Ryan J. Koene

Shared Risk Factors in Cardiovascular Disease and Cancer

Cardiovascular disease (CVD) and cancer are the 2 leading causes of death worldwide. Although commonly thought of as 2 separate disease entities, CVD and cancer possess various similarities and possible interactions, including a number of similar risk factors (eg, obesity, diabetes mellitus), suggesting a shared biology for which there is emerging evidence. Although chronic inflammation is an indispensable feature of the pathogenesis and progression of both CVD and cancer, additional mechanisms can be found at their intersection. Therapeutic advances, despite improving longevity, have increased the overlap between these diseases, with millions of cancer survivors now at risk of developing CVD. Cardiac risk factors have a major impact on subsequent treatment-related cardiotoxicity. In this review, we explore the risk factors common to both CVD and cancer, highlighting the major epidemiological studies and potential biological mechanisms that account for them.

Assessment of the Myogenic Stem Cell Compartment Following Transplantation of Pax3/Pax7-Induced Embryonic Stem Cell-Derived Progenitors

An effective long‐term cell therapy for skeletal muscle regeneration requires donor contribution to both muscle fibers and the muscle stem cell pool. Although satellite cells have these abilities, their therapeutic potential so far has been limited due to their scarcity in adult muscle. Myogenic progenitors obtained from Pax3‐engineered mouse embryonic stem (ES) cells have the ability to generate myofibers and to improve the contractility of transplanted muscles in vivo, however, whether these cells contribute to the muscle stem cell pool and are able to self‐renew in vivo are still unknown. Here, we addressed this question by investigating the ability of Pax3, which plays a critical role in embryonic muscle formation, and Pax7, which is important for maintenance of the muscle satellite cell pool, to promote the derivation of self‐renewing functional myogenic progenitors from ES cells. We show that Pax7, like Pax3, can drive the expansion of an ES‐derived myogenic progenitor with significant muscle regenerative potential. We further demonstrate that a fraction of transplanted cells remains mononuclear, and displays key features of skeletal muscle stem cells, including satellite cell localization, response to reinjury, and contribution to muscle regeneration in secondary transplantation assays. The ability to engraft, self‐renew, and respond to injury provide foundation for the future therapeutic application of ES‐derived myogenic progenitors in muscle disorders. STEM CELLS 2011;29:777–790

Adrenal hypofunction from histoplasmosis: a literature review from 1971 to 2012

PurposeWhile histoplasmosis has been reported from most continents, the disease is most often recognized in the midwestern United States. The recent diagnosis of adrenal hypofunction in two patients with progressive disseminated histoplasmosis (PDH) in our hospital led us to review the literature.MethodsWe reviewed PubMed using the search term “adrenal histoplasmosis” for the years 1971 to 2012.ResultsThe results included 242 patients with adrenal histoplasmosis from either case reports or case series. Most of the reported patients were from countries not previously considered to be heavily endemic for histoplasmosis. In addition, 41.3 % of patients with adrenal involvement developed adrenal hypofunction.ConclusionAs modern technology elucidates more cases of adrenal histoplasmosis, the global boundaries of endemicity are being redefined.

Effect of coronary artery bypass grafting on left ventricular ejection fraction in men eligible for implantable cardioverter-defibrillator

Implantable cardioverter-defibrillator (ICD) therapy for primary prevention of sudden cardiac death is not routinely recommended within 90 days of coronary artery bypass grafting (CABG) because of the possibility of an improvement in left ventricular ejection fraction (EF) to>35% after revascularization. We sought to determine the incidence and predictors of EF improvement to >35% after isolated CABG in patients who had a preoperative EF ≤35%. We studied 375 patients who underwent CABG at a tertiary institution and had an echocardiogram preoperatively and postoperatively. Of these, 74 patients (20%) with a preoperative EF ≤35% were included in this analysis. Improvement in EF was defined as postoperative EF >35%. In the overall study population (n = 74), mean EF improved from 28 ± 6% preoperatively to 36 ± 12% postoperatively (p <0.0001). A total of 38 patients (51%) had postoperative improvement in EF to >35% (mean EF in these patients increased from 30 ± 5% to 46 ± 8%; p <0.0001). Patients with EF improvement had a higher preoperative EF than those with no improvement (30 ± 5% vs 26 ± 7%, p <0.005). Improvement in EF was 5 times more likely in patients with preoperative EF 26% to 35% (odds ratio 4.95, 95% CI 1.73 to 14.1; p = 0.003) than those with preoperative EF ≤25%. Other clinical characteristics were not significantly different between patients with versus without EF improvement. In conclusion, more than half of the ICD-eligible patients who underwent CABG improved their EF to >35% after surgery and became ineligible for a primary prevention ICD. EF improvement was unlikely in patients with preoperative EF <25%.

