Genetic Testing Practices and Pathological Assessments in End Stage Heart Failure Patients Undergoing Heart Transplantation and Left Ventricular Assist Device.

BACKGROUND: Genetic cardiomyopathies (CM) are increasingly recognized as causes of end-stage heart failure (ESHF). Identification of a genetic etiology in ESHF has important prognostic and family implications. However, genetic testing practices are understudied in ESHF patients. METHODS: This single-center, retrospective study included consecutive ESHF patients who underwent heart transplantation (HT) or left ventricular assist device (LVAD) from 2018 to 2023. Data, including genetic testing and pathology reports, were collected from the electronic medical record. Analyses of demographic and clinical characteristics were stratified by genetic testing completion and presence of clinically actionable variant. Logistic regression was performed to evaluate for associations between histology findings and genetic variants. RESULTS: A total of 529 adult patients (mean age 57 years) were included in the study and were predominantly male (79%, 422/529) and non-white (61%, 322/529). Genetic testing was performed in 54% (196/360) of patients with either non-ischemic or mixed CM. A clinically actionable result was identified in 36% (70/196) of patients, of which, only 43% (30/70) had a genetic counselor referral. The most common genetic variants were TTN (32%, 24/75), MYBPC3 (13%, 10/75), and TTR (11%, 8/75). Clinically actionable variants were identified in patients with known heart failure precipitators, such as alcohol use. In multivariable analysis, presence of interstitial fibrosis, specifically diffuse, on pathology was significantly associated with a clinically actionable variant (aOR 2.29, 95% CI [1.08-4.86], p = 0.03). CONCLUSION: ESHF patients with non-ischemic or mixed CM undergoing advanced therapies had a low uptake of genetic services, including testing and counselors, despite a high burden of genetic disease. Pathology findings, such as interstitial fibrosis, may provide insight into genetic etiology. The underutilization of services suggests a need for implementation strategies to improve uptake.

Heart transplantation from donation after circulatory death: Impact on waitlist time and transplant rate.

The effect of using donation after circulatory death (DCD) hearts on waitlist outcomes has not been substantiated. We retrospectively analyzed 184 heart transplant (HT) candidates at our institution from 2019 to 2021. Patients were stratified into 2 observation periods centered on September 12, 2020, when the adult DCD HT program officially began. The primary outcome was a comparison of transplant rate between period 1 (pre-DCD) and period 2 (post-DCD). Secondary outcomes included waitlist time-to-transplant, waitlist mortality rate, independent predictors of incidence of HT, and posttransplant outcomes. A total of 165 HTs (n = 92 in period 1 and n = 73 in period 2) were performed. The median waitlist time-to-transplant decreased from 47.5 to 19 days in periods 1 and 2, respectively (P = .004). The transplant rate increased from 181 per 100 patient-years in period 1 to 579 per 100 patient-years in period 2 (incidence rate ratio, 1.87; 95% CI, 1.04-3.38; P = .038). There were no statistical differences in waitlist mortality rate (P = .566) and 1-year survival (P = .699) between the 2 periods. DCD HTs (n = 36) contributed to 49.3% of overall HT activity in period 2. We concluded that utilization of DCD hearts significantly reduced waitlist time and increased transplant rate. Short-term posttransplant outcomes were comparable between the pre-DCD and post-DCD periods.

Cardiac Transplantation in Danon Disease.

BACKGROUND: Danon disease (DD) is a rare X-linked dominant cardioskeletal myopathy caused by mutations in the lysosome-associated membrane protein-2 (LAMP-2) gene that is usually lethal without cardiac transplantation. The purpose of this study was to characterize post-transplant outcomes in a large cohort of patients with DD who underwent cardiac transplantation. METHODS: The clinical phenotype and outcome data of patients with DD who underwent cardiac transplantation (n = 38; 19 males and 19 females) were obtained from 8 centers. Study outcomes included graft survival, defined as death or retransplantation, and episodes of acute cellular and antibody-mediated rejection and cardiac allograft vasculopathy at 1 year. RESULTS: Median follow-up time after transplantation for the entire cohort was 4.4 years (IQR: 1.5-12.8 years). The median age at transplant for the cohort was 20.2 years (15.8-27.9 years), with no difference in age between sexes. Median pretransplant left-ventricular ejection fraction for the entire cohort was 30% (range 11%-84%). Males had higher pretransplant aspartate aminotransferase, alanine aminotransferase and creatine phosphokinase levels than females (P < 0.001). There were 2 deaths in the entire cohort and 2 retransplants. There was no difference in actuarial graft survival between males and females (P = 0.8965); the estimated graft survival was 87.1% (95%CI: 63.6%-95.9%) at 5 years. One episode (2.7%) of antibody-mediated rejection, grade 2, and 7 episodes (19%) of acute cellular rejection, grade 2 or 3, were reported in patients who survived to discharge (6 females and 1 male; P = 0.172). CONCLUSIONS: Heart transplantation outcomes are acceptable in DD with high probabilities of 5-year graft survival for males and females suggesting that cardiac transplantation is an effective treatment option for DD patients.

