World Heart Federation Roadmap for Secondary Prevention of Cardiovascular Disease: 2023 Update.

Background: Secondary prevention lifestyle and pharmacological treatment of atherosclerotic cardiovascular disease (ASCVD) reduce a high proportion of recurrent events and mortality. However, significant gaps exist between guideline recommendations and usual clinical practice. Objectives: Describe the state of the art, the roadblocks, and successful strategies to overcome them in ASCVD secondary prevention management. Methods: A writing group reviewed guidelines and research papers and received inputs from an international committee composed of cardiovascular prevention and health systems experts about the article's structure, content, and draft. Finally, an external expert group reviewed the paper. Results: Smoking cessation, physical activity, diet and weight management, antiplatelets, statins, beta-blockers, renin-angiotensin-aldosterone system inhibitors, and cardiac rehabilitation reduce events and mortality. Potential roadblocks may occur at the individual, healthcare provider, and health system levels and include lack of access to healthcare and medicines, clinical inertia, lack of primary care infrastructure or built environments that support preventive cardiovascular health behaviours. Possible solutions include improving health literacy, self-management strategies, national policies to improve lifestyle and access to secondary prevention medication (including fix-dose combination therapy), implementing rehabilitation programs, and incorporating digital health interventions. Digital tools are being examined in a range of settings from enhancing self-management, risk factor control, and cardiac rehab. Conclusions: Effective strategies for secondary prevention management exist, but there are barriers to their implementation. WHF roadmaps can facilitate the development of a strategic plan to identify and implement local and national level approaches for improving secondary prevention.

Clinical predictors of right ventricular dysfunction and association with adverse outcomes in peripartum cardiomyopathy.

AIMS: We sought to identify factors associated with right ventricular (RV) dysfunction and elevated pulmonary artery systolic pressure (PASP) and association with adverse outcomes in peripartum cardiomyopathy (PPCM). METHODS AND RESULTS: We conducted a multi-centre cohort study to identify subjects with PPCM with the following criteria: left ventricular ejection fraction (LVEF) < 40%, development of heart failure within the last month of pregnancy or 5 months of delivery, and no other identifiable cause of heart failure with reduced ejection fraction. Outcomes included a composite of (i) major adverse events (need for extracorporeal membrane oxygenation, ventricular assist device, orthotopic heart transplantation, or death) or (ii) recurrent heart failure hospitalization. RV function was obtained from echocardiogram reports. In total, 229 women (1993-2017) met criteria for PPCM. Mean age was 32.4 ± 6.8 years, 28% were of African descent, 50 (22%) had RV dysfunction, and 38 (17%) had PASP ≥ 30 mmHg. After a median follow-up of 3.4 years (interquartile range 1.0-8.8), 58 (25%) experienced the composite outcome of adverse events. African descent, family history of cardiomyopathy, LVEF, and PASP were significant predictors of RV dysfunction. Using Cox proportional hazards models, we found that women with RV dysfunction were three times more likely to experience the adverse composite outcome: hazard ratio 3.21 (95% confidence interval: 1.11-9.28), P = 0.03, in a multivariable model adjusting for age, race, body mass index, preeclampsia, hypertension, diabetes, kidney disease, and LVEF. Women with PASP ≥ 30 mmHg had a lower probability of survival free from adverse events (log-rank P = 0.04). CONCLUSIONS: African descent and family history of cardiomyopathy were significant predictors of RV dysfunction. RV dysfunction and elevated PASP were significantly associated with a composite of major adverse cardiac events. This at-risk group may prompt closer monitoring or early referral for advanced therapies.

Proprotein convertase subtilisn/kexin type 9 inhibitors and small interfering RNA therapy for cardiovascular risk reduction: A systematic review and meta-analysis.

