLUS/2018/8. | openaire: EC/H2020/857470/EU//NOMATEN Equiatomic NiCoCr solid solutions have been shown by recent experiments and atomistic simulations to display exceptional mechanical properties that have been suggested to be linked to nanostructural short-range order (SRO) features that may arise from thermal treatments, such as annealing or/and aging. Here we use hybrid Monte Carlo-molecular dynamics simulations to gain further insights of thermal effects on the SRO formation as well as the edge dislocation plasticity mechanisms of equiatomic NiCoCr face-centered cubic solid solution. For that purpose, we utilize two well-known NiCoCr interatomic potentials, one of which displays well-documented SRO, believed to be linked to experimental evidence and labeled as the Li-Sheng-Ma potential, while the other (Farkas-Caro) does not. We use these two potentials to discern short-range ordering (from inherent randomness in random solid solutions) and understand how SROs influence dislocation depinning dynamics in various thermal annealing scenarios. In this context, we used robust, scale-dependent metrics to infer a characteristic SRO size in the Li-Sheng-Ma case by probing local concentration fluctuations which otherwise indicate uncorrelated patterns in the Farkas-Caro case in a close agreement with random alloys. Our Voronoi-based analysis shows meaningful variations of local misfit properties owing to the presence of SROs. Using relevant order parameters, we also report on the drastic increase of chemical ordering within the stacking fault region. More importantly, we find that the Li-Sheng-Ma potential leads to excellent edge dislocation depinning strength with low stacking fault width. Our findings indicate an enhanced roughening mechanism due to the SROs-misfit synergy that leads to significant improvements in dislocation glide resistance. We argue that the improvements in alloy strength have their atomistic origins in the interplay between nanoscopic SROs and atomic-level misfit properties.

Despite improved outcomes of modern continuous-flow left ventricular assist devices (CF-LVADs), device exchange is still needed for various indications. While the majority of CF-LVADs are exchanged to the same model, exchange to a different pump model is occasionally warranted. In this meta-analysis, we sought to consolidate the existing evidence to better elucidate the indications and outcomes in these cases. A comprehensive systematic search of adult patient cohorts who underwent CF-LVAD exchange to a different CF-LVAD model was performed. Study-level data from 10 studies comprising 98 patients were extracted and pooled for analysis. Mean patient age was 58 (95% CI: 48-65) and 81% were male. Indication for initial CF-LVAD was ischemic cardiomyopathy in 45% (34-57). Initial device was HeartMate II LVAD (HMII) in 93 (94.9%) and HeartWare HVAD (HW) in 5 (5.1%) patients. After mean CF-LVAD support time of 18.8 (15.2-22.4) months, exchange indications included thrombosis in 71% (43-89), infection in 21% (8-47) and device malfunction in 12% (7-21). HMII to HW exchange occurred in 53 (54.1%) patients, HMII to HeartMate III (HM3) in 32 (32.7%), and HM II to either HW or HM3 in 13 (13.2%) patients. Postoperatively, right ventricular assist device was required in 16% (8-32). Overall, 20% (8-40) of patients experienced a stroke, while HW patients had a significantly higher stroke incidence than HM3 patients (HW: 21% (8-47) vs. HM3: 5% (1-24), P < .01). Overall 30-day mortality was 10% (6-17), while HW had a significantly worse 30-day mortality than HM3 (HW: 13% (7-24) vs. HM3: 5% (1-24), P = .03). Following device exchange from a different CF-LVAD model, HM3 is associated with lower stroke and higher survival when compared to HW.

Heparin-induced thrombocytopenia (HIT) presents a unique challenge in patients requiring orthotopic heart transplantation (OHT). We sought to pool the existing evidence in a systematic review.Electronic search was performed to identify all relevant studies on OHT in patients with HIT. Patient-level data for 33 patients from 21 studies were extracted for statistical analysis.Median patient age was 51 [IQR 41, 55] years, with 75.8% (25/33) males. All patients had a clinical diagnosis of HIT, and anti-PF4/Heparin antibodies were positive in 87.9% (29/33). Median lowest reported platelet count was 46 × 10Heparin use during OHT may be associated with less adverse effects compared to use of other anticoagulants with no difference in 30-day mortality.

