Incorporating a Genetic Risk Score Into Coronary Heart Disease Risk Estimates: Effect on Low-Density Lipoprotein Cholesterol Levels (the MI-GENES Clinical Trial).

BACKGROUND: Whether knowledge of genetic risk for coronary heart disease (CHD) affects health-related outcomes is unknown. We investigated whether incorporating a genetic risk score (GRS) in CHD risk estimates lowers low-density lipoprotein cholesterol (LDL-C) levels. METHODS AND RESULTS: Participants (n=203, 45-65 years of age, at intermediate risk for CHD, and not on statins) were randomly assigned to receive their 10-year probability of CHD based either on a conventional risk score (CRS) or CRS + GRS ((+)GRS). Participants in the (+)GRS group were stratified as having high or average/low GRS. Risk was disclosed by a genetic counselor followed by shared decision making regarding statin therapy with a physician. We compared the primary end point of LDL-C levels at 6 months and assessed whether any differences were attributable to changes in dietary fat intake, physical activity levels, or statin use. Participants (mean age, 59.4±5 years; 48% men; mean 10-year CHD risk, 8.5±4.1%) were allocated to receive either CRS (n=100) or (+)GRS (n=103). At the end of the study period, the (+)GRS group had a lower LDL-C than the CRS group (96.5±32.7 versus 105.9±33.3 mg/dL; P=0.04). Participants with high GRS had lower LDL-C levels (92.3±32.9 mg/dL) than CRS participants (P=0.02) but not participants with low GRS (100.9±32.2 mg/dL; P=0.18). Statins were initiated more often in the (+)GRS group than in the CRS group (39% versus 22%, P<0.01). No significant differences in dietary fat intake and physical activity levels were noted. CONCLUSIONS: Disclosure of CHD risk estimates that incorporated genetic risk information led to lower LDL-C levels than disclosure of CHD risk based on conventional risk factors alone. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01936675.

Differences in Baseline Characteristics and Outcomes in Young Caucasians and African Americans with Acute Myocardial Infarction.

BACKGROUND: The incidence of acute myocardial infarction (AMI) in young patients is increasing. While race-related differences in clinical characteristics and outcomes for older AMI patients have been well-studied, such differences in young patients are unknown. METHODS: We performed a retrospective review of charts of Caucasian and African American (AA) patients <50 years of age, presenting with AMI between 2010 and 2017 in an urban, community hospital in Detroit, Michigan. RESULTS: A total of 271 patients were identified with 156 being AAs (57.5%). Mean age was 43 years which was similar in both groups. AAs with AMI were 2.2 times more likely to be women and to have a history of diabetes and 1.2 times more likely to have BMI >30 kg/m2. History of coronary artery disease (1.8-fold) and hypertension (1.5-fold) were also more common in AAs. Overall presenting features were similar, other than that AAs presented more often with non-ST-elevation MI and tended to present less often with cardiac arrest. No differences were observed in the angiographic findings or in-hospital outcomes in the two groups, with the exception of lower need of mechanical support in AAs. CONCLUSIONS: In conclusion, our data provide important, not previously described information on race-related differences in history, presentation, clinical and angiographic features and outcomes in AAs compared with Caucasians younger than 50 with AMI. These findings may have implications for tailoring specific preventive strategies to decrease the incidence of AMI and its associated adverse events in both racial groups.

A case report of eustachian valve endocarditis due to Salmonella typhimurium in an AIDS patient.

INTRODUCTION: The eustachian valve is a normal remnant of the right valve of the sinus venosus, which directs blood in the embryo life from the inferior vena cava into the left atrium through the foramen ovale. CASE REPORT: We report a case of eustachian valve endocarditis (EVE) secondary to Salmonella typhimurium in a patient with acquired immunodeficiency syndrome (AIDS). The patient also had concomitant Pneumocystis pneumonia. DISCUSSION: Salmonella bacteremia is one of the AIDS-defining illnesses, and many patients will have recurrent episodes. Salmonella endocarditis on the other hand is rare, but when present, it has a significant morbidity and mortality. EVE rarely requires surgical intervention, and the appropriate antibiotics are the treatment of choice. CONCLUSIONS: We recommend clinicians to consider obtaining an echocardiography in AIDS patients with Salmonella bacteremia to search for possible endocarditis, as it does change the treatment plan.