BACKGROUND: Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of mortality worldwide. Atherosclerosis occurs due to accumulation of low-density lipoprotein cholesterol (LDL-c) in the arterial system. Thus, lipid lowering therapy is essential for both primary and secondary prevention. Proprotein convertase subtilisn/kexin type 9 (PCSK9) inhibitors (Evolocumab, Alirocumab) and small interfering RNA (siRNA) therapy (Inclisiran) have been demonstrated to lower LDL-c and ASCVD events in conjunction with maximally tolerated statin therapy. However, the degree of LDL-c reduction and the impact on reducing major adverse cardiac events, including their impact on mortality, remains unclear. OBJECTIVE: The purpose of this study is to examine the effects of PCSK9 inhibitors and small interfering RNA (siRNA) therapy on LDL-c reduction and major adverse cardiac events (MACE) and mortality by conducting a meta-analysis of randomized controlled trials. METHODS: Using Pubmed, Embase, Cochrane Library and clinicaltrials.gov until April 2023, we extracted randomized controlled trials (RCTs) of PCSK9 inhibitors (Evolocumab, Alirocumab) and siRNA therapy (Inclisiran) for lipid lowering and risk of MACE. Using random-effects models, we pooled the relative risks and 95% CIs and weighted least-squares mean difference in LDL-c levels. We estimated odds ratios with 95% CIs among MACE subtypes and all-cause mortality. Fixed-effect model was used, and heterogeneity was assessed using the I2 statistic. RESULTS: In all, 54 studies with 87,669 participants (142,262 person-years) met criteria for inclusion. LDL-c percent change was reported in 47 studies (n = 62,634) evaluating two PCSK9 inhibitors and siRNA therapy. Of those, 21 studies (n = 41,361) included treatment with Evolocumab (140mg), 22 (n = 11,751) included Alirocumab (75mg), and 4 studies (n = 9,522) included Inclisiran (284mg and 300mg). Compared with placebo, after a median of 24 weeks (IQR 12-52), Evolocumab reduced LDL-c by -61.09% (95% CI: -64.81, -57.38, p<0.01) and Alirocumab reduced LDL-c by -46.35% (95% CI: -51.75, -41.13, p<0.01). Inclisiran 284mg reduced LDL-c by -54.83% (95% CI: -59.04, -50.62, p = 0.05) and Inclisiran 300mg reduced LDL-c by -43.11% (95% CI: -52.42, -33.80, p = 0.01). After a median of 8 months (IQR 6-15), Evolocumab reduced the risk of myocardial infarction (MI), OR 0.72 (95% CI: 0.64, 0.81, p<0.01), coronary revascularization, 0.77 (95% CI: 0.70, 0.84, p<0.01), stroke, 0.79 (95% CI: 0.66, 0.94, p = 0.01) and overall MACE 0.85 (95% CI: 0.80, 0.89, p<0.01). Alirocumab reduced MI, 0.57 (0.38, 0.86, p = 0.01), cardiovascular mortality 0.35 (95% CI: 0.16, 0.77, p = 0.01), all-cause mortality 0.60 (95% CI: 0.43, 0.84, p<0.01), and overall MACE 0.35 (0.16, 0.77, p = 0.01). CONCLUSION: PCSK9 inhibitors (Evolocumab, Alirocumab) and siRNA therapy (Inclisiran) significantly reduced LDL-c by >40% in high-risk individuals. Additionally, both Alirocumab and Evolocumab reduced the risk of MACE, and Alirocumab reduced cardiovascular and all-cause mortality.

Lithium-Induced Bradycardia and Cardiomyopathy in a Patient With Bipolar Disorder and Paranoid Schizophrenia.

Lithium is primarily known to cause neurological and gastrointestinal side effects, however, cardiac effects have been rarely reported. We present a unique case of lithium cardiotoxicity causing bradyarrhythmia and cardiomyopathy. A 68-year-old man with a history of paranoid schizophrenia and bipolar disorder presented with altered mental status. On examination, the patient was lethargic, afebrile, with dry oral mucosa, and a regular pulse of 42 bpm. Labs revealed acute kidney injury and elevated lithium levels. Electrocardiogram (ECG) revealed a junctional escape rhythm with a right bundle morphology. Lithium toxicity was strongly suspected in the setting of raised serum lithium levels, decreased oral intake and acute kidney injury. The patient was found to have lithium-induced junctional bradycardia. Transvenous pacing was not indicated as the patient responded to fluids and atropine and had no severe hemodynamic compromise. As his serum lithium levels decreased, the bradycardia gradually improved. His echocardiogram revealed moderate left ventricular systolic dysfunction. Workup of cardiomyopathies was negative: no obstructive coronary artery disease; viral panel, and autoimmune markers were unremarkable. Thus, his cardiomyopathy was attributed to lithium toxicity. Lithium cardiotoxicity may manifest as arrhythmias and/or cardiomyopathy. Clinicians should have a high index of suspicion for lithium cardiotoxicity due to the narrow therapeutic range of lithium.

Physical and Psychological Outcomes of Patients Undergoing Traditional Cardiac Rehabilitation and Intensive Cardiac Rehabilitation.