Introduction: Randomized controlled trials and systematic reviews evaluating the use of pulmonary artery catheters in the critically ill population have not shown beneficial effects on survival. However, many of those studies have excluded patients in cardiogenic shock. We address this evidence gap by providing a comprehensive meta-analysis to investigate the association between pulmonary artery catheter use and outcomes in patients with cardiogenic shock Hypothesis: Pulmonary artery catheter use in patients with cardiogenic shock is associated with improved mortality. Methods: We performed an extensive literature search using PubMed, MEDLINE, SCOPUS, and the Cochrane databases from January 1990 through June 2021. Data for final analysis was pooled using a random effects model. Odds ratios were used for effect size. Information on eligibility criteria, outcomes, and methodological quality was extracted by two independent reviewers. Primary study outcome was in-hospital mortality rate. Results: 16 studies were included in the analysis comprising 2,400,618 patients. Of those, 212,122 were managed with a pulmonary artery catheter (8.8%) and 2,188,496 were managed without one (91.2%). In patients with cardiogenic shock, pulmonary artery catheter use was associated with a statistically significant decrease in mortality (OR 0.82 [95% CI 0.73-0.92; p = 0.001]. The pulmonary artery catheter cohort was more likely to receive mechanical circulatory support (OR 2.16 [95% CI 1.90-2.45; p Conclusions: Pulmonary artery catheter use in patients with cardiogenic shock is associated with lower in-hospital mortality. Future studies differentiating pulmonary artery catheter use among various cardiogenic shock stages and phenotypes are needed.

Background: Catheter ablation for atrial fibrillation is a proven alternative to pharmacologic rhythm control in patients with heart failure with reduced ejection fraction (HFrEF). Whether outcomes differ in patients with heart failure with preserved ejection fraction (HFpEF) is of interest. Methods: Medline, Scopus, and Cochrane Central Register of Controlled Trials were systematically searched to identify relevant studies. We extracted or calculated a risk ratio (RR) and 95% confidence intervals (CI) from each study. Primary outcomes of interest include atrial arrythmia recurrence and repeat ablation. Harm outcomes of interest include all-cause mortality, all-cause hospitalizations, cardiovascular hospitalizations, stroke/transient ischemic attack, and cardiac tamponade. Results: We included 7 observational studies comprising 2,525 patients with HFpEF who underwent catheter ablation for atrial fibrillation. There were no significant differences in primary and harm outcomes when comparing catheter ablation for atrial fibrillation in patients with HFpEF to patients with no heart failure. Similarly, there were no significant differences in outcomes when comparing catheter ablation for patients with HFpEF to HFrEF. The certainty in these estimates was low. Conclusions: Non-randomized studies suggest that catheter ablation for atrial fibrillation in patients with HFpEF is associated with similar arrythmia free survival and safety profile when compared to patients with HFrEF and without heart failure. This suggests that patients with AF and HFpEF may benefit equally from catheter ablation as those with AF and HFrEF.

In the design and development of novel materials that have excellent mechanical properties, classification and regression methods have been diversely used across mechanical deformation simulations or experiments. The use of materials informatics methods on large data that originate in experiments or/and multiscale modeling simulations may accelerate materials discovery or develop new understanding of materials’ behavior. In this fast-growing field, we focus on reviewing advances at the intersection of data science with mechanical deformation simulations and experiments, with a particular focus on studies of metals and alloys. We discuss examples of applications, as well as identify challenges and prospects.

The use of low-dose aspirin (LDA) and heparin has improved pregnancy outcomes in women with antiphospholipid syndrome (APS). However, 20-30% still have adverse outcomes despite treatment. Recent retrospective studies showed a beneficial effect of hydroxychloroquine (HCQ) in APS due to its anti-inflammatory, immunomodulatory and antithrombotic properties. Data in refractory obstetric APS (OAPS) remain scarce and include heterogeneous populations with various concomitant treatments.The objective of this study was to assess the impact on the obstetric outcomes of adding HCQ to classical treatments for women with refractory primary obstetric APS.In a retrospective single-centre cohort study, we compared pregnancy outcomes in women with refractory primary OAPS (2004-2019) who received two different treatments in subsequent pregnancies. Group A received 400 mg HCQ + 60 mg enoxaparin + LDA, while Group B received 60 mg enoxaparin + LDA. The main outcome was live birth rates, while pregnancy complications (early and late pregnancy losses and placental-mediated complications) were the secondary outcome.A total of 101 pregnancies in 87 refractory primary OAPS patients were included. The rate of live-born babies in Group A (HCQ) was 97.1% (67/69) vs. 62.5% (20/32) in Group B (RR: 1.55 [95% CI, 1.19-2.1]; p 0.001). Pregnancy complications in Group A were 8.7% (6/69) vs. 37.5% (12/32) in Group B (RR 0.22 [95% CI, 0.15-0.30]; p 0.001).Hydroxychloroquine was associated with a higher rate of live births and a lower prevalence of pregnancy complications in refractory primary obstetric APS. The addition of HCQ to classical treatment may present a promising approach that needs to be confirmed with prospective studies.

