Carolyn M. Larsen

The prognostic significance of tricuspid valve regurgitation in pulmonary arterial hypertension

Tricuspid valve regurgitation (TR) is a frequent finding in patients with pulmonary arterial hypertension (PAH). However, its prognostic significance and relation to PAH, while suspected, are poorly understood. We assessed 727 consecutive patients with newly diagnosed PAH who underwent transthoracic echocardiographic evaluation of tricuspid valve function.

Effect of Body Mass Index on Exercise Capacity in Patients With Hypertrophic Cardiomyopathy

The objective of this study was to evaluate the relation between body mass index (BMI), exercise capacity, and symptoms in patients with hypertrophic cardiomyopathy (HC) and to utilize results of cardiopulmonary exercise tests (CPX) and transthoracic echocardiograms to understand the mechanism(s) of reduced exercise capacity across body mass index groups. Over a 6-year period, 510 consecutive patients with HC seen at a tertiary referral center underwent (CPX) and a transthoracic echocardiogram. Increasing BMI was associated with decreased exercise capacity as assessed by peak VO2 (ml/kg/min). However, the prevalence of cardiac impairment did not vary by BMI group. In conclusion, these findings suggest that in some patients with hypertrophic cardiomyopathy, cardiac impairment is not the primary cause of exercise limitation and weight loss may result in improved exercise capacity.

Incremental value of 3D over 2D echocardiography in a patient with multiple ICD leads in the right ventricle

A 65-year-old male with dyspnoea and oedema from severe tricuspid regurgitation was referred for tricuspid valve (TV) surgery. He had undergone placement of a dual-chamber implantable cardioverter defibrillator (ICD) 15 years prior for dilated cardiomyopathy that was upgraded to a biventricular system with placement of a new right ventricular lead 3 years ago. Intraoperative 2D …

Comparison of Valsalva Maneuver, Amyl Nitrite, and Exercise Echocardiography to Demonstrate Latent Left Ventricular Outflow Obstruction in Hypertrophic Cardiomyopathy

Guidelines recommend exercise stress echocardiogram (ESE) for patients with hypertrophic cardiomyopathy (HC) if a 50 mm Hg gradient is not present at rest or provoked with Valsalva or amyl nitrite, to direct medical and surgical management. However, no study has directly compared all 3 methods. We sought to evaluate efficacy and degree of provocation of left ventricular outflow gradients by ESE, and compare with Valsalva and amyl nitrite. In patients with HC between 2002 and 2015, resting echocardiograms and ESEs within 1 year were retrospectively reviewed. Gradients elicited by each provocation method were compared. Rest and ESE were available in 97 patients (mean age 54 ± 18 years, 57% male); 78 underwent Valsalva maneuver and 41 amyl nitrite provocation. Median gradients (interquartile range) were 10 mm Hg (7,19) at rest, 16 mm Hg (9,34) with Valsalva, 23 mm Hg (13,49) with amyl nitrite, and 26 mm Hg (13,58) with ESE. ESE and amyl nitrite were able to provoke obstruction (≥30 mm Hg) and severe obstruction (≥50 mm Hg) more frequently than Valsalva. In patients with resting gradient <30 mm Hg (n = 83), provocation maneuvers demonstrated dynamic obstruction in 51%; in those with Valsalva gradient <30 mm Hg (n = 57), ESE or amyl nitrite provoked a gradient in 44%; and in those with amyl nitrite gradient <30 mm Hg (n = 20), ESE provoked a gradient in 29%. No demographic or baseline echocardiographic parameter predicted provocable obstruction. In conclusion, ESE is clinically useful; however, different provocation maneuvers may be effective in different patients with HC, and all maneuvers may be required to provoke dynamic obstruction in symptomatic patients.