PURPOSE: Both traditional cardiac rehabilitation (TCR) and intensive cardiac rehabilitation (ICR) have proven benefits for patients with cardiovascular disease. The aim of this study was to compare ICR versus TCR on cardiac rehabilitation (CR) outcomes in patients with cardiovascular disease. METHODS: In a retrospective cohort study of 970 patients (n = 251, ICR; n = 719, TCR) who were referred for CR between January 2018 and December 2019, 693 (71.4%) patients completed it. The TCR sessions were 90 min (60-min exercise) three times/wk for 12 wk, while ICR sessions were 4 hr (60-min exercise) two times/wk for 9 wk. Primary endpoints were change in cardiorespiratory fitness (CRF) (by difference in exercise prescription metabolic equivalents [METs] between the last session and the average of the second and third sessions), anxiety (Generalized Anxiety Disorder-7) scores, percent depression (Patient Health Questionnaire-9 or Center for Epidemiologic Studies Depression Scale) scores, and health status (36-item Short Form Health Survey physical and mental composite scores). Linear regression adjusted for imbalanced baseline characteristics (age, race, and diagnosis of angina). RESULTS: Of the 693 patients who completed CR (ICR = 204/251 [81%] vs TCR = 489/719 [68%], P < .01), mean age was 66 yr and 31% were female. Patients in TCR had a higher improvement in CRF (CR session METs: ICR +1.5 ± 1.2 vs TCR +1.9 ± 1.5, P < .01) but no difference in health status scores. Conversely, patients in ICR had more reduction in anxiety scores (-2 ± 4 vs -1 ± 3, P < .01) and percent reduction in depression scores (-8.3 ± 13.7% vs -5.0 ± 11.7%, P < .01) than patients in TCR. CONCLUSIONS: Patients in TCR had higher improvement in CRF while patients in ICR had higher improvement in anxiety and depression scores.

NT-proBNP and predictors of event free survival and left ventricular systolic function recovery in peripartum cardiomyopathy.

OBJECTIVE: To determine predictors of adverse outcomes in peripartum cardiomyopathy (PPCM). METHODS AND RESULTS: We conducted a multi-center cohort study across four centers to identify subjects with PPCM with the following criteria: LVEF <40%, development of heart failure within the last month of pregnancy or within 5 months of delivery and no other identifiable cause of heart failure with reduced ejection fraction. Outcomes included 1) survival free from major adverse events (need for extra-corporeal membrane oxygenation, ventricular assist device, orthotopic heart transplantation or death) and 2) LVEF recovery ≥ 50%. Using a univariate logistic regression analysis, we identified significant clinical predictors of these outcomes, which were then used to create multivariable models. NT-proBNP at the time of diagnosis was examined both as a continuous variable (log transformed) in logistic regression and as a dichotomous variable (values above and below the median) using the log-rank test. In all, 237 women (1993 to 2017) with 736.4 person-years of follow-up, met criteria for PPCM. Participants had a mean age of 32.4 ± 6.7 years, mean BMI 30.6 ± 7.8 kg/m2; 63% were White. After median follow-up of 3.6 years (IQR 1.1-7.8), 113 (67%) had LVEF recovery, and 222 (94%) had survival free from adverse events. Significant predictors included gestational age, gravidity, systolic blood pressure, smoking, heart rate, initial LVEF, and diuretic use. In a subset of 110 patients with measured NTproBNP levels, we found a higher event free survival for women with NTproBNP <2585 pg/ml (median) as compared to women with NTproBNP ≥2585 pg/ml (log-rank test p-value 0.018). CONCLUSION: Gestational age, gravidity, current or past tobacco use, systolic blood pressure, heart rate, initial LVEF and diuretic requirement at the time of diagnosis were associated with survival free from adverse events and LVEF recovery. Initial NT-proBNP was significantly associated with event free survival.

Cardiovascular Outcomes of Patients Referred to Home Based Cardiac Rehabilitation.