Treatment of giant cell myocarditis (GCM) can require bridging to orthotopic heart transplantation (OHT) or recovery with mechanical circulatory support (MCS). Since the roles of MCS and immunotherapy are not well-defined in GCM, we sought to analyze outcomes of patients with GCM who required MCS. A systematic search was performed in June 2019 to identify all studies of biopsy-proven GCM requiring MCS after 2009. We identified 27 studies with 43 patients. Patient-level data were extracted for analysis. Median patient age was 45 (interquartile range (IQR): 32&ndash, 57) years. 42.1% (16/38) were female. 34.9% (15/43) presented in acute heart failure. 20.9% (9/43) presented in cardiogenic shock. Biventricular (BiVAD) MCS was required in 76.7% (33/43) of cases. Of the 62.8% (27/43) of patients who received immunotherapy, 81.5% (22/27) used steroids combined with at least one other immunosuppressant. Cyclosporine was the most common non-steroidal agent, used in 40.7% (11/27) of regimens. Immunosuppression was initiated before MCS in 59.3% (16/27) of cases, after MCS in 29.6% (8/27), and not specified in 11.1% (3/27). Immunosuppression started prior to MCS was associated with significantly better survival than MCS alone (p = 0.006), 60.5% (26/43) of patients received bridge-to-transplant MCS, 39.5% (17/43) received bridge-to-recovery MCS, 58.5% (24/41) underwent OHT a median of 104 (58&ndash, 255) days from diagnosis. GCM recurrence after OHT was reported in 8.3% (2/24) of transplanted cases. BiVAD predominates in mechanically supported patients with GCM. Survival and bridge to recovery appear better in patients on immunosuppression, especially if initiated before MCS.

Patient: Male, 46-year-old Final Diagnosis: Varicella zoster virus infection Symptoms: Abdominal and/or epigastric pain Medication:— Clinical Procedure: Biopsy Specialty: Cardiology • Gastroenterology and Hepatology • Infectious Diseases • Transplantology Objective: Rare disease Background: Acute pancreatitis is rare following solid organ transplantation but is associated with high mortality. It has been most commonly reported following renal transplant but can occur with other solid organ transplantations. Case Report: A 46-year-old male who had an orthotopic heart transplant 6 months ago presented with a 3-week history of abdominal pain. The patient described it as intermittent, sharp, and stabbing, originating in the periumbilical area and radiating to the back. His lipase was elevated at 232 U/L. Given that the patient’s symptoms and lipase were elevated to greater than three times the upper limit of normal, he patient was diagnosed with acute pancreatitis. The patient also mentioned a diffuse itchy rash that started a few days prior to admission. Dermatology was consulted, and given the man’s clinical presentation, there was concern for atypical reactivation of varicella zoster virus (VZV). VZV polymerase chain reaction of the vesicles returned positive. The patient was started on acyclovir and his symptoms improved. Conclusions: This is the first reported case of VZV-associated pancreatitis in a heart transplant patient. Our patient presented with acute pancreatitis and was treated supportively. However, he did not receive antiviral treatment until his rash was discovered. Timely treatment of VZV resulted in resolution of both the rash and pancreatitis. Timely diagnosis of pancreatitis and VZV is important to prevent development of multiorgan failure and death.