Cardiovascular effects of the addition of nilotinib to standard therapy for acute myeloid leukemia

Nilotinib is a second-generation tyrosine kinase inhibitor (TKI), which inhibits the activity of KIT, BCR-ABL, PDGF-A, PDGF-B and FLT-3 [1]. KIT is involved in regulating proliferation and apoptosis in leukemic cells [2,3]. In acute myeloid leukemia (AML), c-kit expression is associated with shorter progression-free and overall survival [4]. The addition of nilotinib to standard induction therapy for AML is being studied in the DATA trial (phase-II study of combination daunorubicin, cytArabine and nilotinib [TAsigna] in patients newly diagnosed with AML and KIT overexpression) (NCT01806571). Standard induction therapy for AML includes an anthracycline backbone with a known cardiac toxicity risk [5]. Left ventricular dysfunction has also been reported with nilotinib, but not as frequently as arterial vascular occlusive events and QTc prolongation [6,7]. Intriguingly, in vitro testing has demonstrated that nilotinib decreases human cardiomyocyte viability and increases cardiomyocyte superoxide generation and caspase activation [8]. Thus, the combination of an anthracycline and nilotinib may result in increased adverse cardiac events but this has not been extensively studied [9]. We retrospectively reviewed cardiovascular outcomes in AML patients treated with standard induction therapy (an anthracycline plus cytarabine [7þ 3]) in comparison to KIT positive AML patients, defined by CD117 positivity on flow cytometry, treated with 7þ 3 plus nilotinib in the context of the DATA trial. Our objective was to determine whether the combination of nilotinib and 7þ 3 increased the risk of adverse cardiovascular events when compared to 7þ 3 alone. Institutional review board approval for this study was obtained. One hundred consecutive patients treated for newly diagnosed AML at Mayo Clinic in Rochester, MN from 1 June 2010 to 31 October 2014 were identified from the institutional leukemia database and retrospective chart review performed to assess cardiovascular outcomes. Included patients had previously consented to the use of their medical records for clinical research. The primary endpoint was congestive heart failure (CHF) defined by the modified Framingham criteria [10]. Secondary endpoints included cancer therapeutics-related cardiac dysfunction (CTRCD) defined as a >10% decrease in left ventricular ejection fraction (LVEF) to an LVEF of <53% per consensus recommendation, arrhythmias, defined as a new rhythm abnormality other than sinus bradycardia or tachycardia resulting in a change to therapy or transfer to a higher level of care, acute coronary syndromes diagnosed by a cardiologist, and deep vein thrombosis (DVT), pulmonary emboli (PE), acute arterial occlusive events and stroke diagnosed by the treating clinician [11]. The doxorubicin isotoxic dose was calculated according to Children’s Oncology Group recommendations as follows: 1 (cumulative doxorubicin dose mg/m)þ 1 (cumulative daunorubicin dose mg/m)þ 5 (cumulative idarubicin dose mg/m)þ 4 (cumulative mitoxantrone dose mg/m) [12]. Thirteen patients (13%) diagnosed with AML who received nilotinib plus 7þ 3 as subjects in the DATA trial and 87 patients (87%) who received standard therapy with 7þ 3 were identified. Nilotinib was dosed at 300mg by mouth twice daily on days 4–14 per 14-day cycle. After completion of consolidation therapy, nilotinib was continued at a dose of 300mg twice daily for up to 2 years. None of the patients had a prior exposure to nilotinib (or any other TKI). The median duration of exposure to nilotinib was 83 days (interquartile range [IQR] 18–234 days). The anthracycline in the regimen was idarubicin for 80% of patients and daunorubicin for 20%. After initial treatment, 20% of patients had exposure to mitoxantrone as a component of subsequent salvage regimens. Six percent of patients had prior exposure to doxorubicin for the treatment of breast cancer (n1⁄4 4) or non-Hodgkin lymphoma (n1⁄4 2) (Table 1). The median current therapy doxorubicin isotoxic and the cumulative doxorubicin isotoxic dose did not differ significantly between groups (Table 1). While there were no significant differences in baseline cardiovascular risk factors, the overall trends may suggest