Gemella endocarditis: A case report and a review of the literature.

Infective endocarditis (IE) remains a prevalent disease with a high rate of morbidity and mortality. Recent changes have been noted in the profile of causative microorganisms. In this report, we describe a case of Gemella-related endocarditis and review the related literature. Our patient was an 81-year-old man who presented with dyspnea and fatigue. His initial examination revealed a new systolic murmur. Echocardiogram revealed moderate mitral regurgitation with 1-cm mass on the anterior mitral leaflet, and blood cultures grew Gemella haemolysans. Penicillin and gentamicin were initiated, and workup for possible source was positive for a colonic polyp with high-grade dysplasia. The patient subsequently developed cardiogenic shock and severe pulmonary edema. Comfort care measures were initiated, and he passed away thereafter. We reviewed PubMed for cases of Gemella-related endocarditis. We found 65 documented cases and added our patient's case to the analysis. Seventy-two percent of the cases occurred in men. The mean age was 51 years and 42% of the patients were older than 60 years. Fever was the most common presenting symptom and most of the cases presented subacutely. The mitral valve was the most affected site and 50% of the patients required surgical intervention. G. morbillorum was the most common subtype and a total of four cases were found to be associated with colorectal neoplasm. As a conclusion, Gemella species rarely cause IE. The absence of a clear source of bacteremia warrants further evaluation for a gastrointestinal source. The infection can be destructive and must be promptly treated to avoid complications.

Endocarditis due to Neisseria elongata: A case report and review of the literature.

INTRODUCTION: Neisseria elongata, which is part of the normal oropharyngeal bacterial flora, can be an aggressive organism causing serious infections including infective endocarditis. N. elongata infective endocarditis is rare and no current guidelines exist to direct antibiotic selection and/or duration of treatment. CASE REPORT: We report a case of infective endocarditis due to N. elongata and a review of the literature. Our patient is a healthy young woman, who was found to have an aortic root abscess with valve perforation requiring valve replacement. DISCUSSION: N. elongata infective endocarditis typically affects the left cardiac chambers and is associated with high risk of embolization. A transesophageal echocardiogram should be performed as part of the initial workup to assess the extent of infection, as a high percentage of patients develop perivalvular abscess formation and/or valve perforation. Most patients require prolonged antibiotic therapy and early surgical intervention. CONCLUSIONS: This case demonstrates the potential severity of N. elongata endocarditis. Further studies are needed to establish management guidance.

Coronary Artery Embolism: Two Case Reports and a Review of the Literature.

Coronary embolism (CE) is an uncommon and unique cause of acute myocardial infarction. In this report, we review 216 cases of CE including 2 new cases from our institution. The mean patient age was 52.5 years and 62% of the patients were males. Chest pain was the most common presenting symptom followed by dyspnea, and the most commonly affected vessel was the left anterior descending artery. Leading etiologies of the embolus were atrial fibrillation, septic emboli, and iatrogenic causes. Treatment approaches varied with thrombus aspiration being used in 30% of cases. In-hospital mortality rate was 36% and 13% of the cases were complicated by cerebrovascular accident. CE is a unique pathology that leads to acute myocardial infarction. It portends a high mortality rate and requires a high level of suspicion as symptoms may be misleading. Further research is needed in order to improve recognition and management and to lower associated mortality.

Rupture of sinus of Valsalva aneurysm: Two case reports and a concise review of the literature.

BACKGROUND: The rupture of sinus of Valsalva aneurysm (RSoVA) is a rare disorder that affects the integrity of the cardiovascular system, disrupting its dynamics and resulting in a variety of manifestations. In this report, we discuss two cases of RSoVA that we encountered and review similar cases reported in the literature. METHODS: literature review of reported cases of RSoVA in PubMed and Google Scholar. RESULTS: A total of 223 cases were found and the final analysis included 225 cases, of which 69% occurred in males and the mean age was 38.9 years. Dyspnea was the most common presenting symptom and 76% of the cases described continuous murmur on examination. The right sinus was affected in 61% of the cases and the fistula connected to the right chambers of the heart 73% of the time. CONCLUSION: RSoVA is a rare condition that is difficult to diagnose, it should be considered in the right context, particularly in young patients with symptoms of heart failure and the presence of continuous murmur on cardiac examination.

