Management and Treatment of Myocarditis in Athletes.

PURPOSE OF REVIEW: Myocarditis is an inflammation of the myocardium that can often be associated with cardiac dysfunction and arrhythmias, and is even one of the leading causes for sudden cardiac death (SCD) in athletes. This review aims to summarize the current evidence and treatment guidelines for the management of myocarditis in the active population. RECENT FINDINGS: Physical exertion is likely a trigger for dangerous arrythmias and further propagates myocardial damage in athletes with myocarditis. For this reason, abstinence from sports is a critical facet of management in the initial inflammatory period. The use of cardiac magnetic resonance imaging, specifically late gadolinium enhancement, to guide return to play decisions is becoming more common in clinical practice. SUMMARY: Establishing a stepwise approach for proper diagnosis and risk stratification, with an emphasis on contemporary cardiac magnetic resonance (CMR) imaging techniques, in myocarditis is critical. After a diagnosis of myocarditis is made, it is imperative for any athlete or highly active individual to refrain from physical exercise. Additionally, therapy for heart failure should be applied in cases of myocarditis with cardiac dysfunction. Undoubtedly, COVID 19, and its potential to cause myocarditis, is sure to change the landscape of management of this disease.

Synthetic psychoactive cathinones: hypothermia and reduced lethality compared to methamphetamine and methylenedioxymethamphetamine.

RATIONALE: Synthetic psychoactive cathinones (SPCs) are drugs with psychostimulant and entactogenic properties like methamphetamine (MA) and 3,4-methylenedioxymethamphetamine (MDMA). Despite clinical reports of human overdose, it remains to be determined if SPCs have greater propensity for adverse effects than MA or MDMA. OBJECTIVES: To determine whether the SPCs cathinone (CAT), methcathinone (MCAT), mephedrone (MMC), and methylenedioxypyrovalerone (MDPV) have lower LD50 values than MA or MDMA. METHODS: Male and female C57Bl/6J mice received single injections of one of 6 doses of a test drug (0-160 mg/kg IP). Temperature and behavioral observations were taken every 20 min for 2 h followed by euthanasia of surviving mice. Organs were weighed and evaluated for histopathological changes. RESULTS: LD50 values for MA and MDMA, 84.5 and 100.9 mg/kg respectively, were similar to previous observations. The LD50 for MMC was 118.8 mg/kg, but limited lethality was observed for other SPCs (CAT, MCAT, MDPV), so LD50 values could not be calculated. For all drugs, death was associated with seizure, when it was observed. Rather than hyperthermia, dose-dependent hypothermia was observed for MMC, MDPV, CAT, and MCAT. Contrary to initial expectations, none of the SPCs studied here had LD50 values lower than MA or MDMA. CONCLUSIONS: These data indicate that, under the conditions studied here: (1) SPCs exhibit less lethality than MA and MDMA; (2) SPCs impair thermoregulation; (3) effects of SPCs on temperature appear to be independent of effects on lethality.

Myocardial longitudinal strain, fitness, and heart failure risk factors in young adults.

AIMS: To investigate the relationship between fitness, heart failure (HF) risk factors (age, blood pressure, and obesity), and global/regional myocardial longitudinal strain in young adults undergoing stress testing. METHODS: Individuals 25-55 years old without any significant medical history, not taking medications, and with a normal maximal stress echocardiogram were eligible. Global and regional longitudinal strain (LS) was evaluated by 2D speckle tracking echocardiography. RESULTS: One hundred and seventy patients were included, of which 60% were males. The mean age was 43 years old, 49% had optimal blood pressure, and 30% were obese. On average, patients achieved 10.5 (3) METS, and the global LS was -19.9 (3.1) %. Reduced fitness was associated with decreased global longitudinal strain (GLS). Those in the top GLS quartile walked on average 1 minute and 21 seconds longer compared with the lowest quartile (P < .001). The effect of fitness on LS was preferential to the mid and apex, such that there was an apex-to-base gradient. Obesity was also independently associated with reduced GLS. However, the reduction in LS in obese individuals was more prominent at the base and mid-walls with relative sparing of the apex. Similar to fitness, aging was also associated with an increase in the apex-to-base gradient of LS. Furthermore, diastolic filling parameters correlated distinctively with regional LS. CONCLUSIONS: In young adults without cardiovascular disease, low fitness and obesity are independently associated with reduced left ventricular longitudinal strain. There is a differential effect of HF risk factors on regional longitudinal function.