Background: Microsurgical and endoscopic approaches are accepted alternatives for the management of symptomatic arachnoid cyst. However, given their ability to visualize critical neurovascular structures with less morbidity, less dissection needs, and high success rates, endoscopic approaches are excellent options for the management of this pathology. Case Description: We present the case of an otherwise healthy 8-year-old male who presented with a chronic history of disabling headache that augmented with exercise and interrupted his sleep. He had a normal neurological examination. Neuroimaging studies depicted a right middle fossa Galassi III arachnoid cyst with no associated hydrocephalus, marked displacement of adjacent cortex, and apparent connection with the basal cisterns. Given the severity of the symptoms, and the size and compressive effect of the arachnoid cyst, surgical management through and endoscopic approach was undertaken. We performed a right temporal burr hole, right above the zygomatic arch to avoid vessels of the Sylvian fissure and to allow an optimal trajectory to the medial edge of the cyst and the target cisterns. We proceeded to identify the endoscopic anatomy of the surrounding structures to perform and adequate fenestration of multiple arachnoid membranes, obtaining an adequate cystocisternal communication. We then performed closure in a standard fashion. The patient was neurologically unchanged after the procedure and was discharged on postoperative day 2. The postoperative images revealed a dramatic reduction in the cyst dimensions with resolution of its compressive effect. Conclusion: Endoscopic management of arachnoid cyst offers several advantages such as the visualization of the cyst boundaries and critical adjacent structures, and the need for a less extensive dissection having a success rate between 83% and 92%. It is important to perform a wide multifocal fenestration as a key step to avoid cyst reclosure.

Purpose We sought to explore the short- and long-term outcomes of patients with severe PAD undergoing MCS. Methods We queried INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) database to identify patients undergoing LVAD implantation between June 2006 and December 2017. We then identified patients with PAD, defined in the database as co-morbidity and/or concern for patient treatment or contraindication for transplant. We further subdivided this cohort by presence of severe diabetes. Results We identified 15,162 patients who underwent LVAD implantation during the study period, out of which, 699 patients had severe PAD. Compared to patients without PVD, patients with PAD were older, greater proportion of male, more likely to have ischemic etiology. History of severe DM, stroke, pulmonary disease, and chronic kidney disease, and current smoking were reported more frequently in patients with PAD. Median follow-up duration was 12.8 months (IQR 5.2-25.8). Kaplan Meier analysis demonstrated that presence of PAD was associated with substantial increase in mortality (41.9% vs 27.5%, p Conclusion Severe PAD is associated with a substantially increased in early and late mortality after LVAD implantation. Further studies are needed to better ascertain the cause of mortality in this patient cohort.

Introduction Cardiac amyloidosis is an under recognized cause of cardiomyopathy leading to progressive heart failure from deposition of misfolded protein in the myocardial extracellular matrix. AL and ATTR amyloidosis are the main forms of cardiac amyloidosis accounting for >90% of cases in the U.S. Case Report A 57 year old woman with hypertension, bilateral carpal tunnel and recent diagnosis of heart failure was transferred for evaluation. She presented to her PCP three months prior with pedal edema. Echocardiogram at that time showed an LVEF of 55% and she was diagnosed with HFpEF. She was hospitalized twice for progressive symptoms; coronary angiography showed luminal irregularities intracardiac pressures were notable for RAP of 23 mmHg, RVP of 41/11 mmHg, PAP 42/25 mmHg, PCWP of 31 mmHg with CO of 3.2 L/min. MRI was recommended but not attained. On admission, ECG showed sinus tachycardia and low voltage. TTE showed biventricular hypertrophy with LVEF 40%, biatrial enlargement and thickened mitral valve with restrictive inflow pattern concerning for amyloidosis. UPEP demonstrated a monoclonal spike with serum lambda free light chains of 1721 mg/L and κ/λ ratio of Summary AL amyloidosis is a multiorgan disease in which one system usually predominates with cardiac involvement portending the worst prognosis. It is irreversible and can be rapidly fatal; early work-up and recognition is crucial as therapies exist.

