Association between Impella device support and elevated rates of gout flares: a retrospective propensity-matched study.

BACKGROUND: Impella is an advanced ventricular assist device frequently used as a bridge to heart transplantation. The association of Impella with increased rates of gout flares has not been studied. Our primary aim is to determine the rates of gout flares in patients on Impella support. METHODOLOGY: A retrospective study was conducted between January 2017 and September 2022 involving all patients who underwent heart transplantation. The cohort was divided into two groups based on Impella support for statistical analysis. In patients receiving Impella support, outcome measures were compared based on the development of gout flares. 1:1 nearest neighbor propensity match, as well as inverse propensity of treatment weighted analyses, were performed to explore the causal relationship between impella use and gout flare in our study population. RESULTS: Our analysis included 213 patients, among which 42 (19.71%) patients were supported by Impella. Impella and non-Impella groups had similar age, race, and BMI, but more males were in the Impella group. Gout and chronic kidney disease were more prevalent in Impella-supported patients, while coronary artery disease was less common. The prevalence of gout flare was significantly higher in Impella patients (30.9% vs. 5.3%). 42 Impella-supported patients were matched with 42 patients from the non-impella group upon performing a 1:1 propensity matching. Impella-supported patients were noted to have a significantly higher risk of gout flare (30.9% vs. 7.1%, SMD = 0.636), despite no significant difference in pre-existing gout history and use of anti-gout medications. Impella use was associated with a significantly increased risk of gout flare in unadjusted (OR 8.07), propensity-matched (OR 5.83), and the inverse propensity of treatment-weighted analysis (OR 4.21). CONCLUSION: Our study is the first to identify the potential association between Impella support and increased rates of gout flares in hospitalized patients. Future studies are required to confirm this association and further elucidate the biological pathways. It is imperative to consider introducing appropriate measures to prevent and promptly manage gout flares in Impella-supported patients.

Transcatheter edge-to-edge repair for tricuspid valve regurgitation in apolipoprotein A-I-associated cardiac amyloidosis: case report.

Background: Amyloidosis is defined by abnormal protein folding and subsequent deposition in tissues. Cardiac involvement is usually related to misfolded monoclonal immunoglobulin light chains or misfolded transthyretin; however, apolipoprotein A-1-associated amyloidosis is a hereditary form of amyloidosis resulting from mutations in the AAPOA1 gene that can also result in cardiac amyloidosis. Although there have been advancements in noninvasive algorithms for the diagnosis of cardiac amyloidosis, endomyocardial biopsy (EMB) may still be warranted. All individuals undergoing EMB are susceptible to complications, including tricuspid valve injury resulting in severe tricuspid valve regurgitation. Case summary: Our patient is a 70-year-old white man presented with symptoms of dyspnoea on exertion and decreased functional capacity, diagnosed previously with apolipoprotein A-I cardiac amyloidosis, confirmed by EMB. He developed progressive right-sided heart failure secondary to iatrogenic flail tricuspid leaflet related to the diagnostic EMB. He underwent a successful transcatheter tricuspid valve edge-to-edge repair with 4D intracardiac echocardiographic guidance. At the recent follow-up, the patient showed improved symptoms, with increased stamina, and transoesophageal echocardiography revealed a 65% ejection fraction and mild tricuspid regurgitation (TR). Discussion: Tricuspid valve injury is one of the complications associated with EMB, which can result in severe TR. Transcatheter tricuspid valve edge-to-edge repair can be a useful option for patients considered too high risk for surgical intervention, such as those with advanced cardiac amyloidosis.

Donation after circulatory death: A transplant cardiologist's take on neuroprognostication.

Donation after circulatory death (DCD) is becoming increasingly utilized in heart transplantation and has the potential to further expand the donor pool. As transplant cardiologists gain more familiarity with DCD donor selection, there are many issues that lack consensus including how we incorporate the neurologic examination, how we measure functional warm ischemic time (fWIT), and what fWIT thresholds are acceptable. DCD donor selection calls for prognostication tools to help determine how quickly a donor may expire, and in current practice there is no standardization in how we make these predictions. Current scoring systems help to determine which donor may expire within a specified time window either require the temporary disconnection of ventilatory support or do not incorporate any neurologic examination or imaging. Moreover, the specified time windows differ from other DCD solid organ transplantation without standardization or strong scientific justification for these thresholds. In this perspective, we highlight the challenges faced by transplant cardiologists as they navigate the muddy waters of neuroprognostication in DCD cardiac donation. Given these difficulties, this is also a call to action for the creation of a more standardized approach to improve the DCD donor selection process for appropriate resource allocation and organ utilization.