A Review of the Role of Breast Arterial Calcification for Cardiovascular Risk Stratification in Women.

Cardiovascular disease continues to be the leading cause of death among women in the United States. One of the barriers to improving cardiovascular disease outcomes in women is the lack of reliable, effective screening modalities. Breast arterial calcification has emerged as a potential risk stratification tool. Localized deposition in the media of the artery, known as Mönckeberg medial calcific sclerosis, is notably different from the intimal atherosclerotic process commonly associated with coronary artery disease. Nonetheless, studies favor a correlation between breast arterial calcification and cardiovascular risk factors or coronary artery disease, defined as coronary artery calcification on computed tomography scan or both nonobstructive and obstructive lesions on angiography. Since a majority of women over the age of 40 undergo yearly breast cancer screening with mammography, measurement of breast arterial calcification may offer a personalized, noninvasive approach to risk-stratify women for cardiovascular disease at no additional cost or radiation. Mammography has the potential to alter the course of the leading cause of death in women, heart disease, through the evaluation of breast arterial calcification and identification of opportunities for prevention. Current evidence supports the universal reporting of breast arterial calcifications and personalized patient-provider discussions to more aggressively treat cardiac risk factors through targeted medical therapies or healthy lifestyle changes.

Systems Analysis of the Human Pulmonary Arterial Hypertension Lung Transcriptome.

Pulmonary arterial hypertension (PAH) is characterized by increased pulmonary artery pressure and vascular resistance, typically leading to right heart failure and death. Current therapies improve quality of life of the patients but have a modest effect on long-term survival. A detailed transcriptomics and systems biology view of the PAH lung is expected to provide new testable hypotheses for exploring novel treatments. We completed transcriptomics analysis of PAH and control lung tissue to develop disease-specific and clinical data/tissue pathology gene expression classifiers from expression datasets. Gene expression data were integrated into pathway analyses. Gene expression microarray data were collected from 58 PAH and 25 control lung tissues. The strength of the dataset and its derived disease classifier was validated using multiple approaches. Pathways and upstream regulators analyses was completed with standard and novel graphical approaches. The PAH lung dataset identified expression patterns specific to PAH subtypes, clinical parameters, and lung pathology variables. Pathway analyses indicate the important global role of TNF and transforming growth factor signaling pathways. In addition, novel upstream regulators and insight into the cellular and innate immune responses driving PAH were identified. Finally, WNT-signaling pathways may be a major determinant underlying the observed sex differences in PAH. This study provides a transcriptional framework for the PAH-diseased lung, supported by previously reported findings, and will be a valuable resource to the PAH research community. Our investigation revealed novel potential targets and pathways amenable to further study in a variety of experimental systems.

Approach to Lynch Syndrome for the Gastroenterologist.

Lynch syndrome is an autosomal-dominant hereditary cancer syndrome. Mutations in mismatch repair genes, including MLH1, MSH2, MSH6, and PMS2, are implicated in the pathogenesis of the syndrome through microsatellite instability (MSI) and a rapid adenoma-carcinoma sequence. The primary methodologies for diagnosis include clinical criteria (Amsterdam I/II, Revised Bethesda Guidelines), computational models, and genetic testing (MSI, immunohistochemistry, germline testing). Universal genetic testing of colorectal cancers has gained popularity as a method to identify high-risk individuals and to offer appropriate cancer surveillance, psychological reassurance, and family planning. Management includes short-interval surveillance with colonoscopy in those without colorectal cancer and colectomy for those with cancer. Long-term chemoprevention with aspirin may improve mortality.

Natural history and clinical outcomes of patients with hypertrophic cardiomyopathy from thin filament mutations.

