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Aims There are no comprehensive machine learning (ML) tools used by oncologists to assist with risk identification and referrals to cardio-oncology. This study applies ML algorithms to identify oncology patients at risk for cardiovascular disease for referrals to cardio-oncology and to generate risk scores to support quality of care. Methods and results De-identified patient data were obtained from Vanderbilt University Medical Center. Patients with breast, kidney, and B-cell lymphoma cancers were targeted. Additionally, the study included patients who received immunotherapy drugs for treatment of melanoma, lung cancer, or kidney cancer. Random forest (RF) and artificial neural network (ANN) ML models were applied to analyse each cohort: A total of 20 023 records were analysed (breast cancer, 6299; B-cell lymphoma, 9227; kidney cancer, 2047; and immunotherapy for three covered cancers, 2450). Data were divided randomly into training (80%) and test (20%) data sets. Random forest and ANN performed over 90% for accuracy and area under the curve (AUC). All ANN models performed better than RF models and produced accurate referrals. Conclusion Predictive models are ready for translation into oncology practice to identify and care for patients who are at risk of cardiovascular disease. The models are being integrated with electronic health record application as a report of patients who should be referred to cardio-oncology for monitoring and/or tailored treatments. Models operationally support cardio-oncology practice. Limited validation identified 86% of the lymphoma and 58% of the kidney cancer patients with major risk for cardiotoxicity who were not referred to cardio-oncology.

Bicuspid aortic valve (BAV) is the most common valvular congenital heart disease, with a prevalence of 0.5 to 2% in the general population. Patients with BAV are at risk for developing cardiovascular complications, some of which are life-threatening. BAV has a wide spectrum of clinical presentations, ranging from silent malformation to severe and even fatal cardiac events. Despite the significant burden on both the patients and the health systems, data are limited regarding pathophysiology, risk factors, and genetics. Family studies indicate that BAV is highly heritable, with autosomal dominant inheritance, incomplete penetrance, variable expressivity, and male predominance. Owing to its complex genetic model, including high genetic heterogenicity, only a few genes were identified in association with BAV, while the majority of BAV genetics remains obscure. Here, we review the different forms of BAV and the current data regarding its genetics. Given the clear heritably of BAV with the potential high impact on clinical outcome, the clinical value and cost effectiveness of cascade screening are discussed.

Mitral valve prolapse (MVP) is the most common primary valvular abnormality, associated with various degrees of incompetent function and sequelae, including heart failure and sudden cardiac death. Recent improvements in echocardiographic techniques and new insights into mitral valve anatomy and physiology have rendered the diagnosis of this condition more accurate and reliable. Here we review the genetic etiology, clinical significance, diagnosis, and treatment options for MVP patients.

International audience; Background - Infective endocarditis (IE) is a common and serious complication in patients receiving chronic hemodialysis (HD). Objectives - This study sought to investigate whether there are significant differences in complications, cardiac surgery, relapses, and mortality between IE cases in HD and non-HD patients. Methods - Prospective cohort study (International Collaboration on Endocarditis databases, encompassing 7,715 IE episodes from 2000 to 2006 and from 2008 to 2012). Descriptive analysis of baseline characteristics, epidemiological and etiological features, complications and outcomes, and their comparison between HD and non-HD patients was performed. Risk factors for major embolic events, cardiac surgery, relapses, and in-hospital and 6-month mortality were investigated in HD-patients using multivariable logistic regression. Results - A total of 6,691 patients were included and 553 (8.3%) received HD. North America had a higher HD-IE proportion than the other regions. The predominant microorganism was Staphylococcus aureus (47.8%), followed by enterococci (15.4%). Both in-hospital and 6-month mortality were significantly higher in HD versus non-HD-IE patients (30.4% vs. 17% and 39.8% vs. 20.7%, respectively; p