Purpose The PARADIGM-HF trial analyzed the effect of sacubitril/valsartan on cardiovascular mortality and heart failure hospitalizations. A sub-analysis of PARADIGM-HF demonstrated more diuretic dose reductions in those taking sacubitril/valsartan versus enalapril. Real world data is still limited in terms of analysis of diuretic dose adjustments in patients after being maintained on a dose of sacubitril-valsartan for a fixed period. This study hypothesizes that maintenance on sacubitril/valsartan leads to lower diuretic dose requirements. Methods Single-center retrospective chart review of patients initiated and maintained on any dose of sacubitril-valsartan from January 1, 2016 to October 1, 2019 while on a concomitant loop diuretic. Patient clinical outcomes and loop diuretic requirements were analyzed for three months following maintenance on any dose of sacubitril/valsartan for four weeks. Chart reviews were done to examine for changes in heart failure symptoms, adjustments in guideline-directed medical therapies, and baseline angiotensin-converting enzyme inhibitor (ACEI)/ angiotensin receptor blocker (ARB) therapies prior to sacubitril/valsartan initiation. Safety endpoints included symptomatic hypotension, hyperkalemia and elevated serum creatinine. Results A total of 110 patients were included in the analysis. Ninety-nine patients were on an ACEI/ARB prior to initiation of sacubitril/valsartan while eleven were started de novo. Fifty-eight patients (52.7%) were titrated to maximum dose, 32.7% (36/110), were at intermediate dose, 10.9% (12/110) at low-dose, and 4.5% (5/110) were discontinued. Ten patients (9.1%) required discontinuation of loop diuretics and 36.4% (40/110) of patients required loop diuretic dose reductions when compared to the diuretic requirement at the time of sacubitril/valsartan initiation. The mean diuretic dose was reduced from 63.4 mg (±54.3) pre-sacubitril/valsartan to 50.6 mg (± 54.5) post-sacubitril/valsartan in furosemide equivalents, P Conclusion Significant diuretic dose reductions were observed in patients after maintenance on sacubitril/valsartan. This retrospective study serves as an example of real-world experience of diuretic requirements in patients initiated on sacubitril/valsartan.

Purpose Guideline directed medical therapy with beta blockers, ACEi/ARBs, and aldosterone antagonists with the goal of affecting cardiac reverse remodeling (CRR) has previously been the cornerstone of management of patients with heart failure with reduced ejection fraction (HFrEF). More recently, PARADIGM-HF demonstrated the superiority of sacubitril-valsartan to enalapril in reducing HF hospitalizations as well as cardiac and all-cause mortality. Other studies demonstrated that ARNI therapy may enhance CRR to a greater degree than ACEI or ARB therapy alone. To date, the degree of CRR in nonischemic vs ischemic cardiomyopathy treated with ARNI has not been studied. Methods A single-center retrospective chart review was performed assessing the effect of ARNI on echocardiographic parameters of CRR. Patients initiated on any dose sacubitril-valsartan from January 1, 2016 to October 1, 2019 were included. Baseline demographic and clinical information was collected. Serial echocardiograms performed at 3 month intervals following initiation of therapy were reviewed for markers of cardiac remodeling including ejection fraction (LVEF), left ventricular internal diameter end diastole and end systole (LVESD, LVEDD), and left ventricular mass index (LVMI). Results Of the 76 patients included in the analysis, 29 (38%) had ICM and 47 (72%) had NICM with a median age of 61.5. Both groups were treated with maximally tolerated doses of guideline directed medical therapy. There was no difference in the percentage of patients in each cohort treated with low, intermediate, or high doses of ARNI. Patients with ICM and NICM were treated with ARNI for an average of 1.7 years and 1.6 years respectively. In the ICM cohort, there was a statistically significant improvement in LVEF (P=0.004), but not in any other parameters of ventricular remodeling. In the NICM cohort, there was a statistically significant improvement in LVEF (P=0.007), LVESD (P=0.004), and LVMI (P=0.007). Conclusion Our data suggest that less LV remodeling occurs in ICM vs NICM following treatment with ARNI. A subgroup analysis of PARADIGM-HF demonstrated similar clinical outcomes in these two patient populations. Taken together, these findings raise the possibility that the benefit of ARNI therapy occurs through mechanisms in addition to reverse remodeling.