Hypertrophic cardiomyopathy (HCM) due to thick filament variants is more common; however, HCM due to thin filament variants (HCM-Thin) may be associated with a more malignant phenotype with an increased risk of sudden cardiac death. The aim of this study was to review all the published cases of HCM-Thin to better understand the natural history and clinical outcomes of this disease. A literature review of HCM-Thin identified 21 studies with a total of 177 patients that were suitable for analysis. There were three outcomes of interest, which included a heart failure composite, a ventricular arrhythmia composite and a heart failure and arrhythmia composite outcome. Kaplan-Meier (KM) survival analyses for freedom from each of the abovementioned composite outcomes were completed for the entire cohort and stratified by age of onset and sarcomeric variant. The heart failure composite occurred in 24 (13.6%) patients, the ventricular arrhythmia composite occurred in 30 patients (16.9%) and the combined heart failure and arrhythmia composite occurred in 50 patients (28.2%). In regard to left ventricular ejection fraction (LVEF), the majority of patients were preserved (LVEF > 50%) compared with mildly reduced (LVEF 41%-50%) and reduced (LVEF ≤ 40%) (respectively 26.6% vs. 0.6% vs. 3.4%). The median maximal left ventricular wall thickness (LVWT) was 19.0 mm [interquartile range (IQR) 5.3]. Only 10.7% of the cohort had evidence of left ventricular outflow tract (LVOT) obstruction. Those with paediatric-onset HCM had earlier onset and were at higher risk for each endpoint than their adult counterparts. When stratified by genetic variant, patients with TNNI3 and TPM1 were at a higher risk of the heart failure composite endpoint and the combined heart failure and arrhythmia composite endpoint in comparison with those with the other genetic variants. HCM-Thin is associated with significant morbidity and mortality, with a high arrhythmia burden despite low rates of cardiac obstruction and mild hypertrophy. The paediatric onset of disease and certain sarcomeric variants appear to be associated with a worse prognosis than their adult-onset and other sarcomeric variant counterparts. HCM-Thin seems to have a distinct phenotype, which may require a different management approach.

Automated Breast Arterial Calcification Score Is Associated With Cardiovascular Outcomes and Mortality.

Background: Breast arterial calcification (BAC) on mammograms has emerged as a biomarker of women's cardiovascular disease (CVD) risk, but there is a lack of quantification tools and clinical outcomes studies. Objectives: This study assessed the association of BAC (both presence and quantity) with CVD outcomes. Methods: This single-center, retrospective study included women with a screening mammogram from 2007 to 2016. BAC was quantified using an artificial intelligence-generated score, which was assessed as both a binary and continuous variable. Regression analyses evaluated the association between BAC and mortality and a composite of acute myocardial infarction, heart failure, stroke, and mortality. Analyses were adjusted for age, race, diabetes, smoking, blood pressure, cholesterol, and history of CVD and chronic kidney disease. Results: A total of 18,092 women were included in this study (mean age 56.8 ± 11.0 years; diabetes [13%], hypertension [36%], hyperlipidemia [40%], and smoking [5%]). BAC was present in 4,223 (23%). Over a median follow-up of 6 years, death occurred in 7.8% and 2.3% of women with and without BAC, respectively. The composite occurred in 12.4% and 4.3% of women with and without BAC, respectively. Compared to those without, women with BAC had adjusted HRs of 1.49 (95% CI: 1.33-1.67) for mortality and 1.56 (95% CI: 1.41-1.72) for the composite. Each 10-point increase in the BAC score was associated with higher risk of mortality (HR: 1.08 [95% CI: 1.06-1.11]) and the composite (HR: 1.08 [95% CI: 1.06-1.10]). BAC was especially predictive of future events among younger women. Conclusions: BAC is independently associated with mortality and CVD, especially among younger women. Measurement of BAC beyond presence adds incremental risk stratification. Quantifying BAC using an artificial intelligence algorithm is feasible, clinically relevant, and may improve personalized CVD risk stratification.

Interfacial electric field effects on a carbene reaction catalyzed by Rh porphyrins.