Invasive Coronary Physiological Assessment in Symptomatic Middle-Aged Endurance Athletes

Despite the health benefits of routine exercise, coronary artery disease (CAD) is common among older competitive athletes and is an important cause of sudden cardiac death. Athletes with suspected or confirmed CAD routinely undergo conventional coronary angiography involving the performance of invasive coronary physiological assessment using the fractional flow reserve (FFR) or the instantaneous-wave free ratio (iFR). Data defining the role of invasive coronary physiological assessment, while robust in general clinical populations, are untested among older competitive athletes with CAD. The paper discusses the challenges and uncertainties surrounding the use of the FFR and iFR in this unique population with an emphasis on the need for future work to better define this approach

The effects of physical activity on cancer prevention, treatment and prognosis: A review of the literature.

INTRODUCTION: The World Health Organization has reported that approximately 35% of cancer-related deaths are attributed to modifiable risk factors. Among the most important risk factors amenable to modification are obesity and lack of physical activity. The purpose of this article is to review the current evidence of the benefits of physical activity in various types of cancer. METHODS: A PubMed search for the key words "physical activity and cancer" as well as "exercise and cancer" was used to identify all indexed publications on this topic for potential utilization in this review. One MET was defined as the amount of oxygen consumed while a person is sitting quietly and is about 3.5 mL O2/kg body weight/min. MET represents the ratio of the working metabolic rate to the resting metabolic rate. RESULTS: Routine physical activity was found to be associated with a reduced incidence of several of the most common malignancies, including colon, breast, lung, and endometrial cancer as well as many others. Physical activity also appears to reduce all-cause mortality and cancer-related mortality among patients with breast and colon cancer, and may improve the functional status and quality of life for these patients during cancer therapy. CONCLUSIONS: The benefits of physical activity in the prevention and progression of cancer patients are multiple. However, the strength of the available evidence is limited by the observational nature of most studies. Given the probable improvement in prevention, mortality, and quality of life with structured physical activity in different malignancies, it is important that healthcare providers discuss physical activity programs with their cancer patients. Larger randomized trials are recommended.

Developmental effects of trichloroacetate in Zebrafish embryos: Association with the production of superoxide anion.

To assess the developmental toxicity of trichloroacetate (TCA), zebrafish embryos were exposed to 8 to 48 mM of TCA and evaluated for developmental milestones from 8- to 144-hour postfertilization (hpf). All developmental toxicities are reported in this paper. Embryos were found to have developed edema in response to 16 to 48 mM of TCA exposure at 32- to 80-hpf, experienced delay in hatching success in response to 24 to 48 mM at 80-hpf. Lordosis was observed in developing embryos exposed to 40 to 48 mM at 55- to 144-hpf. The observed toxic effects of TCA exposure were found to be concentration and exposure period independent. Effects were found to be associated with increases in superoxide anion production, but these increases were also found to be concentration and time independent. TCA resulted in concentration-dependent increases in embryonic lethality at 144-hpf, with an LC50 determined to be 29.7 mM.

One-year experience with ex vivo lung perfusion: Preliminary results from a single center.

OBJECTIVE: To enlarge the donor pool for lung transplantation, an increasing number of extended criteria donor lungs are used. However, in more than 50% of multi-organ donors the lungs are not used. Ex vivo lung perfusion offers a unique possibility to evaluate and eventually recondition the injured donor lungs. The aim of our study was to assess the enlargement of the donor pool and the outcome with extended criteria donor lungs after ex vivo lung perfusion. PATIENTS AND METHODS: Data were prospectively collected in our lung transplant database. We compared the results of lung transplants after ex vivo lung perfusion with those after conventional cold static preservation. In total, 11 extended criteria donor lungs processed with ex vivo lung perfusion and 41 cold static preservation lungs transplanted consecutively between May 2016 and May 2017 were evaluated. Normothermic ex vivo lung perfusion was performed according to the Toronto protocol for 4 h. Cold static preservation lungs were stored in low-potassium dextran solution. RESULTS: Ex vivo lung perfusion lungs before procurement had significantly lower PaO2/FiO2 (P/F) ratios and more X-ray abnormalities. There were no statistically significant differences for pre-donation ventilation time, smoking history, or sex. After reconditioning with ex vivo lung perfusion, 9 out of 11 processed lungs were considered suitable and successfully transplanted. The mean postoperative ventilation time and in-hospital stay were not significantly different in ex vivo lung perfusion and cold static preservation recipients. CONCLUSION: Ex vivo lung perfusion can safely be used in the evaluation of lungs initially considered not suitable for transplantation. The primary outcome was not negatively affected and normothermic ex vivo lung perfusion is a useful tool to increase the usage of potentially transplantable lungs.