Variable age thresholds are often used at transplant centers for simultaneous heart and kidney transplantation (HKT). We hypothesize that selected older recipients enjoy comparable outcome to younger recipients in the current era of HKT.We performed a retrospective analysis of HKT outcomes in the United Network for Organ Sharing (UNOS) registry from 2006 to 2018, classifying patients by age at transplant as ≥ 65 or 65 years. The primary outcome was patient death. Secondary outcomes included all-cause kidney graft failure and death-censored kidney allograft failure.Of 973 patients, 774 (80%) were younger than 65 years (mean 52 ± 10 years) and 199 (20%) were 65 years or older (mean 67 ± 2 years). The older HKT cohort had fewer blacks (22% vs 35%, P = .01) and women (12 vs 18%, P = .04). Fewer older patients received dialysis (30% vs 54%, P .001) and mechanical support (36% vs 45%, P = .03) before HKT. Older recipients received organs from slightly older donors. The median follow-up time was shorter for patients 65 years or older than for the younger group (2.3 vs 3.3 years, P .001). Patient survival was similar between the groups (mean 8.8 vs 9.8 years, P = .3), with the most common causes of death being cardiovascular (29%) and infectious complications (28%). There was no difference in all-cause kidney graft survival (mean 8.7 vs 9.3 years, P = .8). Most commonly, recipients died with a functional renal allograft (59.8%), and this occurred more commonly in older patients (81.4% vs 54.8%, P = .001). Cox proportional hazard modeling showed that higher donor age (hazard ratio [HR] 1.015, P = .01; HR 1.022, P = .02) and use of pre-transplant dialysis (HR 1.5, P = .004; HR 1.8, P = .006) increased the risk for both all-cause and death-censored kidney allograft failure, respectively.Our study showed that carefully selected older patients have outcomes similar to those of a younger cohort and argues for comprehensive evaluation of the recipients with age as part of comorbidity assessment rather than use of an arbitrary age threshold for candidacy.

Purpose Cardiac mass ratio (CMR) is validated for donor-recipient sizing, and as a predictor of transplant outcomes. However, there is a lack of data reviewing the role CMR plays in transplant recipients with pulmonary hypertension (pHTN). In particular, the right ventricular (RV) mass ratio (RVMR) is a component of CMR not yet studied separately for this purpose. We aimed to review the relationship of CMR and RVMR with pHTN in terms of development of primary graft dysfunction (PGD) and overall survival. Methods The United Network for Organ Sharing (UNOS) database was queried for primary heart transplant patients from 1987 to 2020. Missing data was imputed using a Bayesian network. Left ventricular (LV), RV, total cardiac mass (CM), and their ratios were calculated for donors and recipients. Relevant hemodynamic variables were included in logistic regression and cox proportional-hazards models to evaluate a relationship to PGD and overall survival. A stepwise regression created parsimonious models. Covariates with statistically significant relationships to the outcomes were included in tensor product spline models. Results 62,169 patients were identified. A parsimonious logistic model for odds of PGD included RVMR (OR 0.99, p Conclusion In patients with pHTN, RVMR is significantly associated with odds of developing PGD, and CMR is with overall survival. Some RV oversizing may be beneficial to mitigate the risk of PGD.

ATTR amyloidosis is a systemic, debilitating and fatal disease caused by transthyretin (TTR) amyloid accumulation. RNA interference (RNAi) is a clinically validated technology that may be a promising approach to the treatment of ATTR amyloidosis. The vast majority of TTR, the soluble precursor of TTR amyloid, is expressed and synthesized in the liver. RNAi technology enables robust hepatic gene silencing, the goal of which would be to reduce systemic levels of TTR and mitigate many of the clinical manifestations of ATTR that arise from hepatic TTR expression. To test this hypothesis, TTR-targeting siRNAs were evaluated in a murine model of hereditary ATTR amyloidosis. RNAi-mediated silencing of hepatic TTR expression inhibited TTR deposition and facilitated regression of existing TTR deposits in pathologically relevant tissues. Further, the extent of deposit regression correlated with the level of RNAi-mediated knockdown. In comparison to the TTR stabilizer, tafamidis, RNAi-mediated TTR knockdown led to greater regression of TTR deposits across a broader range of affected tissues. Together, the data presented herein support the therapeutic hypothesis behind TTR lowering and highlight the potential of RNAi in the treatment of patients afflicted with ATTR amyloidosis.