Cancer patients with heart failure (HF) and severe mitral regurgitation (MR) are often considered to be at risk for surgical mitral valve repair/replacement. Severe MR inducing symptomatic HF may prevent delivery of potentially cardiotoxic chemotherapy and complicate fluid management with other cancer treatments.To evaluate the outcome of percutaneous mitral valve repair (PMVR) in oncology patients with HF and significant MR.Our study comprised 145 patients who underwent PMVR, MitraClip, at Hadassah Medical Center between August 2015 and September 2019, including 28 patients who had active or history of cancer. Data from 28 cancer patients were compared to 117 no-cancer patients from the cohort.There was no significant difference in the mean age of cancer patients and no-cancer patients (76 vs. 80 years, P = 0.16); 67% of the patients had secondary (functional) MR. Among cancer patients, 21 had solid tumor and 7 had hematologic malignancies. Nine patients (32%) had active malignancy at the time of PMVR. The mean short-term risk score of the patients was similar in the two groups, as were both 30-day and 1-year mortality rates (7% vs. 4%, P = 0.52) and (29% vs. 16%, P = 0.13), respectively.PMVR in cancer patients is associated with similar 30-day and 1-year survival rate compared with patients without cancer. PMVR should be considered for cancer patients presenting with HF and severe MR and despite their malignancy. This approach may allow cancer patients to safely receive planned oncological treatment.

Transcription factor E3 (TFE3), which is a key regulator of cellular adaptation, is expressed in most tissues, including the heart, and is reportedly overexpressed during cardiac hypertrophy. In this study, TFE3's role in cardiac hypertrophy was investigated. To understand TFE3's physiological importance in cardiac hypertrophy, pressure-overload cardiac hypertrophy was induced through transverse aortic constriction (TAC) in both wild-type (WT) and TFE3 knockout mice (TFE3-/-). Eleven weeks after TAC induction, cardiac hypertrophy was observed in both WT and TFE3-/- mice. However, significant reductions in ejection fraction and fractional shortening were observed in WT mice compared to TFE3-/- mice. To understand the mechanism, we found that myosin heavy chain (Myh7), which increases during hemodynamic overload, was lower in TFE3-/- TAC mice than in WT TAC mice, whereas extracellular signal-regulated protein kinases (ERK) phosphorylation, which confers cardioprotection, was lower in the left ventricles of WT mice than in TFE3-/- mice. We also found high expressions of TFE3, histone, and MYH7 and low expression of pERK in the normal human heart compared to the hypertensive heart. In the H9c2 cell line, we found that ERK inhibition caused TFE3 nuclear localization. In addition, we found that MYH7 was associated with TFE3, and during TFE3 knockdown, MYH7 and histone were downregulated. Therefore, we showed that TFE3 expression was increased in the mouse model of cardiac hypertrophy and tissues from human hypertensive hearts, whereas pERK was decreased reversibly, which suggested that TFE3 is involved in cardiac hypertrophy through TFE3-histone-MYH7-pERK signaling.

Background: The role of the MitraClip implantation in treatment of critically ill patients with heart failure and severe functional mitral regurgitation is undetermined.Methods: We screened...

Purpose Primary sarcoma of the heart is a rare but devastating tumor. Median survival with conventional treatment is 8-12 months. When resection is not feasible, patients often succumb to heart failure secondary to obstruction of blood flow, valve dysfunction, chamber compression or conduction abnormalities. Palliative treatment options include systemic chemotherapy and external beam irradiation. We herein describe a novel technique using endovascular brachytherapy, aiming at reducing tumor mass, alleviating right ventricular pressure overload and at the same time keeping the option of R0 resection viable. Material and methods A 35-year-old man was diagnosed with a non-resectable high-grade intimal sarcoma of the right ventricle (RV), main pulmonary artery (PA) and right PA. After three cycles of doxorubicin and ifosfamide, the patient's symptoms of right heart failure worsened. Imaging documented tumor progression and supra-systemic pulmonary artery pressure. Through a trans-femoral venous access, a brachytherapy sleeve was placed in the RV and main and right PA. A dose of 20 Gy was delivered over a period of ten minutes. Results The patient had an uneventful course and was discharged home 24 hours after the procedure. Ten months after brachytherapy, repeat imaging demonstrated a significant reduction in tumor volume and an increase in pulmonary artery cross-sectional area with a marked reduction of pulmonary artery pressure, leading to a complete resolution of heart failure symptoms. Conclusions Endovascular brachytherapy is a novel, safe and effective therapeutic modality for non-resectable primary cardiac sarcomas either for palliation of obstruction, or tumor mass reduction to allow complete resection.