Hereditary transthyretin amyloidosis presenting with spontaneous periorbital purpura: a case report.

Background: Amyloidosis is a systemic disorder of abnormal protein folding and deposition resulting in a range of symptoms including neuropathy, heart failure, renal disease, and dermatologic findings. The two most common types of amyloidosis that affect the heart are transthyretin (ATTR) amyloidosis and light chain (AL) amyloidosis, which vary in clinical presentation. Skin findings such as periorbital purpura are considered more specific for AL amyloidosis. However, there are rare cases of ATTR amyloidosis causing the same dermatologic findings. Case Summary: A 69-year-old female presented for evaluation of amyloidosis after cardiac imaging done at the time of a recent atrial fibrillation ablation showed signs of infiltrative disease. On examination, she had periorbital purpura which she reportedly had for years without receiving a diagnosis, as well as macroglossia with teeth indentation. These exam findings, in addition to her transthoracic echocardiogram showing apical sparing, are typically considered characteristic of AL amyloidosis. Subsequent workup revealed the presence of hereditary ATTR (hATTR) amyloidosis with a heterozygous pathogenic variant in the TTR gene producing the p.Thr80Ala mutation. Conclusion: Spontaneous periorbital purpura is thought to be pathognomonic for AL amyloidosis. However, we describe a case of hereditary ATTR amyloidosis with the Thr80Ala TTR genetic variant presenting initially with periorbital purpura, the first case documented in the literature to our knowledge.

Sex and gender differences in myocarditis and dilated cardiomyopathy: An update.

In the past decade there has been a growing interest in understanding sex and gender differences in myocarditis and dilated cardiomyopathy (DCM), and the purpose of this review is to provide an update on this topic including epidemiology, pathogenesis and clinical presentation, diagnosis and management. Recently, many clinical studies have been conducted examining sex differences in myocarditis. Studies consistently report that myocarditis occurs more often in men than women with a sex ratio ranging from 1:2-4 female to male. Studies reveal that DCM also has a sex ratio of around 1:3 women to men and this is also true for familial/genetic forms of DCM. Animal models have demonstrated that DCM develops after myocarditis in susceptible mouse strains and evidence exists for this progress clinically as well. A consistent finding is that myocarditis occurs primarily in men under 50 years of age, but in women after age 50 or post-menopause. In contrast, DCM typically occurs after age 50, although the age that post-myocarditis DCM occurs has not been investigated. In a small study, more men with myocarditis presented with symptoms of chest pain while women presented with dyspnea. Men with myocarditis have been found to have higher levels of heart failure biomarkers soluble ST2, creatine kinase, myoglobin and T helper 17-associated cytokines while women develop a better regulatory immune response. Studies of the pathogenesis of disease have found that Toll-like receptor (TLR)2 and TLR4 signaling pathways play a central role in increasing inflammation during myocarditis and in promoting remodeling and fibrosis that leads to DCM, and all of these pathways are elevated in males. Management of myocarditis follows heart failure guidelines and there are currently no disease-specific therapies. Research on standard heart failure medications reveal important sex differences. Overall, many advances in our understanding of the effect of biologic sex on myocarditis and DCM have occurred over the past decade, but many gaps in our understanding remain. A better understanding of sex and gender effects are needed to develop disease-targeted and individualized medicine approaches in the future.

Non-invasive detection of cardiac allograft rejection among heart transplant recipients using an electrocardiogram based deep learning model.

Aims: Current non-invasive screening methods for cardiac allograft rejection have shown limited discrimination and are yet to be broadly integrated into heart transplant care. Given electrocardiogram (ECG) changes have been reported with severe cardiac allograft rejection, this study aimed to develop a deep-learning model, a form of artificial intelligence, to detect allograft rejection using the 12-lead ECG (AI-ECG). Methods and results: Heart transplant recipients were identified across three Mayo Clinic sites between 1998 and 2021. Twelve-lead digital ECG data and endomyocardial biopsy results were extracted from medical records. Allograft rejection was defined as moderate or severe acute cellular rejection (ACR) based on International Society for Heart and Lung Transplantation guidelines. The extracted data (7590 unique ECG-biopsy pairs, belonging to 1427 patients) was partitioned into training (80%), validation (10%), and test sets (10%) such that each patient was included in only one partition. Model performance metrics were based on the test set (n = 140 patients; 758 ECG-biopsy pairs). The AI-ECG detected ACR with an area under the receiver operating curve (AUC) of 0.84 [95% confidence interval (CI): 0.78-0.90] and 95% (19/20; 95% CI: 75-100%) sensitivity. A prospective proof-of-concept screening study (n = 56; 97 ECG-biopsy pairs) showed the AI-ECG detected ACR with AUC = 0.78 (95% CI: 0.61-0.96) and 100% (2/2; 95% CI: 16-100%) sensitivity. Conclusion: An AI-ECG model is effective for detection of moderate-to-severe ACR in heart transplant recipients. Our findings could improve transplant care by providing a rapid, non-invasive, and potentially remote screening option for cardiac allograft function.