BACKGROUND: Home Based Cardiac Rehabilitation (HBCR) has been considered a reasonable alternative to Center-based Cardiac Rehabilitation (CBCR) in patients with established cardiovascular disease, especially in the midst of COVID-19 pandemic. However, the long-term cardiovascular outcomes of patients referred to HBCR remains unknown. OBJECTIVES: To compare outcomes of patients who were referred and attended HBCR vs patients referred but did not attend HBCR (Non-HBCR). METHODS: We performed a retrospective study of 269 patients referred to HBCR at Providence Veterans Affairs Medical Center (PVAMC). From November 2017 to March 2020, 427 patients were eligible and referred for Cardiac Rehabilitation (CR) at PVAMC. Of total patients, 158 patients were referred to CBCR and 269 patients to HBCR based on patient and/or clinician preference. The analysis of outcomes was focused on HBCR patients. We compared outcomes of patients who were referred and attended HBCR vs patients referred but did not attend HBCR (Non-HBCR) from 3 to 12 months of the referral date. HBCR consisted of face-to-face entry exam with exercise prescription, weekly phone calls for education and exercise monitoring, with adjustments where applicable, for 12-weeks and an exit exam. Primary outcome was composite of all-cause mortality and hospitalizations. Secondary outcomes were all-cause hospitalization, all-cause mortality and cardiovascular hospitalizations, separately. We used cox proportional methods to calculate hazard ratios (HR) and 95% CI. We adjusted for imbalanced characteristics at baseline: smoking, left ventricular ejection fraction and CABG status. RESULTS: A total of 269 patients (mean age: 72, 98% Male) were referred to HBCR, however, only 157 (58%) patients attended HBCR. The primary outcome occurred in 30 patients (19.1%) in the HBCR group and 30 patients (30%) in the Non-HBCR group (adjusted HR=0.56, CI 0.33-0.95, P=.03). All-cause mortality occurred in 6.4% of patients in the HBCR group and 13% patients in the Non-HBCR group 3 to 12 months after HBCR referral (adjusted HR=0.43, CI 0.18-1.0, P= .05). There was no difference in cardiovascular hospitalizations (HBCR: 5.7% vs Non-HBCR: 10%, adjusted HR 0.57, CI 0.22-1.4, P= .23) or all cause hospitalizations at 3 to 12 months between the groups (HBCR: 12.7% vs Non-HBCR: 21%, adjusted HR 0.53, CI 0.28-1.01, P= .05). CONCLUSION: Completion of HBCR among referred patients was associated with a lower risk of the combined all-cause mortality and all-cause hospitalizations up to 12 months. Based on the outcomes, HBCR is a reasonable option that can improve access to CR for patients who are not candidates of or cannot attend CBCR. Randomized-controlled studies are needed to confirm these findings.

Mobile Technology Improves Adherence to Cardiac Rehabilitation: A Propensity Score-Matched Study.

Background Despite its established effectiveness, adherence to cardiac rehabilitation remains suboptimal. The purpose of our study is to examine whether mobile technology improves adherence to cardiac rehabilitation and other outcomes. Methods and Results We identified all enrollees of the cardiac rehabilitation program at Boston Medical Center from 2016 to 2019 (n=830). Some enrollees used a mobile technology application that provided a customized list of educational content in a progressive manner, used the patient's smartphone accelerometer to provide daily step counts, and served as a 2-way messaging system between the patient and program staff. Adherence to cardiac rehabilitation was defined as the number of attended sessions and completion of the program. Enrollees had a mean age of 59 years; 32% were women, and 42% were Black. Using 3:1 propensity matching for age, sex, race/ethnicity, education, smoking status, transportation time, diagnosis, and baseline depression survey score, we evaluated change in exercise capacity, weight, functional capacity, and nutrition scores. Those in the mobile technology group (n=114) attended a higher number of prescribed sessions (mean 28 versus 22; relative risk, 1.17; 95% CI, 1.04-1.32; P=0.009), were 1.8 times more likely to complete the cardiac rehabilitation program (P=0.01), and had a slightly greater weight loss (pounds) following rehabilitation (-1.71; 95% CI, -0.30 to -3.11; P=0.02) as compared with those in the standard group (n=213); other outcomes were similar between the groups. Conclusions In a propensity-matched, racially diverse population, we found that adjunctive use of mobile technology is significantly associated with improved adherence to cardiac rehabilitation and number of attended sessions.

Sugar-Sweetened Beverage Consumption and Calcified Atherosclerotic Plaques in the Coronary Arteries: The NHLBI Family Heart Study.