OBJECTIVES Pleural effusions (PEffs) are known to occur in type B acute aortic dissection (TBAAD). We investigated the relationship between pleural effusion and the development of early or late complications following TBAAD. METHODS The incidence of PEff (defined as at least an obliteration of the costophrenic angle in a frontal projection) diagnosed on their initial chest X-ray in patients with TBAAD enrolled in the International Registry of Acute Aortic Dissection was examined. We analysed in-hospital outcomes and long-term survival separately for patients with and without PEffs (PEff+ versus PEff−, respectively). RESULTS Included were 1252 patients with TBAAD, of whom 224 (17.9%) had PEff. Compared with patients without PEff in the initial chest X-ray, these were significantly older [mean age 67 (SD: 14.7) vs 63.4 (SD: 14.2) years, P = 0.001] and more often female (42.4% vs 34.2%, P = 0.021) and had more comorbidities (known aortic aneurysm, chronic obstructive pulmonary disease, chronic renal failure, diabetes, congestive heart failure or mitral valve disease). PEff was associated with higher in-hospital mortality (16.1% vs 9.1%, P = 0.002) and increased rates of neurological complications (16.6% vs 11.1%, P = 0.029), acute renal failure (27.2% vs 19.7%, P = 0.017) and hypotension (17.4% vs 9.6%, P = 0.001). In addition, patients with PEff underwent aortic repair more frequently (44.6% vs 32.5%, P CONCLUSIONS Patients with TBAAD and evidence of PEff showed a higher in-hospital mortality, are more likely to develop additional in-hospital complications and have a decreased likelihood of survival during follow-up. However, according to propensity-matched analysis, PEff remained not as an independent predictor of worse outcome but might serve as an early surrogate marker to identify higher-risk patients.

Introduction Bicuspid aortic valve (BAV) is the commonest congenital heart valve defect, found in 1% to 2% of the general population and associated with life-threatening complications. Given the high heritability index of BAV, many experts recommend echocardiography for first-degree relatives (FDRs) of an index patient. However, the cost-effectiveness of such cascade screening for BAV has not been fully evaluated. Materials and methods Using a decision-analytic model, we performed a cost-effectiveness analysis of echocardiographic screening of FDRs of BAV index cases. Data on BAV probabilities and BAV complications among FDRs were derived from our institution's BAV familial cohort and from the relevant literature on population-based BAV cohorts with long-term follow-up. Health gain was measured as quality-adjusted life years (QALYs). Cost inputs were based on list prices and literature data. One-way and probabilistic sensitivity analyses were performed to account for uncertainty in the model's variables. Results and disscusion Screening of FDRs was found to be the dominant strategy, being more effective and less costly than no screening, with savings of €208 and gains of 1.6 QALYs. Results were sensitive to the full range of reported BAV rates among FDRs across the literature, with the benefit gradually decreasing from the screening age of 55 years, with trend shifting at the age of 69. Conclusions This economic evaluation model revealed that echocardiographic screening of FDRs of BAV index case is not only clinically important but also highly cost effective and cost-saving. Health gains could be achieved from initiating screening program, along with costs saving. Sensitivity analysis supported the model's robustness, suggesting its generalization. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Center for Interdisciplinary Data Science Research fellowships grant

Contains fulltext : 231547.pdf (Publisher’s version ) (Open Access) With the improvement in survival rate, cardiotoxicity has emerged as a significant adverse effect of cancer therapy. Early diagnosis of subclinical cardiac injury may allow the initiation of cardioprotective therapy and preventing the interruption of optimal cancer therapy and the development of irreversible cardiac dysfunction. In this article, we review the role of two-dimensional speckle tracking echocardiography (2D-STE), beyond the common left ventricle global longitudinal strain in the diagnosis of early subclinical cardiac injury in patients treated with cancer therapies.