18F-FDG/13N-ammonia cardiac PET findings in ATTR cardiac amyloidosis.

18F-flurodeoxyglycose (FDG)/13N-ammonia positron emission tomography/computed tomography (PET/CT) is frequently utilized to evaluate cardiac sarcoidosis (CS) but findings can reflect other forms of myocardial inflammation or altered myocardial metabolic activity. Herein, we present five cases where cardiac PET findings suggested CS, but right ventricular endomyocardial biopsy samples revealed ATTR-type cardiac amyloidosis.

Association of Pulmonary Hypertension and Monoclonal Gammopathy of Undetermined Significance.

Objective: To determine the prevalence of monoclonal gammopathy of undetermined significance (MGUS) in patients with PH as well as precapillary PH. Methods: Olmsted County residents with PH, diagnosed between 1/1/1995 and 9/30/2017, were identified, and age and sex were matched to a normal control group. The PH group and normal control group were then cross-referenced with the Mayo Clinic MGUS database. Charts were reviewed to verify MGUS and PH. Heart catheterization data were then analyzed in these patients for reference to the gold standard for diagnosis. Results: There were 3419 patients diagnosed with PH by echocardiography between 1995 and 2017 in Olmsted County that met the criteria of our study. When the PH group (N = 3313) was matched to a normal control group (3313), a diagnosis of MGUS was significantly associated with PH 10.2% (OR = l.84 [95% CI 1.5-2.2], p < 0.001), compared with controls 5.8% based on echo diagnosis. Using heart catheterization data (484 patients), a diagnosis of MGUS was associated with PH 13.0% (OR = 3.94 [95% CI 2.28-6.82], p < 0.001). For pulmonary artery hypertension (N = 222), a diagnosis of MGUS was associated with PH at similar 12.2% (OR = 4.50 [95%CI 1.86-10.90], p < 0.001. Conclusions: There is a higher prevalence of MGUS in patients with PH and precapillary PH compared with normal controls. This association cannot be explained fully by other underlying diagnoses associated with PH. Assessing for this in patients with PH of unclear etiology may be reasonable in the workup of patients found to have PH.

Heart transplantation in Val142Ile mutation in the modern era: A single center experience.

Little is known about the post heart transplantation management of extra cardiac manifestations in patients with hereditary transthyretin amyloid cardiomyopathy (hATTR-CM) in the new era of disease modifying treatment for ATTR amyloidosis. This is a retrospective study of all patients with hATTR-CM associated with the Val142Ile variant who underwent heart transplantation (HT) from January 2014 to February 2022. All 10 patients with the Val142Ile mutation were successfully transplanted, with a 1 year survival post heart transplantation (HT) of 90%, comparable to an age, sex, and race matched cohort of patients transplanted for non-amyloid indications. However, 4 (40%) of these patients developed progressive extracardiac manifestations requiring initiation of TTR silencer therapy with the small interfering RNA (siRNA) drug patisiran, which was well tolerated with no significant side effects in this population. We recommend formal neurologic evaluation and assessment of extracardiac manifestations annually as part of routine post-transplant care, and disease modifying therapy, aimed at TTR stabilization or silencing, should be initiated in the context of previously untreated extracardiac manifestations or evidence of subclinical neuropathy to prevent progression.

Ventricular arrhythmia burden and implantable cardioverter-defibrillator outcomes in transthyretin cardiac amyloidosis.

BACKGROUND: As targeted treatments for amyloid transthyretin cardiomyopathy (ATTR-CM) are becoming available, we aim to characterize the rates of ventricular arrhythmias (VAs), implantable cardioverter-defibrillator (ICD) utilization, and their impact on survival. METHODS: This is a retrospective cohort study of 130 patients with ATTR-CM diagnosed at Emory University's Cardiac Amyloidosis Center between April 2012 and September 2020. VAs were defined as nonsustained or sustained ventricular tachycardia and ventricular fibrillation. RESULTS: Of 130 patients, 42 had wild-type disease (wtATTR) and 88 had hereditary variants (hATTR), most commonly Val122Ile (89%). At ATTR-CM diagnosis, 80 (62%) patients had EF ≤ 40% consistent with systolic heart failure. Of the 69 (53%) patients with documented VAs significantly higher rates occurred among those with EF ≤ 40% compared with EF > 40% (67% vs. 28%, p = .001). Thirty-two patients (25 hATTR, 7 wtATTR) had primary prevention ICDs implanted. Eight (25%) of these patients received appropriate ICD therapy while two (6%) experienced inappropriate therapy. Comparing patients with EF ≤ 35% with and without ICDs did not reveal any survival difference (3.3 ± 0.5 vs. 2.8 ± 0.4 years, p = .699). CONCLUSIONS: High rates of VAs and appropriate ICD therapy were found among a unique cohort of largely hereditary ATTR-CM patients with a high rate of systolic heart failure.