BACKGROUND: Sugar-sweetened beverage (SSB) intake is associated with higher risk of weight gain, diabetes, hypertension, cardiovascular disease, and cardiovascular mortality. However, the association of SSB with subclinical atherosclerosis in the general population is unknown. OBJECTIVE: Our primary objective was to investigate the association between SSB intake and prevalence of atherosclerotic plaque in the coronary arteries in The National Heart, Lung, and Blood Institute (NHLBI) Family Heart Study. METHODS: We studied 1991 participants of the NHLBI Family Heart Study without known coronary heart disease. Intake of SSB was assessed through a semi-quantitative food frequency questionnaire. Coronary artery calcium (CAC) was measured by cardiac Computed Tomography (CT) and prevalent CAC was defined as an Agatston score ≥100. We used generalized estimating equations to calculate adjusted prevalence ratios of CAC. A sensitivity analysis was also performed at different ranges of cut points for CAC. RESULTS: Mean age and body mass index (BMI) were 55.0 years and 29.5 kg/m2, respectively, and 60% were female. In analysis adjusted for age, sex, BMI, smoking, alcohol use, physical activity, energy intake, and field center, higher SSB consumption was not associated with higher prevalence of CAC [prevalence ratio (95% confidence interval) of: 1.0 (reference), 1.36 (0.70-2.63), 1.69 (0.93-3.09), 1.21 (0.69-2.12), 1.05 (0.60-1.84), and 1.58 (0.85-2.94) for SSB consumption of almost never, 1-3/month, 1/week, 2-6/week, 1/day, and ≥2/day, respectively (p for linear trend 0.32)]. In a sensitivity analysis, there was no evidence of association between SSB and prevalent CAC when different CAC cut points of 0, 50, 150, 200, and 300 were used. CONCLUSIONS: These data do not provide evidence for an association between SSB consumption and prevalent CAC in adult men and women.

Nut consumption, risk of cardiovascular mortality, and potential mediating mechanisms: The Women's Health Study.

BACKGROUND: The link between nut consumption and cardiovascular (CV) mortality remains unclear. OBJECTIVE: to examine whether nut consumption is associated with CV mortality and estimate the proportion of reduced risk of CV mortality explained by intermediate factors. METHODS: We studied 39,167 women from the Women's Health Study; 28,034 provided blood samples. Nut consumption was self-reported at baseline and at follow-up using a food frequency questionnaire. Our primary outcome was cardiovascular death, which was ascertained via medical records, confirmed with the national death index and death certificates. RESULTS: During a mean follow-up of 19 years, 959 CV deaths occurred. In a multivariable Cox regression model adjusting for age, body mass index, smoking, alcohol use, physical activity, postmenopausal status, marital status, family history of premature myocardial infarction and the alternate healthy eating index score, hazard ratios for CV mortality were 0.93 (0.76-1.14) for nut consumption of 1-3 times/month, 0.84 (0.69-1.01) for nut intake of 1 time/week, and 0.73 (0.61-0.87) for nut consumption of ≥2 times/week when compared to women who did not consume nuts (p = 0.0004). LDL and total cholesterol accounted for about 19%, HbA1c 18% and all mediating factors together accounted for about 6.6% of the lower risk of CV mortality for those who consumed nuts ≥2 times/week. For the secondary outcome of CV events, although the effect was noted to be in the same direction with increasing nut consumption associated with lower risk of CV events, it was not statistically significant (p = 0.07). CONCLUSION: This study suggests that nut consumption is inversely associated with cardiovascular mortality in women. Lipids, inflammatory markers and glucose metabolism account for a modest proportion of the lowered CV mortality observed with nut consumption, assuming a causal nut-CV mortality association.

Walking pace is inversely associated with risk of death and cardiovascular disease: The Physicians' Health Study.

BACKGROUND: Walking pace is increasingly being used to assess functional status in ambulatory settings. METHODS: We conducted a prospective analysis within the Physicians' Health Study to examine whether walking pace is associated with mortality and incident cardiovascular disease (fatal or nonfatal myocardial infarction, coronary artery bypass grafting and percutaneous transluminal coronary angioplasty). Participants included 21,919 male physicians with a mean age of 67.8 ±â€¯9.0 years. RESULTS: After a median follow-up of 9.4 years (IQR: 7.9-10.3), 3906 deaths and 2487 incident CVD events occurred. In a multivariable Cox proportional hazards model adjusting for age, body mass index, smoking, exercise frequency, and prevalent hypertension, diabetes mellitus, heart failure, peripheral vascular disease, cancer, and total weekly walking time, hazard ratios for mortality were 0.72 (95% CI: 0.64-0.81) for walking pace of 2-2.9mph, 0.63 (95% CI: 0.55-0.73) for walking pace of 3-3.9mph and 0.63 (95% CI: 0.48-0.83) for walking pace of ≥4mph compared to the group that reported not walking regularly (p trend <0.0001). Similar findings were observed for incident CVD: HRs were 0.88 (95% CI: 0.75-1.03) for a walking pace of 2-2.9mph, 0.75 (95% CI: 0.63-0.89) for a walking pace of 3-3.9mph and 0.70 (0.53-0.94) for a walking pace of ≥4mph compared to the group that reported not walking regularly (p trend 0.0001). These associations persisted after excluding those who exercised regularly. CONCLUSION: We found that walking pace is inversely associated with risk of mortality and CVD among US male physicians.