Background Ventricular tachycardia (VT) has been described in patients who have undergone implantation of ventricular assist devices (VAD). Mechanisms for VT in these patients include scar-mediated reentry, bundle branch reentry, and mechanically-induced arrhythmia related to scar caused by VAD inlet cannula placement or suction events. While the hemodynamic support offered by VAD's can mitigate the harmful effects of ventricular tachyarrhythmias, morbidity can arise from outcomes including RV failure. VT ablation has been utilized with some success in these patients though data in this area is scarce, especially in those with biventricular support devices. Case Report We present a case of a 47 year-old man with a history of hypertension, tobacco and cocaine abuse presenting with STEMI. Despite emergent catheterization with PCI to proximal LAD lesion, he developed cardiogenic shock requiring intra-aortic balloon pump placement. He subsequently suffered V Fib arrest necessitating upgrade to VA-ECMO. Due to persistent biventricular failure with inability to wean support, he was transitioned to durable left ventricular support (Heartmate 3, Abbott) and temporary right ventricular support (Protek Duo, TandemLife). Despite durable support, he remained in VT refractory to antiarrhythmic agents (Amiodarone, Lidocaine, Procainamide), multiple cardioversions, and stellate ganglion block. Given incessant VT leading to RV failure and compromising RVAD removal, the decision was ultimately made to proceed with VT ablation. The patient underwent extensive substrate-based ablation and ablation of the right bundle and left posterior fascicle for bundle branch reentry and interfascicular VT complicated by transient AV block requiring TVP insertion. Other complicating factors involved in this procedure included gaining access and manipulating ablation catheters given presence of prior devices including the LVAD cannula. At the end of the procedure the patient had no further inducible VT. He was successfully weaned off of RVAD support after the ablation. His hospital course was complicated by recurrent slower VT which was successfully managed with medical therapy. Conclusions Our case highlights several complicating factors in managing ventricular tachyarrhythmias in patients with mechanical circulatory support devices. These include limitations to medical management due to side effect profiles or refractoriness, coordination of multiple disciplines (advanced heart failure, EP, VAD team, anesthesia), as well as barriers to successful ablation including technical difficulty given the presence of other devices, the desire to avoid invasive procedures in patients susceptible to or suffering from systemic infection, and high recurrence rates. In this specific case VT ablation was successful in facilitating the goal of weaning the patient off of RVAD support.

Antibody-mediated rejection (AMR) of cardiac allografts mediated by anti-HLA Donor Specific Antibodies (DSA) is one of the major barriers to successful transplantation for the treatment of end-stage heart failure. Therapeutic plasma exchange (TPE) is a first-line treatment for pre-transplant desensitization. However, indications for treatment regimens and treatment end-points have not been well established. In this study, we investigated how sera dilutions could guide TPE regimens for effective peri-operative desensitization and early AMR treatment. Our data show that 1:16 dilutions of EDTA-treated sera and 1.5 volume TPE reduce anti-HLA class I and class II antibody levels in the same manner and, therefore, allows to predict which antibodies would respond to peri-operative TPE. We successfully applied this approach to transplanting three highly sensitized cardiac recipients (CPRA 85-93%) with peri-operative desensitization based on a virtual crossmatch performed on 1:16 diluted serum. Furthermore, we have used sera dilutions to guide DSA treatment post-transplant. Although these findings have to be confirmed in a larger prospective study, our data suggest that serum dilutions can serve as a predictive biomarker to guide peri-operative desensitization and post-transplant immunologic management.

Introduction Pulmonary hypertension (pHTN) complicating structural heart disease leads to distinct diagnostic and management dilemmas. We present a case of severe pulmonary hypertension in the setting of perimembranous VSD and severe AS. Case Report 76 yo female with restrictive VSD and severe AS presented with heart failure. Cardiac findings included RV heave and AS murmur. TTE revealed normal EF with severe pHTN, severe RV dysfunction, and severe AS. Her perimembranous septum was aneurysmal, with systolic jet velocity of 4.5 m/s. There was no CAD. RHC demonstrated PAP of 96/38/57 mmHg, PVR of 7.2 WU, PCWP 23 mmHg, CI of 3.04, and Qp/Qs of 1.1. The PCWP and PVR indicated pre- and post-capillary pHTN due to longstanding AS. She was deemed inoperable and was high risk for TAVR given aortic annular continuity with the VSD and ∼25% annular deficiency. There was concern that her elevated LVEDP was masking Eisenmenger physiology, and that relieving the AS may precipitate hypoxia. Balloon aortic valvuloplasty (BAV) was performed as bridge to decision. This enabled assessment of the integrity of the aortic annulus, the pulmonary pressure response to LV unloading, and development of right to left shunting after a decrease in LVEDP. Successful BAV was performed, and the patient was discharged. Following improvement in both PA pressures and her symptoms, a TAVR was offered. A self-expanding valve was selected to minimize risk of annular rupture. After successful deployment, her PAP were 78/42/54 and PCWP 23. She was diuresed and discharged. Summary Our case highlights important points in management of such complex patients with pHTN. Careful evaluation of hemodynamics is paramount in guiding decision making. The preserved PAPi with minimal shunting suggested the VSD was not significantly contributing to the severe pHTN. Additionally, BAV plays an important role as a bridge to determine potential response to TAVR. Although patients with WHO II pHTN can develop an irreversible pre-capillary component, such assessment can only be made following durable reduction in LVEDP. Lastly, interdisciplinary patient care is essential. Successful management of our patient required input from a multidisciplinary team consisting of pulmonology, structural cardiology, critical care cardiology and heart failure.