Long-Term Survival of Patients With Left Ventricular Noncompaction.

Background The prognosis of left ventricular noncompaction (LVNC) remains elusive despite its recognition as a clinical entity for >30 years. We sought to identify clinical and imaging characteristics and risk factors for mortality in patients with LVNC. Methods and Results 339 adults with LVNC seen between 2000 and 2016 were identified. LVNC was defined as end-systolic noncompacted to compacted myocardial ratio >2 (Jenni criteria) and end-diastolic trough of trabeculation-to-epicardium (X):peak of trabeculation-to-epicardium (Y) ratio <0.5 (Chin criteria) by echocardiography; and end-diastolic noncompacted:compacted ratio >2.3 (Petersen criteria) by magnetic resonance imaging. Median age was 47.4 years, and 46% of patients were female. Left ventricular ejection fraction <50% was present in 57% of patients and isolated apical noncompaction in 48%. During a median follow-up of 6.3 years, 59 patients died. On multivariable Cox regression analysis, age (hazard ratio [HR] 1.04; 95% CI, 1.02-1.06), left ventricular ejection fraction <50% (HR, 2.37; 95% CI, 1.17-4.80), and noncompaction extending from the apex to the mid or basal segments (HR, 2.11; 95% CI, 1.21-3.68) were associated with all-cause mortality. Compared with the expected survival for age- and sex-matched US population, patients with LVNC had reduced overall survival (P<0.001). However, patients with LVNC with preserved left ventricular ejection fraction and patients with isolated apical noncompaction had similar survival to the general population. Conclusions Overall survival is reduced in patients with LVNC compared with the expected survival of age- and sex-matched US population. However, survival rate in those with preserved left ventricular ejection fraction and isolated apical noncompaction was comparable with that of the general population.

Experience With Cardiology-Oriented Outcomes in Critically Ill Patients With Coronavirus Disease 2019.

OBJECTIVES: Coronavirus disease 2019 is associated with high mortality rates and multiple organ damage. There is increasing evidence that these patients are at risk for various cardiovascular insults; however, there are currently no guidelines for the diagnosis and management of such cardiovascular complications in patients with coronavirus disease 2019. We share data and recommendations from a multidisciplinary team to highlight our institution's clinical experiences and guidelines for managing cardiovascular complications of coronavirus disease 2019. DESIGN SETTING AND PATIENTS: This was a retrospective cohort study of patients admitted to one of six ICUs dedicated to the care of patients with coronavirus disease 2019 located in three hospitals within one academic medical center in Atlanta, Georgia. MEASUREMENTS/INTERVENTIONS: Chart review was conducted for sociodemographic, laboratory, and clinical data. Rates of specific cardiovascular complications were assessed, and data were analyzed using a chi-square or Wilcoxon rank-sum test for categorical and continuous variables. Additionally, certain cases are presented to demonstrate the sub committee's recommendations. MAIN RESULTS: Two-hundred eighty-eight patients were admitted to the ICU with coronavirus disease 2019. Of these, 86 died (29.9%), 242 (84.03%) had troponin elevation, 70 (24.31%) had dysrhythmias, four (1.39%) had ST-elevation myocardial infarction, eight (2.78%) developed cor pulmonale, and 190 (65.97%) with shock. There was increased mortality risk in patients with greater degrees of troponin elevation (p < 0.001) and with the development of arrhythmias (p < 0.001), cor pulmonale (p < 0.001), and shock (p < 0.001). CONCLUSIONS: While there are guidelines for the diagnosis and management of pulmonary complications of coronavirus disease 2019, there needs to be more information regarding the management of cardiovascular complications as well. These recommendations garnered from the coronavirus disease 2019 cardiology subcommittee from our institution will add to the existing knowledge of these potential cardiovascular insults as well as highlight suggestions for the diagnosis and management of the range of cardiovascular complications of coronavirus disease 2019. Additionally, with the spread of coronavirus disease 2019, our case-based recommendations provide a bedside resource for providers newly caring for patients with coronavirus disease 2019.