Importance Women with aortopathy conditions are at risk for pregnancy-related aortic dissection, and these conditions may not be recognized until after the aortic dissection occurs. Objective To examine the clinical characteristics, imaging features, and outcomes in women with pregnancy-related acute aortic dissection. Design, Setting, and Participants A cohort study, comprising data from the International Registry of Acute Aortic Dissection (IRAD) (February 1, 1998, to February 28, 2018). The multicenter referral center study included 29 women with aortic dissection during pregnancy or less than 12 weeks post partum in IRAD from 1998 to 2018. Main Outcomes and Measures Clinical features of pregnancy-related aortic dissection to be studied included underlying aortopathy, aortic size, type of aortic dissection, timing of dissection, hypertension, and previous aortic surgery. Results A total of 29 women (mean [SD] age, 32 [6] years) had pregnancy-related aortic dissection, representing 0.3% of all aortic dissections and 1% of aortic dissection in women in the IRAD. Among women younger than 35 years, aortic dissection was related to pregnancy in 20 of 105 women (19%). Thirteen women (45%) had type A aortic dissection, and 16 women (55%) had type B. Aortic dissection onset was known in 27 women (93%): 15 during pregnancy, 4 in the first trimester, and 11 in the third trimester; 12 were post partum, occurring a mean (SD) of 12.5 (14) days post partum. At type A aortic dissection diagnosis, the mean (SD) aortic diameters were sinus of Valsalva, 54.5 (5) mm and ascending aorta, 54.7 (6) mm. At type B aortic dissection diagnosis, the mean (SD) descending aortic diameter was 32.5 (5) mm. Twenty women (69%) had an aortopathy condition or a positive family history: 13 women (65%) with Marfan syndrome, 2 women (10%) with Loeys-Dietz syndrome, 2 women (10%) with bicuspid aortic valves, 2 women (10%) with a family history of aortic disease, and 1 woman (5%) with familial thoracic aortic aneurysm. Aortopathy was not recognized until after aortic dissection in 47% of the women. Twenty-eight women (97%) survived aortic dissection hospitalization. Conclusions and Relevance Aortic dissection complicating pregnancy is rare. Most pregnancy-related aortic dissection is due to an aortopathy often not diagnosed until after aortic dissection. In this study, type A aortic dissections were associated with a dilated aorta, and type B aortic dissections often were not. Recognition of underlying conditions and risks for aortic dissection may improve management of pregnancy in women with aortopathy.

Background People over the age of 85 are a rapidly growing age group with a high incidence of congestive heart failure (CHF), in particular heart failure with preserved ejection fraction (HFpEF). The diagnosis of CHF is challenging and longitudinal data assessing cardiac structure and function are necessary to distinguish physiologic from pathologic cardiac aging. The objective of the study was to determine longitudinal changes in cardiac struture and function from ages 85 to 94 years using home echocardiography. Methods Subjects were recruited from the Jerusalem Longitudinal Cohort Study. Sixty three members of the initial cohort (32F, 31M) who underwent home echocardiography at age 85 were the subjects of the current study and underwent repeat home 2-D and Doppler echocardiographic assessment at age 94. Results There were no significant longitudinal changes in left ventricular mass index (LVMI), however LV end-diastolic volume significantly decreased from 113.4 ± 30 to 103.6 ± 35.5 mL (P < 0.02). Ejection fraction (EF) remained stable, however longitudinal systolic function significantly decreased with age from 7.9 ± 1.8 to 6.6 ± 1.4 cm/s2 (P < 0.0001). Diastolic function as assessed by increased E: e' (11.2 ± 3.4 to 16 ± 7.5, P < 0.0001) and increased left atrial volume index (34.1 ± 11.3 to 42.4 ± 13.7 mL/m2, P < 0.0001) was reduced with aging. Conclusions This study demonstrated preserved EF with decreased longitudinal systolic function and diastolic function without significant change in LV mass. Changes in LV function in the very elderly may be independent of changes in LV geometry.

Detection of cardiomyocyte death is crucial for the diagnosis and treatment of heart disease. Here we use comparative methylome analysis to identify genomic loci that are unmethylated specifically in cardiomyocytes, and develop these as biomarkers to quantify cardiomyocyte DNA in circulating cell-free DNA (cfDNA) derived from dying cells. Plasma of healthy individuals contains essentially no cardiomyocyte cfDNA, consistent with minimal cardiac turnover. Patients with acute ST-elevation myocardial infarction show a robust cardiac cfDNA signal that correlates with levels of troponin and creatine phosphokinase (CPK), including the expected elevation-decay dynamics following coronary angioplasty. Patients with sepsis have high cardiac cfDNA concentrations that strongly predict mortality, suggesting a major role of cardiomyocyte death in mortality from sepsis. A cfDNA biomarker for cardiomyocyte death may find utility in diagnosis and monitoring of cardiac pathologies and in the study of normal human cardiac physiology and development., The detection of cardiomyocyte death is a critical aspect in the diagnosis and monitoring of heart diseases. Here the authors show that cardiomyocyte-specific methylation patterns of circulating cell-free DNA may serve as a biomarker of cardiac cell death in infarcted and septic patients.