Myocardial Infarction Secondary to Blunt Chest Trauma.

Myocardial infarction (MI) following blunt chest trauma is rare, but potentially fatal. We treated a young patient for acute MI after falling chest-first on ice while playing hockey. Coronary artery bypass grafting (CABG) was performed after percutaneous stenting attempts were unsuccessful. By reviewing the related literature, we found 179 cases, the majority of which affected young males following road accidents. Left anterior descending artery was most frequently affected followed by right coronary artery particularly in their proximal thirds. Prior to the advent of emergent angioplasty for MI, conservative management was frequently pursued, whereas subsequently both stenting and CABG were performed as initial therapy. Several cases required CABG after the failure of stenting attempts. Trauma-associated MI is uncommon but should be suspected to be properly diagnosed and managed; the potential need for CABG requires that a cardiac surgeon be informed at the time of angiography to avoid possible delay in revascularization.

Effect of Disclosing Genetic Risk for Coronary Heart Disease on Information Seeking and Sharing: The MI-GENES Study (Myocardial Infarction Genes).

BACKGROUND: Whether disclosing genetic risk for coronary heart disease (CHD) to individuals influences information seeking and information sharing is not known. We hypothesized that disclosing genetic risk for CHD to individuals influences information seeking and sharing. METHODS AND RESULTS: The MI-GENES study (Myocardial Infarction Genes) randomized participants (n=203) aged 45 to 65 years who were at intermediate CHD risk based on conventional risk factors and not on statins to receive their conventional risk score alone or also a genetic risk score based on 28 variants. CHD risk was disclosed by a genetic counselor and then discussed with a physician. Surveys assessing information seeking were completed before and after risk disclosure. Information sharing was assessed post-disclosure. Six-month post-disclosure, genetic risk score participants were more likely than conventional risk score participants to visit a website to learn about CHD (odds ratio [OR], 4.88 [confidence interval (CI), 1.55-19.13]; P=0.01), use the internet for information about how genetic factors affect CHD risk (OR, 2.11 [CI, 1.03-4.47]; P=0.04), access their CHD risk via a patient portal (OR, 2.99 [CI, 1.35-7.04]; P=0.01), and discuss their CHD risk with others (OR, 3.13 [CI, 1.41-7.47]; P=0.01), particularly their siblings (OR, 1.92 [CI, 1.06-3.51]; P=0.03), extended family (OR, 3.8 [CI, 1.37-12.38]; P=0.01), coworkers (OR, 2.42 [CI, 1.09-5.76]; P=0.03), and primary care provider (PCP; OR, 2.00 [CI, 1.08-3.75]; P=0.03). CONCLUSIONS: Disclosure of a genetic risk score for CHD increased information seeking and sharing. CLINICAL TRIAL REGISTRATION: URL: https://clinicaltrials.gov/. Unique identifier: NCT01936675.

Disclosing Genetic Risk for Coronary Heart Disease: Attitudes Toward Personal Information in Health Records.

INTRODUCTION: Incorporating genetic risk information in electronic health records (EHRs) will facilitate implementation of genomic medicine in clinical practice. However, little is known about patients' attitudes toward incorporation of genetic risk information as a component of personal health information in EHRs. This study investigated whether disclosure of a genetic risk score (GRS) for coronary heart disease influences attitudes toward incorporation of personal health information including genetic risk in EHRs. METHODS: Participants aged 45-65 years with intermediate 10-year coronary heart disease risk were randomized to receive a conventional risk score (CRS) alone or with a GRS from a genetic counselor, followed by shared decision making with a physician using the same standard presentation and information templates for all study participants. The CRS and GRS were then incorporated into the EHR and made accessible to both patients and physicians. Baseline and post-disclosure surveys were completed to assess whether attitudes differed by GRS disclosure. Data were collected from 2013 to 2015 and analyzed in 2015-2016. RESULTS: GRS and CRS participants reported similar positive attitudes toward incorporation of genetic risk information in the EHR. Compared with CRS participants, participants with high GRS were more concerned about the confidentiality of genetic risk information (OR=3.67, 95% CI=1.29, 12.32, p=0.01). Post-disclosure, frequency of patient portal access was associated with positive attitudes. CONCLUSIONS: Participants in this study of coronary heart disease risk disclosure overall had positive attitudes toward incorporation of genetic risk information in EHRs, although those who received genetic risk information had concerns about confidentiality.