HAS-BLED and CHA2DS2-VASc Scores as Predictors of Bleeding and Thrombotic Risk After Continuous-Flow Ventricular Assist Device Implantation

BACKGROUND HAS-BLED and CHA₂DS₂-VASc scores predict bleeding in patients on anticoagulation and thromboembolic (TE) risk in patients with atrial fibrillation, respectively. We hypothesized that these scores would be predictive of bleeding and TE complications following continuous-flow ventricular assist device (CF-VAD) implantation. METHODS AND RESULTS Baseline HAS-BLED and CHA2DS2-VASc scores were retrospectively determined for 173 consecutive patients who underwent HeartMate II CF-VAD implantation at a single center from 2005 to 2011. Forty-three patients had bleeding (24.9%) and 22 had TE (12.7%) events over a 290 patient-year follow-up period. The mean ± SD HAS-BLED scores were 2.7 ± 1.0 and 1.9 ± 1.1 (P < .0001) in patients with and without bleeding, respectively. The CHA₂DS₂-VASc scores were 3.6 ± 1.4 and 2.9 ± 1.5 (P = .03) in patients with and without TE events, respectively. A HAS-BLED score of ≥ 3 was associated with a significantly higher risk of bleeding events compared with a score of <3 (42% vs 15%, respectively; hazard ratio [HR] 3.40, 95% confidence interval [CI] 1.82-6.32; P < .001). A CHA₂DS₂-VASc score of ≥ 3 was associated with a higher risk of TE events compared with a score of <3 (18% vs 4%, respectively; HR 4.02, 95% CI 1.19-13.6; P = .025). CONCLUSIONS Baseline HAS-BLED and CHA₂DS₂-VASc scores of ≥ 3 conferred significantly higher risks of bleeding and TE, respectively, following HeartMate II implantation.

Acute Heart Failure From Lyme Carditis

Carditis can complicate Lyme disease in an estimated <5% of cases, but cardiogenic shock is rare. We report a case of severe biventricular heart failure as a manifestation of a Jarisch-Herxheimer reaction in a patient with early Lyme disease following treatment with ceftriaxone. ### Case Report A 47-year-old woman presented with subacute fever, erythema migrans-like rash, shortness of breath, and spells of dizziness that had progressed to “blackouts.” At admission, complete atrioventricular (AV) block was present (Figure 1A), and ceftriaxone 1g was given initially for suspected Lyme disease. Within 6 hours of antimicrobial treatment, she developed polymorphic ventricular tachycardia (Figure 1B). She was resuscitated with intravenous magnesium, a 150 mg bolus of amiodarone, and defibrillation. Once stabilized, echocardiography revealed severe biventricular heart failure with left ventricular ejection fraction (LVEF) of 10%. Inotrope support was initiated. On hospital day 2, coronary angiography demonstrated patent epicardial coronary arteries, and endomyocardial biopsy revealed diffuse lymphocytic myocarditis (Figure 2). On day 3, methylprednisolone 1000 mg was administered daily for 3 days, followed by a 12-day taper of oral …

Effect of sleep-disordered breathing on appropriate implantable cardioverter-defibrillator therapy in patients with heart failure: A systematic review and meta-analysis

Background— Patients with heart failure and reduced ejection fraction are at increased risk of malignant ventricular arrhythmias. Implantable cardioverter-defibrillator (ICD) is recommended to prevent sudden cardiac death in some of these patients. Sleep-disordered breathing (SDB) is highly prevalent in this population and may impact arrhythmogenicity. We performed a systematic review and meta-analysis of prospective studies that assessed the impact of SDB on ICD therapy. Methods and Results— Relevant prospective studies were identified in the Ovid MEDLINE, EMBASE, and Google Scholar databases. Weighted risk ratios of the association between SDB and appropriate ICD therapies were estimated using random effects meta-analysis. Nine prospective cohort studies (n=1274) were included in this analysis. SDB was present in 52% of the participants. SDB was associated with a 55% higher risk of appropriate ICD therapies (45% versus 28%; risk ratio, 1.55; 95% confidence interval, 1.32–1.83). In a subgroup analysis based on the subtypes of SDB, the risk was higher in both central (risk ratio, 1.50; 95% confidence interval, 1.11–2.02) and obstructive (risk ratio, 1.43; 95% confidence interval, 1.01–2.03) sleep apnea. Conclusions— SDB is associated with an increased risk of appropriate ICD therapy in patients with heart failure and reduced ejection fraction.

Safety and Outcomes of Capsule Endoscopy in Patients with Left Ventricular Assist Device: a Single-Center Retrospective Case Series.

Obscure gastrointestinal bleeding (GIB) in patients with continuous-flow left ventricular assist devices (CF-LVAD) is common. Capsule endoscopy (CE) can be used in the diagnosis of obscure GIB. Safety and outcomes of CE in patients with CF-LVAD are unknown. The aim is to define the safety and outcomes of CE in this population. Paitents with CF-LVAD undergoing CE at a single center between 2007 and 2014 were retrospectively reviewed. Thirty-four CE studies were performed. Positive CE occurred in 19 studies. No clinically significant cardiac events occurred. Medical intervention was the most common management strategy. Rebleeding after CE occurred in 10 patients. Patients with active bleeding or lesions such as arteriovenous malformations (AVM) incurred a higher risk of rebleeding, transfusion, and repeated endoscopy. CE is safe in patients with CF-LVAD. The risk of rebleeding was more common in patients with active bleeding or AVM lesions although this result did not reach statistical significance.