Between January 1996 and May 2017, the International Registry on Acute Aortic Dissections has collected information on a total of 6,424 consecutive patients with acute aortic dissection, including 258 individuals with a diagnosis of Marfan syndrome. Patients with Marfan syndrome presented at a significantly younger age compared to patients without Marfan syndrome (38.2±13.2 vs. 63.0±14.0 years; P

Type A acute aortic dissection (TAAAD) is conventionally treated with surgery; however, some patients are poor surgical candidates and medical management (MM) is occasionally undertaken. Pre-operative factors influencing survival with MM of TAAAD are unknown. This study utilizes the International

Background Head and neck pain is an atypical presentation of acute aortic dissection. Classic teaching associates this pain with proximal dissections, but this has not been extensively studied. Methods Patients enrolled in the International Registry of Acute Aortic Dissection from January 1996 to March 2015 were included in this study. We analyzed the demographics, presentation, treatment, and outcomes of Type A aortic dissection patients presenting with head and neck pain (n = 812, 25.8%) and compared it with those without these symptoms (n = 2,341, 74.2%). Results Patients with head and neck pain were more likely to be white, female, with a family history of aortic disease. Patients with head and neck pain had higher percentages of back pain (43.3% vs. 37.5%, p = 0.005) and chest pain (87.6% vs. 79.3%, p 65 years were significantly associated with increased mortality. Conclusion Presence of head and neck pain in Type A dissection is associated with more arch involvement, intramural hematoma, and stroke. When isolating those with head and neck pain only, there appear to be a higher rate of comorbidity burden and higher overall mortality.

Objective: Bicuspid aortic valve is a common risk factor for thoracic aortic aneurysm and dissection. Guidelines for elective ascending aortic intervention (AAI) in bicuspid aortic valve are derived from limited evidence, and the extent of practice variation due to patient and provider characteristics is unknown. Using data from 2 large cardiovascular registries, we investigated factors that influence decisions for AAI. Methods: All bicuspid aortic valve cases with known aortic diameters and surgical status were included. We used multivariable logistic regression to profile predictors of isolated aortic valve replacement (AVR) or AVR+AAI, stratified by patient characteristics, surgical indications, and institution. Results: We studied 2861 subjects at 18 institutions from 1996 to 2015. The median aortic diameter of patients who underwent AVR+AAI varied widely across institutions (39-52 mm). Aortic diameters were

Aims We sought to assess the efficacy of a heart valve clinic (HVC) follow-up programme for patients with severe aortic stenosis (AS). Methods and results Three hundred and eighty-eight consecutive patients with AS (age 71 ± 10 years; aortic-jet velocity 5.1 ± 0.6 m/s) and an indication for aortic valve replacement (AVR) were included. Of these, 290 patients presented with an indication for surgery at their first visit at the HVC and 98 asymptomatic patients who had been enrolled in an HVC monitoring programme developed indications for surgery during follow-up. Time to symptom detection was significantly longer in patients that presented with symptoms at baseline (352 ± 471 days) than in patients followed in the HVC (76 ± 75 days, P < 0.001). Despite being educated to recognize and promptly report new symptoms, 77 of the 98 patients in the HVC programme waited until the next scheduled consultation to report them. Severe symptom onset (NYHA or CCS Class ≥III) was present in 61% of patients being symptomatic at the initial visit and in 34% of patients in the HVC programme ( P < 0.001). Conclusion Delays in referral and symptom reporting as well as symptom denial are common in patients with AS. These findings support the concept of risk stratification to identify patients who may benefit from elective surgery. A structured HVC programme results in the detection of symptoms at an earlier and less severe stage and thus in an optimized timing of surgery.