An intramolecular reaction catalyzed by Rh porphyrins was studied in the presence of interfacial electric fields. 1-Diazo-3,3-dimethyl-5-phenylhex-5-en-2-one (2) reacts with Rh porphyrins via a putative carbenoid intermediate to form cyclopropanation product 3,3-dimethyl-5-phenylbicyclo[3.1.0]hexan-2-one (3) and insertion product 3,3-dimethyl-2,3-dihydro-[1,1'-biphenyl]-4(1H)-one (4). To study this reaction in the presence of an interfacial electric field, Si electrodes coated with thin films of insulating dielectric layers were used as the opposing walls of a reaction vessel, and Rh porphyrin catalysts were localized to the dielectric-electrolyte interface. The charge density was varied at the interface by changing the voltage across the two electrodes. The product ratio was analyzed as a function of the applied voltage and the surface chemistry of the dielectric layer. In the absence of an applied voltage, the ratio of 3:4 was approximately 10:1. With a TiO2 surface, application of a voltage induced a Rh porphyrin-TiO2 interaction that resulted in an increase in the 3:4 ratio to a maximum in which 4 was nearly completely suppressed (>100:1). With an Al2O3 surface or an alkylphosphonate-coated surface, the voltage caused a decrease in the 3:4 ratio, with a maximum effect of lowering the ratio to 1:2. The voltage-induced decrease in the 3:4 ratio in the absence of TiO2 was consistent with a field-dipole effect that changed the difference in activation energies for the product-determining step to favor product 4. Effects were observed for porphyrin catalysts localized to the electrode-electrolyte interface either through covalent attachment or surface adsorption, enabling the selectivity to be controlled with unfunctionalized Rh porphyrins. The magnitude of the selectivity change was limited by the maximum interfacial charge density that could be attained before dielectric breakdown.

The Genetic Evaluation of Dilated Cardiomyopathy.

Dilated cardiomyopathy (DCM) is a common cause of heart failure and is the primary indication for heart transplantation. A genetic etiology can be found in 20-35% of patients with DCM, especially in those with a family history of cardiomyopathy or sudden cardiac death at an early age. With advancements in genome sequencing, the understanding of genotype-phenotype relationships in DCM has expanded with over 60 genes implicated in the disease. Subsequently, these findings have increased adoption of genetic testing in the management of DCM, which has allowed for improved risk stratification and identification of at risk family members. In this review, we discuss the genetic evaluation of DCM with a focus on practical genetic testing considerations, genotype-phenotype associations, and insights into upcoming personalized therapies.

Thin filament cardiomyopathies: A review of genetics, disease mechanisms, and emerging therapeutics.

All muscle contraction occurs due to the cyclical interaction between sarcomeric thin and thick filament proteins within the myocyte. The thin filament consists of the proteins actin, tropomyosin, Troponin C, Troponin I, and Troponin T. Mutations in these proteins can result in various forms of cardiomyopathy, including hypertrophic, restrictive, and dilated phenotypes and account for as many as 30% of all cases of inherited cardiomyopathy. There is significant evidence that thin filament mutations contribute to dysregulation of Ca2+ within the sarcomere and may have a distinct pathomechanism of disease from cardiomyopathy associated with thick filament mutations. A number of distinct clinical findings appear to be correlated with thin-filament mutations: greater degrees of restrictive cardiomyopathy and relatively less left ventricular (LV) hypertrophy and LV outflow tract obstruction than that seen with thick filament mutations, increased morbidity associated with heart failure, increased arrhythmia burden and potentially higher mortality. Most therapies that improve outcomes in heart failure blunt the neurohormonal pathways involved in cardiac remodeling, while most therapies for hypertrophic cardiomyopathy involve use of negative inotropes to reduce LV hypertrophy or septal reduction therapies to reduce LV outflow tract obstruction. None of these therapies directly address the underlying sarcomeric dysfunction associated with thin-filament mutations. With mounting evidence that thin filament cardiomyopathies occur through a distinct mechanism, there is need for therapies targeting the unique, underlying mechanisms tailored for each patient depending on a given mutation.

Nocturnal Respiratory Rate Dynamics Enable Early Recognition of Impending Hospitalizations.