A case of cerebral venous sinus thrombosis associated with Crohn’s disease: dilemma in management

Inflammatory bowel disease (IBD) is known to increase the risk of venous thromboembolism. Cerebral venous sinus thrombosis (CVST) is a rare but important complication of IBD. Timely diagnosis, particularly in younger patients, requires a high level of suspicion in order to prevent potentially devastating complications such as hemorrhage or venous infarction. The paper presents a 44-year-old Caucasian woman with a previous history of Crohn’s disease and deep venous thrombosis. Magnetic resonance imaging confirmed the diagnosis of CVST. Achieving therapeutic anticoagulation with warfarin was difficult, due to presumed pharmacological interaction between warfarin and 6-mercaptopurine. Clinicians should have a high index of suspicion for CVST when a patient with Crohn’s disease presents with acute headache, and be aware of challenges related to medical management.

Echocardiographic Predictors of Sudden Cardiac Death The Atherosclerosis Risk in Communities Study and Cardiovascular Health Study

Background— This study assessed the echocardiographic predictors of sudden cardiac death (SCD) within 2 population-based cohorts. Methods and Results— Echocardiograms were obtained on 2383 participants (1993–1995) from the ARIC study (Atherosclerosis Risk in Communities; 100% black) and 5366 participants (1987–1989 and 1994–1995) from the CHS (Cardiovascular Health Study). The main outcome was physician-adjudicated SCD. We used Cox proportional-hazards models with incident coronary heart disease and heart failure as time-dependent covariates to assess the association between echocardiographic variables and SCD, adjusting for Framingham risk score variables, coronary heart disease, and renal function. Cohort-specific results were meta-analyzed. During a median follow-up of 7.3 and 13.1 years, 44 ARIC study participants and 275 CHS participants had SCD, respectively. In the meta-analyzed results, the adjusted hazard ratios (95% confidence intervals) for predictors of SCD were 3.07 (2.29–4.11) for reduced left ventricular ejection fraction; 1.85 (1.36–2.52) for mitral annular calcification; 1.64 (1.07–2.51) for mitral E/A >1.5, and 1.52 (1.14–2.02) for mitral E/A <0.7 (versus mitral E/A 0.7–1.5); 1.30 (1.15–1.48) per 1 SD increase in left ventricular mass; and 1.15 (1.02–1.30) per 1 SD increase in left atrial diameter. A receiver-operating characteristic model for prediction of SCD using Framingham risk score variables had a C statistic of 0.61 for ARIC study and 0.67 for CHS; the full multivariable model including all echocardiographic variables had a C statistic of 0.76 for ARIC study and 0.74 for CHS. Conclusions— In addition to reduced left ventricular ejection fraction, we identified other echocardiographic-derived variables predictive for SCD that provided incremental value compared with clinical risk factors.Background—This study assessed the echocardiographic predictors of sudden cardiac death (SCD) within 2 population-based cohorts. Methods and Results—Echocardiograms were obtained on 2383 participants (1993–1995) from the ARIC study (Atherosclerosis Risk in Communities; 100% black) and 5366 participants (1987–1989 and 1994–1995) from the CHS (Cardiovascular Health Study). The main outcome was physician-adjudicated SCD. We used Cox proportional-hazards models with incident coronary heart disease and heart failure as time-dependent covariates to assess the association between echocardiographic variables and SCD, adjusting for Framingham risk score variables, coronary heart disease, and renal function. Cohort-specific results were meta-analyzed. During a median follow-up of 7.3 and 13.1 years, 44 ARIC study participants and 275 CHS participants had SCD, respectively. In the meta-analyzed results, the adjusted hazard ratios (95% confidence intervals) for predictors of SCD were 3.07 (2.29–4.11) for reduced left ventricular ejection fraction; 1.85 (1.36–2.52) for mitral annular calcification; 1.64 (1.07–2.51) for mitral E/A >1.5, and 1.52 (1.14–2.02) for mitral E/A <0.7 (versus mitral E/A 0.7–1.5); 1.30 (1.15–1.48) per 1 SD increase in left ventricular mass; and 1.15 (1.02–1.30) per 1 SD increase in left atrial diameter. A receiver-operating characteristic model for prediction of SCD using Framingham risk score variables had a C statistic of 0.61 for ARIC study and 0.67 for CHS; the full multivariable model including all echocardiographic variables had a C statistic of 0.76 for ARIC study and 0.74 for CHS. Conclusions—In addition to reduced left ventricular ejection fraction, we identified other echocardiographic-derived variables predictive for SCD that provided incremental value compared with clinical risk factors.