Pivotal Role of Intraoperative Transesophageal Echocardiography for Detecting Iatrogenic Aortic Regurgitation due to Cardiac Catheterization

https://e-kcj.org A 67-year-old man with a history of fatigue and dyspnea on exertion was diagnosed with atrial fibrillation and severe mitral regurgitation. Preoperative transthoracic echocardiography (TTE) showed a normal aortic valve without aortic regurgitation (Figure 1 and Supplementary Video 1) and bileaflet mitral valve prolapse with severe mitral regurgitation. As part of the preoperative evaluation, cardiac catheterization was performed, which showed normal coronary arteries. The patient was referred for mitral valve repair.

Thrombocytopenia independently predicts death in idiopathic PAH

Background: Pulmonary arterial hypertension (PAH) is a progressive vascular disorder with a high mortality. Clinical experience and small case series suggest thrombocytopenia may be frequent in this population and associated with a poor prognosis. We sought to estimate the prevalence of thrombocytopenia in patients with PAH and characterize its association with disease characteristics and patient outcome. Methods: Single center cohort study of 714 incident adult patients with Group 1 PH who were evaluated for baseline platelet count at the time of diagnosis. Pts were stratified into three groups: normal platelet count (>150 × 109/L), Grade 1 thrombocytopenia (75–149 × 109/L) and Grade 2–4 thrombocytopenia (<75 × 109/L). Results: The median platelet count was 209 × 109/L (IQR 163, 264). There were 572 (80%) pts without thrombocytopenia, 107 (15%) with Grade 1 and 35 (5%) with Grade 2–4 thrombocytopenia. The median pt age was 55 years (IQR 44–65) with no difference between platelet groups (p = 0.85). Men were more likely to have thrombocytopenia (62, 34%) than women (80, 15%, p < 0.0001). Thrombocytopenia was frequent with portopulmonary PAH (84%) as opposed to idiopathic PAH (iPAH; 14%) or connective tissue disease associated PAH (12%). Platelet counts were not associated with functional class symptoms, the degree of right ventricular enlargement or dysfunction or tricuspid regurgitation by echocardiography. Invasive hemodynamics of right atrial pressure, mean pulmonary artery pressure and pulmonary vascular resistance were also similar between platelet groups. Thrombocytopenia was associated with higher mortality in iPAH patients (age‐ and sex‐adjusted 5 year mortality [HR 1.95 (1.20, 3.08) p = 0.008] but not in other etiology groups. In a multivariate model of iPAH patients (adjusted for age, sex, DLCO, PVR, creatinine and 6MW distance) thrombocytopenia was most predictive of 5‐year mortality [HR 1.68 (1.32, 2.12), p < 0.0001]. Conclusion: Thrombocytopenia in the context of iPAH portends a poor prognosis and is a simple independent factor to consider in judging severity of disease.

LONG-TERM ANTICOAGULATION MANAGEMENT AFTER RIGHT ATRIAL THROMBUS ASSOCIATED WITH ASD CLOSURE

Right atrial (RA) thrombi are a rare complication after surgical atrial septal defect (ASD) closure. A 24 year old woman presented for recommendations regarding anticoagulation management in the setting of a desire for future pregnancy. She underwent surgical closure of a secundum ASD with a bovine

34-Year-Old Woman With Abdominal Pain and Blood-Streaked Diarrhea

A 34-year-old woman presented to the emergency department for evaluation of a 12-hour history of sudden severe epigastric pain and bilateral leg weakness during exercise associated with nausea and vomiting. She experienced 2 episodes of diarrhea; 1 of which was blood streaked. The patient reported not eating or drinking much that day. She described a few previous less severe episodes of abdominal pain and diarrhea since childhood associated with certain foods. She denied fever or chills but reported a 5-lb intentional weight loss during the past month. She denied changes in her appetite, myalgia, arthralgia, or vision changes. She had no recent travel, sick contacts, or antibiotic drug use. She denied current pregnancy.