Acute aortic dissection (AoD) during pregnancy or postpartum is rare and is related to aortic wall, hormonal and hemodynamic changes in pregnancy. Women with underlying aortopathy are at increased risk. All women with pregnancy-related AoD enrolled in IRAD from 1998 to 2019 were included. Clinical

Pericardial tamponade (PT) is a devastating complication of Type A acute aortic dissection (TAAAD) that significantly increases the risk of death. We sought to describe the incidence, management, and outcomes of PT in TAAAD. TAAAD patients enrolled in the International Registry of Acute Aortic

During the period of 1986–1997 the first 4 publications on the mechanical and metabolic properties of heat acclimated rat's heart were published. The outcome of these studies implied that heat acclimation, sedentary as well as combined with exercise training, confers long lasting protection against ischemic/reperfusion insult. These results promoted a clinical study on patients with coronary artery disease scheduled for elective coronary artery bypass operations aiming to elucidate whether exploitation of environmental stress can be translated into human benefits by improving physiological recovery. During the 1998 study, immediate-post operative chamber stiffness was assessed in patients acclimatized to heat and low intensity training in the desert (spring in the Dead Sea, 17–33°C) vs. patients in colder weather (spring in non-desert areas, 6–19°C) via echocardiogram acquisition simultaneous with left atrial pressure measurement during fast intravascular fluid bolus administration. We showed that patients undergoing “heat acclimatization combined with exercise training” were less susceptible to ischemic injury, therefore expressing less diastolic dysfunction after cardiopulmonary bypass compared to non-acclimatized patients. This was the first clinical translational study on cardiac patients, while exploiting environmental harsh conditions for human benefits. The original experimental data are described and discussed in view of the past as well as the present knowledge of the protective mechanisms induced by Heat Acclimation Mediated Cross-tolerance.

Background Congestive heart failure (CHF) is a significant health care burden in developed countries. However, the molecular events leading from cardiac hypertrophy to CHF are unclear and preventive therapeutic approaches are limited. We have previously described that microphthalmia-associated transcription factor (MITF) is a key regulator of cardiac hypertrophy, but its cardiac targets are still uncharacterized. Methods and results Gene array analysis of hearts from MITF-mutated mice indicated that ErbB2 interacting protein (Erbin) is a candidate target gene for MITF. We have recently demonstrated that Erbin is decreased in human heart failure and plays a role as a negative modulator of pathological cardiac hypertrophy. Here we show that Erbin expression is regulated by MITF. Under basal conditions MITF activates Erbin expression by direct binding to its promoter. However, under β-adrenergic stimulation Erbin expression is decreased only in wild type mice, but not in MITF-mutated mice. Yeast two-hybrid screening, using MITF as bait, identified an interaction with the cardiac-predominant four-and-a-half LIM domain protein 2 (FHL2), which was confirmed by co-immunoprecipitation in both mouse and human hearts. Upon β-adrenergic stimulation, FHL2 and MITF bind Erbin promoter as a complex and repress MITF-directed Erbin expression. Overexpression of FHL2 alone had no effect on Erbin expression, but in the presence of MITF, Erbin expression was decreased. FHL2–MITF association was also increased in biopsies of heart failure patients. Conclusion MITF unexpectedly regulates both the activation and the repression of Erbin expression. This ligand mediated fine tuning of its gene expression could be an important mechanism in the process of cardiac hypertrophy and heart failure.

The management of acute Stanford Type A intramural hematoma (IMH) of the aorta remains controversial. Most surgeons advocate emergency surgery in a manner similar to frank acute Type A dissection. Others recommend a conservative approach to this distinct clinicopathological entity. We describe a case of acute aortic pathology initially diagnosed as Type A IMH with organ malperfusion, subsequently identified as acute Type B pathology with retrograde and antegrade extension. An endovascular approach was successfully used to exclude the site of origin.