Serial sodium values and adverse outcomes in heart failure with preserved ejection fraction.

OBJECTIVE: The purpose of our study is to examine whether serial measurements of serum sodium values after diagnosis identify a higher-risk subset of patients with heart failure with preserved ejection fraction. METHODS: We identified 50,932 subjects with HFpEF with 759,577 recorded sNa measurements (mean age 72 ±â€¯11 years) using a validated algorithm in the VA national database from 2002 to 2012. We examined the association of repeated measures of sNa with mortality using a multivariable Cox proportional hazards model. RESULTS: After a median follow-up of 2.9 years (IQR: 1.2-5.4), 19,011 deaths occurred. After adjusting for age, sex, race, BMI, glomerular filtration rate, potassium, coronary artery disease, hypertension, hyperlipidemia, atrial fibrillation, pulmonary disease, diabetes, anemia, and medications, we found J-shaped associations of serum sodium with mortality. HRs for all-cause mortality were 2.48 (95% CI: 2.38-2.60) for the sNA 115.00-133.99 category; and 1.40 (95% CI: 1.35-1.46) for the sNA 143.00-175.00 category compared to the 137.01-140.99 category (ref). We used generalized estimating equation-based negative binomial regression to compute the incidence density ratios (IDR) to examine days hospitalized for heart failure and for all causes. There were a total of 1,275,614 days of all-cause hospitalization and 104,006 days of heart-failure hospitalization. The IDRs for the lowest sNA group were 2.03 (95% CI: 1.90-2.18) for all-cause hospitalization and 1.73 (95% CI: 1.39-2.16) for heart-failure hospitalization. CONCLUSIONS: Our findings suggest that monitoring of serum sodium values during longitudinal follow-up can identify HFpEF patients at risk of adverse outcomes.

A phenotyping algorithm to identify acute ischemic stroke accurately from a national biobank: the Million Veteran Program.

BACKGROUND: Large databases provide an efficient way to analyze patient data. A challenge with these databases is the inconsistency of ICD codes and a potential for inaccurate ascertainment of cases. The purpose of this study was to develop and validate a reliable protocol to identify cases of acute ischemic stroke (AIS) from a large national database. METHODS: Using the national Veterans Affairs electronic health-record system, Center for Medicare and Medicaid Services, and National Death Index data, we developed an algorithm to identify cases of AIS. Using a combination of inpatient and outpatient ICD9 codes, we selected cases of AIS and controls from 1992 to 2014. Diagnoses determined after medical-chart review were considered the gold standard. We used a machine-learning algorithm and a neural network approach to identify AIS from ICD9 codes and electronic health-record information and compared it with a previous rule-based stroke-classification algorithm. RESULTS: We reviewed administrative hospital data, ICD9 codes, and medical records of 268 patients in detail. Compared with the gold standard, this AIS algorithm had a sensitivity of 91%, specificity of 95%, and positive predictive value of 88%. A total of 80,508 highly likely cases of AIS were identified using the algorithm in the Veterans Affairs national cardiovascular disease-risk cohort (n=2,114,458). CONCLUSION: Our algorithm had high specificity for identifying AIS in a nationwide electronic health-record system. This approach may be utilized in other electronic health databases to accurately identify patients with AIS.

Prognostic Significance of Baseline Serum Sodium in Heart Failure With Preserved Ejection Fraction.

BACKGROUND: The purpose of this study was to evaluate the relationship between serum sodium at the time of diagnosis and long term clinical outcomes in a large national cohort of patients with heart failure with preserved ejection fraction. METHODS AND RESULTS: We studied 25 440 patients with heart failure with preserved ejection fraction treated at Veterans Affairs medical centers across the United States between 2002 and 2012. Serum sodium at the time of heart failure diagnosis was analyzed as a continuous variable and in categories as follows: low (115.00-134.99 mmol/L), low-normal (135.00-137.99 mmol/L), referent group (138.00-140.99 mmol/L), high normal (141.00-143.99 mmol/L), and high (144.00-160.00 mmol/L). Multivariable Cox regression and negative binomial regression were performed to estimate hazard ratios (95% confidence interval [CI]) and incidence density ratios (95% CI) for the associations of serum sodium with mortality and hospitalizations (heart failure and all-cause), respectively. The average age of patients was 70.8 years, 96.2% were male, and 14% were black. Compared with the referent group, low, low-normal, and high sodium values were associated with 36% (95% CI, 28%-44%), 6% (95% CI, 1%-12%), and 9% (95% CI, 1%-17%) higher risk of all-cause mortality, respectively. Low and low-normal serum sodium were associated with 48% (95% CI, 10%-100%) and 38% (95% CI, 8%-77%) higher risk of number of days of heart failure hospitalizations per year, and with 44% (95% CI, 32%-56%) and 18% (95% CI, 10%-27%) higher risk of number of days of all-cause hospitalizations per year, respectively. CONCLUSIONS: Both elevated and reduced serum sodium, including values currently considered within normal range, are associated with adverse outcomes in patients with heart failure with preserved ejection fraction.