The days and weeks preceding hospitalization are poorly understood because they transpire before patients are seen in conventional clinical care settings. Home health sensors offer opportunities to learn signatures of impending hospitalizations and facilitate early interventions, however the relevant biomarkers are unknown. Nocturnal respiratory rate (NRR) is an activity-independent biomarker that can be measured by adherence-independent sensors in the home bed. Here, we report automated longitudinal monitoring of NRR dynamics in a cohort of high-risk recently hospitalized patients using non-contact mechanical sensors under patients' home beds. Since the distribution of nocturnal respiratory rates in populations is not well defined, we first quantified it in 2,000 overnight sleep studies from the NHLBI Sleep Heart Health Study. This revealed that interpatient variability was significantly greater than intrapatient variability (NRR variances of 11.7 brpm2 and 5.2 brpm2 respectively, n=1,844,110 epochs), which motivated the use of patient-specific references when monitoring longitudinally. We then performed adherence-independent longitudinal monitoring in the home beds of 34 high-risk patients and collected raw waveforms (sampled at 80 Hz) and derived quantitative NRR statistics and dynamics across 3,403 patient-nights (n= 4,326,167 epochs). We observed 23 hospitalizations for diverse causes (a 30-day hospitalization rate of 20%). Hospitalized patients had significantly greater NRR deviations from baseline compared to those who were not hospitalized (NRR variances of 3.78 brpm2 and 0.84 brpm2 respectively, n= 2,920 nights). These deviations were concentrated prior to the clinical event, suggesting that NRR can identify impending hospitalizations. We analyzed alarm threshold tradeoffs and demonstrated that nominal values would detect 11 of the 23 clinical events while only alarming 2 times in non-hospitalized patients. Taken together, our data demonstrate that NRR dynamics change days to weeks in advance of hospitalizations, with longer prodromes associating with volume overload and heart failure, and shorter prodromes associating with acute infections (pneumonia, septic shock, and covid-19), inflammation (diverticulitis), and GI bleeding. In summary, adherence-independent longitudinal NRR monitoring has potential to facilitate early recognition and management of pre-symptomatic disease.

A case report of cardiogenic shock from takotsubo cardiomyopathy with left ventricular outflow tract obstruction: fundamental lessons in cardiac pathophysiology.

BACKGROUND: A subset of patients with takotsubo cardiomyopathy will develop significant dynamic left ventricular outflow tract (LVOT) obstruction leading to cardiogenic shock. However, traditional therapies for cardiogenic shock that focus on increased inotropy and afterload reduction can be detrimental in this situation. CASE SUMMARY: We describe a 71-year-old woman who presented to the emergency department with typical, substernal chest pain found to be hypotensive with ST-elevations in the lateral leads. Coronary angiography showed no significant coronary artery disease, but a left ventriculogram demonstrated takotsubo cardiomyopathy. Right heart catheterization revealed cardiogenic shock and elevated filling pressures. Haemodynamics and symptoms worsened with the initiation of dopamine and placement of intra-aortic balloon pump but improved with the initiation of phenylephrine. Follow-up echocardiogram demonstrated dynamic LVOT obstruction with concomitant severe mitral regurgitation (MR). The patient recovered in the intensive care unit for 5 days after successful weaning of phenylephrine and initiation of low-dose beta-blocker. Repeat echocardiogram 3 weeks later showed complete resolution of apical akinesis, LVOT obstruction, and MR. DISCUSSION: Elucidating whether dynamic LVOT obstruction is contributing to cardiogenic shock physiology is paramount since the management radically differs depending on the presence or absence of obstruction. Corrective therapy focuses on reducing the LVOT gradient and includes fluid administration to improve preload, beta-blocker therapy to increase diastolic filling time, and vasopressors to raise afterload.

Subclinical left ventricular dysfunction in COVID-19.

BACKGROUND: Coronavirus Disease-2019 (COVID-19) is associated with cardiovascular injury, but left ventricular (LV) function is largely preserved. We aimed to evaluate for subclinical LV dysfunction in patients with COVID-19 through myocardial strain analysis. METHODS: We performed a single-center retrospective cohort study of all patients hospitalized with COVID-19 who underwent echocardiography. Traditional echocardiographic and global longitudinal strain (GLS) values were compared with prior and subsequent echocardiograms. RESULTS: Among 96 patients hospitalized with COVID-19 with complete echocardiograms, 67 (70%) had adequate image quality for strain analysis. The cohort was predominantly male (63%) and 18% had prevalent cardiovascular disease (CVD). Echocardiograms were largely normal with median [IQR] LV ejection fraction (EF) 62% [56%, 68%]. However, median GLS was abnormal in 91% (-13.5% [-15.0%, -10.8%]). When stratified by CVD, both groups had abnormal GLS, but presence of CVD was associated with worse median GLS (-11.6% [-13.4%, -7.2%] vs -13.9% [-15.0%, -11.3%], p = 0.03). There was no difference in EF or GLS when stratified by symptoms or need for intensive care. Compared to pre-COVID-19 echocardiograms, EF was unchanged, but median GLS was significantly worse (-15% [-16%, -14%] vs -12% [-14%, -10%], p = 0.003). Serial echocardiograms showed no significant changes in GLS or EF overall, however patients who died had stable or worsening GLS, while those who survived to discharge home showed improved GLS. CONCLUSIONS: Patients with COVID-19 had evidence of subclinical cardiac dysfunction manifested by reduced GLS despite preserved EF. These findings were observed regardless of history of CVD, presence of COVID-19 symptoms, or severity of illness.