Purpose Giant cell myocarditis (GCM) is a rare, serious form of myocarditis that can require bridging to orthotopic heart transplant (OHT) with mechanical circulatory support (MCS). Given that the roles of MCS and immunosuppressive therapy have not been well defined in this patient population, we sought to analyze the outcomes of patients with GCM who required MCS. Methods A systematic search was performed in June 2019 to identify all studies of biopsy-proven GCM requiring MCS in the English literature after 2009. 27 studies were identified consisting of 43 patients. Patient-level data were extracted for statistical analysis. Results Median patient age was 45 [IQR: 32 - 57] years, and 42.1% (16/38) of patients were female. 34.9% (15/43) of patients presented with symptoms of acute heart failure, and 20.9% (9/43) presented in cardiogenic shock. Biventricular (BiVAD) MCS was required in 76.7% (33/43) of cases. The final diagnosis of GCM was made using endomyocardial biopsy in 72.1% (31/43) of cases, left ventricular apical core biopsy in 23.3% (10/43) of cases, and biopsy of the explanted heart in 2.3% (1/43) of cases. An immunosuppressive regimen was used in 62.8% (27/43) of cases. Of these patients, 81.5% (22/27) received steroids in combination with at least one other immunosuppressant, of which cyclosporine was the most common, administered to 40.7% (11/27) of patients. Immunosuppression was initiated before MCS in 59.3% (16/27) of cases, after MCS in 29.6% (8/27) of cases, and not specified in 11.1% (3/27) of cases. Survival stratified by immunosuppression (Panel A) and mode of MCS (Panel B) is shown. 58.5% (24/41) underwent OHT with a median time to transplant of 104 [58 - 255] days from diagnosis, and 46 [18 - 201] days from the initiation of MCS. Recurrence of GCM after OHT was reported in 8.3% (2/24) of cases. Conclusion Non-dischargeable BiVAD predominates in mechanically supported patients with GCM. Survival appears to be better in patients on immunosuppression, especially if initiated before MCS.

Purpose Previous studies have demonstrated a correlation between increasing center volume and improved post heart transplant (HTx) survival. We performed a contemporary analysis to evaluate this relationship. Methods The UNOS database was analyzed to include adult (≥18 years) HTx recipients from years 2006 to 2016. Each center had to perform >65 transplants to be included. Centers were categorized based on annual transplant volume: 6-15, 16-25, 26- 39 and ≥40. Primary endpoint was one-year mortality or retransplantation. Survival analysis was performed using Kaplan-Meier method. Adjusted analysis were performed using Cox-regression modeling. Results Among 17,853 HTx recipients, distribution of patients was 32.1%, 30.8%, 14.5% and 22.6% in the order of increasing center Htx volume, respectively. Median recipient age was 56 years (IQR 47-63) and 75.5% were male. Primary endpoint of one-year mortality or retransplantation was similar across the centers irrespective of transplant volume (6-15/yr: 10.4%, 16-25/yr: 9.5%, 26-39/yr: 11.1%, ≥40/yr: 9.7%; χ2 p=0.10 and Log-rank p=0.11) as noted in figure 1. When adjusted for recipient and donor risk factors, the Cox-regression analysis showed that centers with ≥40 Htx/yr had a lower rate of one-year mortality/retransplantation (HR 0.86; 95% CI 0.75-0.98; p=0.029) compared to patients at centers with volume 6-15/yr. The two remaining categories 16-25/yr (HR 0.94; p=0.31) and 26-39/yr (HR 1.06; p=0.43) showed no difference in primary endpoint when compared to the lowest volume category (6-15 /yr). Conclusion There was no difference in baseline rate of mortality or retransplantation at 1-year among Htx centers irrespective of volume. Among all categories, only centers with ≥40 Htx/yr had an improved risk adjusted primary endpoint compared to the centers with lowest volume. The correlation between increasing center volume and improved survival appears to have weakened in this updated analysis among US transplant centers.