Lack of Association Between Heart Failure and Incident Cancer.

BACKGROUND: Several recent studies have suggested an increased cancer risk among patients with heart failure (HF). However, these studies are constrained by limited size and follow-up, lack of comprehensive data on other health attributes, and adjudicated cancer outcomes. OBJECTIVES: This study sought to determine whether HF is associated with cancer incidence and cancer-specific mortality. METHODS: The study assembled a cohort from the Physicians' Health Studies I and II, 2 randomized controlled trials of aspirin and vitamin supplements conducted from 1982 to 1995 and from 1997 to 2011, respectively, that included annual health evaluations and determination of cancer and HF diagnoses. In the primary analysis, the study excluded participants with cancer or HF at baseline and performed multivariable-adjusted Cox models to determine the relationship between HF and cancer, modeling HF as a time-varying exposure. In a complementary analysis, the study used the landmark method and identified cancer-free participants at 70 years of age, distinguishing between those with and without HF, and likewise performed Cox regression. Sensitivity analyses were performed at 65, 75, and 80 years of age. RESULTS: Among 28,341 Physicians' Health Study participants, 1,420 developed HF. A total of 7,363 cancers developed during a median follow-up time of 19.9 years (25th to 75th percentile: 11.0 to 26.8 years). HF was not associated with cancer incidence in crude (hazard ratio: 0.92; 95% confidence interval: 0.80 to 1.08) or multivariable-adjusted analysis (hazard ratio: 1.05; 95% confidence interval: 0.86 to 1.29). No association was found between HF and site-specific cancer incidence or cancer-specific mortality after multivariable adjustment. Results were similar when using the landmark method at all landmark ages. CONCLUSIONS: HF is not associated with an increased risk of cancer among male physicians.

Television Viewing Time, Physical Activity, and Mortality Among African Americans.

BACKGROUND: Prolonged television viewing time, a marker of sedentary activity, is independently associated with increased all-cause mortality; however, this association has rarely been studied in African Americans. The objective of our study was to examine the association between television viewing time and mortality among African Americans by using data from the Jackson Heart Study (JHS). METHODS: We studied 5,289 participants from the JHS study who reported television viewing time (h/day) in the JHS baseline questionnaire from 2000 through 2004. Using multivariable Cox regression models adjusted for age, sex, smoking, alcohol use, physical activity, nutrition, prevalent coronary heart disease, chronic kidney disease, diabetes, and hypertension, we computed hazard ratios to examine the association between television viewing time (≤2 h/day, 2-4 h/day, and ≥4 h/day) and mortality. RESULTS: Participants had a mean age of 55 years, and 64% were women. After a median follow-up of 9.9 years (interquartile range, 9.0-10.7), 615 deaths occurred (data analysis conducted in 2017). Hazard ratios for mortality were 1.08 (0.86-1.37) for television time of 2 to 4 hours per day and 1.48 (95% CI: 1.19-1.83) for television time of greater than or equal to 4 hours per day when compared with those who watched television less than 2 hours per day (P trend = .002). When we restricted analyses to those who performed leisure-time activities, the hazard ratios for mortality were 1.10 (95% CI, 0.84-1.45) for television viewing of 2 to 4 hours per day and 1.45 (95% CI, 1.13-1.86) for more than 4 hours per day compared with the less than 2 hours per day. CONCLUSION: Our findings suggest that greater television viewing time, even among those who perform leisure-time physical activities, is associated with increased all-cause mortality among African Americans. Thus, it may serve as an indicator of a sedentary lifestyle with potential for intervention.

Serial Magnetic Resonance Imaging in Creutzfeldt-Jakob Disease: a Case Report and Literature Review.