Passive longitudinal weight and cardiopulmonary monitoring in the home bed.

Home health monitoring has the potential to improve outpatient management of chronic cardiopulmonary diseases such as heart failure. However, it is often limited by the need for adherence to self-measurement, charging and self-application of wearables, or usage of apps. Here, we describe a non-contact, adherence-independent sensor, that when placed beneath the legs of a patient's home bed, longitudinally monitors total body weight, detailed respiratory signals, and ballistocardiograms for months, without requiring any active patient participation. Accompanying algorithms separate weight and respiratory signals when the bed is shared by a partner or a pet. Validation studies demonstrate quantitative equivalence to commercial sensors during overnight sleep studies. The feasibility of detecting obstructive and central apneas, cardiopulmonary coupling, and the hemodynamic consequences of non-sustained ventricular tachycardia is also established. Real-world durability is demonstrated by 3 months of in-home monitoring in an example patient with heart failure and ischemic cardiomyopathy as he recovers from coronary artery bypass grafting surgery. BedScales is the first sensor to measure adherence-independent total body weight as well as longitudinal cardiopulmonary physiology. As such, it has the potential to create a multidimensional picture of chronic disease, learn signatures of impending hospitalization, and enable optimization of care in the home.

Relation of prior statin and anti-hypertensive use to severity of disease among patients hospitalized with COVID-19: Findings from the American Heart Association's COVID-19 Cardiovascular Disease Registry.

BACKGROUND: Statins have anti-inflammatory and immunomodulatory effects that may reduce the severity of coronavirus disease 2019 (COVID-19), in which organ dysfunction is mediated by severe inflammation. Large studies with diverse populations evaluating statin use and outcomes in COVID-19 are lacking. METHODS AND RESULTS: We used data from 10,541 patients hospitalized with COVID-19 through September 2020 at 104 US hospitals enrolled in the American Heart Association's COVID-19 Cardiovascular Disease (CVD) Registry to evaluate the associations between statin use and outcomes. Prior to admission, 42% of subjects (n = 4,449) used statins (7% on statins alone, 35% on statins plus anti-hypertensives). Death (or discharge to hospice) occurred in 2,212 subjects (21%). Outpatient use of statins, either alone or with anti-hypertensives, was associated with a reduced risk of death (adjusted odds ratio [aOR] 0.59, 95% CI 0.50-0.69), adjusting for demographic characteristics, insurance status, hospital site, and concurrent medications by logistic regression. In propensity-matched analyses, use of statins and/or anti-hypertensives was associated with a reduced risk of death among those with a history of CVD and/or hypertension (aOR 0.68, 95% CI 0.58-0.81). An observed 16% reduction in odds of death among those without CVD and/or hypertension was not statistically significant. CONCLUSIONS: Patients taking statins prior to hospitalization for COVID-19 had substantially lower odds of death, primarily among individuals with a history of CVD and/or hypertension. These observations support the continuation and aggressive initiation of statin and anti-hypertensive therapies among patients at risk for COVID-19, if these treatments are indicated based upon underlying medical conditions.

Myocardial Strain and Association With Clinical Outcomes in Danon Disease: A Model for Monitoring Progression of Genetic Cardiomyopathies.