Background Presenting systolic blood pressure (SBP) is a powerful predictor of mortality in many cardiovascular settings, including acute coronary syndromes, cardiogenic shock, and acute heart failure. Objectives This study evaluated the association of presenting SBP with in-hospital outcomes, specifically all-cause mortality, in acute aortic dissection (AAD). Methods The study included 6,238 consecutive patients (4,167 with type A and 2,071 with type B AAD) enrolled in the International Registry of Acute Aortic Dissection. Patients were stratified in 4 groups according to presenting SBP: SBP >150, SBP 101 to 150, SBP 81 to 100, or SBP ≤80 mm Hg. Results The relationship between presenting SBP and in-hospital mortality displayed a J-curve association, with significantly higher mortality rates in patients with very high SBP (26.3% for SBP >180 mm Hg in type A AAD, 13.3% for SBP >200 mm Hg in type B AAD; p = 0.005 and p = 0.018, respectively) as well as in those with SBP ≤100 mm Hg (29.9% in type A, 22.4% in type B; p = 0.033 and p = 0.015, respectively). This relationship was mainly from increased rates of in-hospital complications (acute renal failure, coma, and mesenteric ischemia/infarction in patients with SBP >150 mm Hg; stroke, coma, cardiac tamponade, myocardial ischemia/infarction, and acute renal failure in patients with SBP ≤80 mm Hg). Notably, presenting SBP ≤80 mm Hg was independently associated with in-hospital mortality in both type A (p = 0.001) and type B AAD (p = 0.003). Conclusions Presenting SBP showed a clear J-curve relationship with in-hospital mortality in patients with AAD. Although this association was related to increased rates of comorbid conditions at the edges of the curve, SBP ≤80 mm Hg was an independent correlate of in-hospital mortality.

BACKGROUND: Previous studies demonstrated that left atrium (LA) size is associated with mortality in an elderly population. It remains unclear whether indices of LA function including reservoir, conduit, or booster elements of LA function provide incremental prognostic information. HYPOTHESIS: Echocardiographic measures of the various parameters of LA function would predict 5‐year mortality in a community‐dwelling population of 85 to 86 year olds independently of LA volume. METHODS: Subjects ages 85 to 86 years old underwent home echocardiography. LA volumes were assessed by the biplane Simpson's method from apical views using measurements of phasic volumes and functions of the LA, including LA expansion index. LA passive and active emptying fractions were assessed. Survival status at 5‐year follow‐up was assessed. RESULTS: Two hundred eighty‐two subjects were included, of whom 87 (31%) had died at follow‐up. Survival of the subjects in the lowest quartile of the LA expansion index as well as LA active filling index was significantly lower. When measurements of LA volume index were added to the model, the relationship between survival and indices of LA function remained significant. CONCLUSIONS: This study demonstrated that elderly subjects aged 85 to 86 years with significantly impaired LA function had increased 5‐year mortality independently of indices of LA volume.

ErbB2 interacting protein (Erbin) is a widely expressed protein and participates in inhibition of several intracellular signaling pathways. Its mRNA has been found to be present in relatively high levels in the heart. However, its physiological role in the heart has not been explored. In the present work, we elucidated the role of Erbin in cardiac hypertrophy. Cardiac hypertrophy was induced in mice either by isoproterenol administration or by aortic constriction. The level of Erbin was significantly decreased in both models. Erbin(-/-) mice rapidly develop decompensated cardiac hypertrophy, and following severe pressure overload all Erbin(-/-) mice died from heart failure. Down-regulation of Erbin expression was also observed in biopsies derived from human failing hearts. It is known that Erbin inhibits Ras-mediated activation of the extracellular signal-regulated kinase (ERK) by binding to Soc-2 suppressor of clear homolog (Shoc2). Our data clearly show that ERK phosphorylation is enhanced in the heart tissues of Erbin(-/-) mice. Furthermore, we clearly demonstrate here that Erbin associates with Shoc2 in both whole hearts and in cardiomyocytes, and that in the absence of Erbin, Raf is phosphorylated and binds Shoc2, resulting in ERK phosphorylation. In conclusion, Erbin is an inhibitor of pathological cardiac hypertrophy, and this inhibition is mediated, at least in part, by modulating ERK signaling.

A new murmur of aortic insufficiency is a classic physical examination sign of acute aortic dissection (AAD); we sought to further describe AAD patients presenting with aortic insufficiency murmur without a prior history of aortic valve disease or repair. Patients enrolled from January 1996- June

Objective: Bicuspid aortic valve (BAV) is the most common congenital heart malformation (>1%). Patients with BAV are at risk to develop complications, some are life threatening. Previous studies ha...