Creutzfeldt-Jakob disease (CJD) is a rare, degenerative, invariably fatal brain disorder. CJD usually appears in later life and runs a rapid course. Typically, the onset of symptoms occurs about age 60 and about 90% of individuals die within one year. We report a case of 67-year-old male presented with progressive aphasia, confusion, dysphagia and inability to carry out activities of daily life (ADLs) over a period of three to four weeks. The patient had past medical history of chronic atrial fibrillation and hypertension. Prior to admission, the patient was treated for ischemic stroke of left basal ganglia but continued to have worsening encephalopathy. The spinal tap revealed a 14-3-3 protein level of thirteen times the upper limit of normal; electroencephalogram (EEG) showed a diffuse slowing of the background and periodic sharp waves with greater involvement of the left hemisphere. Diffusion-weighted imaging (DWI) magnetic resonance imaging (MRI) at the time of admission showed extensive signal abnormality in the basal ganglia bilaterally and in the cerebral cortex bilaterally, particularly over the left cerebral hemisphere. The persistence of the MRI findings over several weeks was concerning for spongiform encephalopathy. The probable diagnosis of Creutzfeldt-Jakob disease was made based on these imaging findings taken together with the patient's clinical signs and symptoms of a rapidly progressive encephalopathy. The patient was able to have some quality time with his family as the diagnosis was made earlier than perhaps otherwise and expired peacefully after comfort care measures were chosen. Serial MRI may serve as a clue to the early diagnosis of CJD and potentially provide a better quality of life for the patients.

Meta-Analysis of the Usefulness of Plasma Galectin-3 to Predict the Risk of Mortality in Patients With Heart Failure and in the General Population.

Galectin-3 is an emerging biomarker of myocardial fibrosis, inflammation, and immune response. We sought to examine the relation of plasma galectin-3 with cardiovascular (CVD) mortality, all-cause mortality, and incident heart failure (HF). We performed a literature search for all relevant publications using Ovid MEDLINE, Google Scholar, and other databases up to January 2016. Two reviewers independently extracted data and assessed risk of bias. We extracted hazard ratios (HRs) from regression models that adjusted for age, gender, race, body mass index, smoking, hypertension, hyperlipidemia, diabetes, natriuretic peptides, and renal function, when available. A total of 18 studies with 32,350 participants (323,090 person-years of follow-up) met criteria for analysis. The mean age was 57.3 years and 47.2% of participants were women, with a follow-up duration median of 5 years, interquartile range: 2.9 to 10 years. Of the 18 studies, 13 (72%) adjusted for N-terminal probrain natriuretic peptide and renal function in the multivariable adjusted models. Using a random-effects meta-analysis, we found an HR of 1.10 (95% CI 1.05 to 1.14) for all-cause mortality, 1.22 (95% CI 1.05 to 1.39) for CVD mortality, and 1.12 (95% CI 1.04 to 1.21) for HF risk for each 1 SD increase in galectin-3 level. In a subgroup analysis of CVD mortality, the HR was 1.44 (1.09 to 1.79) for patients with HF and 1.09 (0.91 to 1.27) for the general population. In conclusion, our results suggest that elevated plasma galectin-3 is associated with a higher risk of all-cause mortality, CVD mortality, and HF. It may add prognostic value beyond that provided by traditional CVD risk factors.

Facial Weakness, Diplopia, and Fever in a 31-Year-Old: An Atypical Case of Tuberculous Meningitis.

Tuberculous meningitis (TBM) is an infection of the central nervous system (CNS) meninges that carries high morbidity and mortality. It is important to recognize, as patients may present with atypical symptoms. We describe the case of a 31-year-old man with a history of diabetes who presented with a sub-acute onset of right-sided facial weakness and right gaze difficulty with diplopia. History revealed low-grade fever, right-sided headache, fatigue and moderate weight loss for the past several weeks. The patient did not report neck stiffness, rigidity, fever, chills or cough. The physical exam revealed sixth nerve palsy with a right Horner's syndrome. Magnetic resonance imaging (MRI) of the brain showed pachymeningeal enhancement. A spinal tap revealed elevated white blood cells (WBCs), glucose and protein; cerebrospinal fluid (CSF) culture showed Mycobacterium tuberculosis. The patient was diagnosed with TBM and treated with isoniazid, rifampin, pyrazinamide, ethambutol and vitamin B6 for 12 months. The timely diagnosis of TBM can be challenging due to a nonspecific clinical presentation. In patients with a sub-acute onset of headache, fever and meningeal signs, TBM should be considered in the differential. If suspected, treatment should be initiated immediately to prevent further neurological impairment and death.