Painless Aortic Dissection.

Painless aortic dissection (PAoD) has been previously linked to poor outcomes. We recently encountered a case of a patient with PAoD presenting with dyspnea; the clue to diagnosis was the presence of a loud aortic diastolic murmur. A systematic review of the literature revealed 86 other cases, 62% of which occurred in men with a mean age of 65 years. Left-sided neurologic deficits were the most common presentation, followed by dyspnea and bilateral lower extremity deficits. Pulse asymmetry was found in 53% of patients, as 29% had right-left asymmetry and 24% had upper-lower asymmetry. Cumulatively, 88% of the cases were type A dissection and 51% of the patients died. Erroneous application of fibrinolysis and anticoagulation occurred in multiple instances. PAoD is rare but potentially fatal; a high index of suspicion and a thorough cardiovascular examination are needed to establish the diagnosis before applying possible harmful interventions such as fibrinolysis, vasodilation or anticoagulation.

Shared decision-making following disclosure of coronary heart disease genetic risk: results from a randomized clinical trial.

Whether disclosure of genetic risk for coronary heart disease (CHD) influences shared decision-making (SDM) regarding use of statins to reduce CHD risk is unknown. We randomized 207 patients, age 45-65 years, at intermediate CHD risk, and not on statins, to receive the 10-year risk of CHD based on conventional risk factors alone (n=103) or in combination with a genetic risk score (n=104). A genetic counselor disclosed this information followed by a physician visit for SDM regarding statin therapy. A novel decision aid was used in both encounters to disclose the CHD risk estimates and facilitate SDM regarding statin use. Patients reported their decision quality and physician visit satisfaction using validated surveys. There were no statistically significant differences between the two groups in the SDM score, satisfaction with the clinical encounter, perception of the quality of the discussion or of participation in decision-making and physician visit satisfaction scores. Quantitative analyses of a random subset of 80 video-recorded encounters using the OPTION5 scale also showed no significant difference in SDM between the two groups. Disclosure of CHD genetic risk using an electronic health record-linked decision aid did not adversely affect SDM or patients' satisfaction with the clinical encounter. TRIAL REGISTRATION NUMBER: NCT01936675; Results.

Plasma Osteopontin Levels and Adverse Cardiovascular Outcomes in the PEACE Trial.

Osteopontin (OPN) is a secreted glycophosphoprotein that has a role in inflammation, immune response and calcification. We hypothesized that plasma OPN levels are associated with adverse cardiovascular outcomes in patients with stable coronary artery disease (CAD) and preserved ejection fraction (EF) enrolled in the PEACE trial. We measured plasma OPN levels at baseline in 3567 CAD patients (mean age 64.5 ± 8.1 years, 81% men) by a sandwich chemiluminescent assay (coefficient of variation = 4.1%). OPN levels were natural log (Ln) transformed prior to analyses. We assessed whether Ln OPN levels were associated with the composite primary endpoint of cardiovascular death, non-fatal myocardial infarction and hospitalization for heart failure using multiple event multivariable Cox proportional hazards regression. Adjustment was performed for: (a) age and sex; (b) additional potential confounders; and (c) a parsimonious set of statistically significant 10 variates. During a median follow-up of 4.8 years, 416 adverse cardiovascular outcomes occurred in 366 patients. Ln OPN was significantly associated with the primary endpoint; HR (95% CI) = 1.56 (1.27, 1.92); P <0.001, and remained significant after adjustment for age and sex [1.31 (1.06, 1.61); P = 0.01] and after adjustment for relevant covariates [1.24 (1.01, 1.52); P = 0.04]. In a secondary analysis of the individual event types, Ln OPN was significantly associated with incident hospitalization for heart failure: HR (95% CI) = 2.04 (1.44, 2.89); P <0.001, even after adjustment for age, sex and additional relevant covariates. In conclusion, in patients with stable CAD and preserved EF on optimal medical therapy, plasma OPN levels were independently associated with the composite incident endpoint of adverse cardiovascular outcomes as well as incident hospitalization for heart failure.