Background Myocardial strain can identify subclinical left ventricular dysfunction in various cardiac diseases, but its association with clinical outcomes in genetic cardiomyopathies remains unknown. Herein, we assessed myocardial strain in patients with Danon disease (DD), a rare X-linked autophagic disorder that causes severe cardiac manifestations. Methods and Results Echocardiographic images were reviewed and used to calculate myocardial strain from a retrospective, international registry of patients with DD. Regression analyses were performed to evaluate for an association of global longitudinal strain (GLS) and ejection fraction with the composite outcome (death, ventricular assist device, heart transplantation, and implantable cardioverter defibrillator for secondary prevention). A total of 22 patients with DD (male 14 [63.6%], median age 16.5 years) had sufficient echocardiograms for analysis. Absolute GLS was reduced with a mean of 12.2% with an apical-sparing pattern observed. Univariable regression for GLS and composite outcome showed an odds ratio of 1.32 (95% CI, 1.02-1.71) with P=0.03. For receiver operating characteristic analysis, the areas under the curve for GLS and ejection fraction were 0.810 (P=0.02) and 0.605 (P=0.44), respectively. An absolute GLS cutoff of 10.0% yielded a true positive rate of 85.7% and false positive rate of 13.3%. Conclusions In this cohort of patients with DD, GLS may be a useful assessment of myocardial function and may predict clinical outcomes. This study highlights the potential use of myocardial strain phenotyping to monitor disease progression and potentially to predict clinical outcomes in DD and other genetic cardiomyopathies.

Outcome of patients on heart transplant list treated with a continuous-flow left ventricular assist device: Insights from the TRans-Atlantic registry on VAd and TrAnsplant (TRAViATA).

BACKGROUND: Geographic variations in management and outcomes of individuals supported by continuous-flow left ventricular assist devices (CF-LVAD) between the United States (US) and Europe (EU) is largely unknown. METHODS: We created a retrospective, multinational registry of 524 patients who received a CF-LVAD (either HVAD or Heartmate II) between January 2008 and April 2017. Follow up spanned from date of CF-LVAD implant to post-HTx period with a median follow up of 44.8 months. RESULTS: The cohort included 299 (57.1%) EU and 225 (42.9%) US patients. Although the US cohort was significantly older with a higher prevalence of comorbidities, survival was similar between the cohorts (US 63.1%, EU 68.4% at 5 years, unadjusted log-rank test p = 0.43).Multivariate analyses suggested that older age, higher body mass index, elevated creatinine, use of temporary mechanical circulatory support prior CF-LVAD, and implantation of HVAD were associated with increased mortality. Among CF-LVAD patients undergoing HTx, the median time on CF-LVAD support was shorter in the US, meanwhile US donors were younger. Finally, the pattern of adverse events (stroke, gastrointestinal bleedings, late right ventricular failure, and driveline infection) during support differed significantly between US and EU. CONCLUSIONS: Although waitlisted patients in the US on CF-LVAD have higher risk comorbid conditions, the overall outcome is similar in US and EU. Geographic variations with regards to donor characteristics, duration of CF-LVAD support prior to transplant, and adverse events on support can explain the disparity in the utilization of mechanical bridge to transplant strategy between US and EU.

Relation of Statin Use Prior to Admission to Severity and Recovery Among COVID-19 Inpatients.

The impact of statins, angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers (ARBs) on coronavirus disease 2019 (COVID-19) severity and recovery is important given their high prevalence of use among individuals at risk for severe COVID-19. We studied the association between use of statin/angiotensin-converting enzyme inhibitors/ARB in the month before hospital admission, with risk of severe outcome, and with time to severe outcome or disease recovery, among patients hospitalized for COVID-19. We performed a retrospective single-center study of all patients hospitalized at University of California San Diego Health between February 10, 2020 and June 17, 2020 (n = 170 hospitalized for COVID-19, n = 5,281 COVID-negative controls). Logistic regression and competing risks analyses were used to investigate progression to severe disease (death or intensive care unit admission), and time to discharge without severe disease. Severe disease occurred in 53% of COVID-positive inpatients. Median time from hospitalization to severe disease was 2 days; median time to recovery was 7 days. Statin use prior to admission was associated with reduced risk of severe COVID-19 (adjusted OR 0.29, 95%CI 0.11 to 0.71, p < 0.01) and faster time to recovery among those without severe disease (adjusted HR for recovery 2.69, 95%CI 1.36 to 5.33, p < 0.01). The association between statin use and severe disease was smaller in the COVID-negative cohort (p for interaction = 0.07). There was potential evidence of faster time to recovery with ARB use (adjusted HR 1.92, 95%CI 0.81 to 4.56). In conclusion, statin use during the 30 days prior to admission for COVID-19 was associated with a lower risk of developing severe COVID-19, and a faster time to recovery among patients without severe disease.