Effect of high-dose oral multivitamins and minerals in participants not treated with statins in the randomized Trial to Assess Chelation Therapy (TACT).

IMPORTANCE: In a prespecified subgroup analysis of participants not on statin therapy at baseline in the TACT, a high-dose complex oral multivitamins and multimineral regimen was found to have a large unexpected benefit compared with placebo. The regimen tested was substantially different from any vitamin regimen tested in prior clinical trials. OBJECTIVE: To explore these results, we performed detailed additional analyses of participants not on statins at enrollment in TACT. DESIGN: TACT was a factorial trial testing chelation treatments and a 28-component high-dose oral multivitamins and multiminerals regimen versus placebo in post-myocardial infarction (MI) patients 50 years or older. PARTICIPANTS: There were 460 (27%) of 1,708 TACT participants not taking statins at baseline, 224 (49%) were in the active vitamin group and 236 (51%) were in the placebo group. SETTING: Patients were enrolled at 134 sites around the United States and Canada. INTERVENTION: Daily high-dose oral multivitamins and multiminerals (6 tablets, active or placebo). MAIN OUTCOME: The primary end point of TACT was time to the first occurrence of any component of the composite end point: all-cause mortality, MI, stroke, coronary revascularization, or hospitalization for angina. RESULTS: The primary end point occurred in 137 nonstatin participants (30%), of which 51 (23%) of 224 were in the active group and 86 (36%) of 236 were taking placebo (hazard ratio, 0.62; 95% confidence interval, 0.44-0.87; P=.006). Results in the key TACT secondary end point, a combination of cardiovascular mortality, stroke, or recurrent MI, was consistent in favoring the active vitamin group (hazard ratio, 0.46; 95% confidence interval, 0.28-0.75; P=.002). Multiple end point analyses were consistent with these results. CONCLUSION AND RELEVANCE: High-dose oral multivitamin and multimineral supplementation seem to decrease combined cardiac events in a stable, post-MI population not taking statin therapy at baseline. These unexpected findings are being retested in the ongoing TACT2.

Left Atrial Size and Heart Failure Hospitalization in Patients with Diastolic Dysfunction and Preserved Ejection Fraction.

CONTEXT: Heart failure with preserved ejection fraction (HFpEF) is a clinical syndrome associated with diastolic function abnormalities. It remains unclear which factors, if any, can predict the transition from asymptomatic diastolic dysfunction to an overt symptomatic phase. MATERIALS AND METHODS: Patients hospitalized with suspected heart failure between January 2012 and November 2014 with a transthoracic echocardiogram demonstrating preserved systolic function were screened (n = 425). Patients meeting the American College of Cardiology Foundation/American Heart Association definition for HFpEF (n = 40) were matched in a 1:1 fashion to individuals admitted for hypertensive urgency with diastolic dysfunction and neither pulmonary edema nor history of heart failure (n = 40). The clinical records and echocardiograms of all eighty patients included in this retrospective study were reviewed. RESULTS: Patients with HFpEF had higher body mass index (BMI), creatinine, beta-blocker use, and Grade 2 diastolic dysfunction when compared to the hypertensive control population. Echocardiographic analysis demonstrated higher right ventricular systolic pressures, left ventricular mass index, E/A, and E/e' in patients with HFpEF. Similarly, differences were observed in most left atrial (LA) parameters including larger LA maximum and minimum volume indices, as well as smaller LA-emptying fractions in the heart failure group. Multivariate logistic regression analysis revealed LA minimum volume index (odds ratio [OR]: 1.23 [1.09-1.38], P = 0.001) to have the strongest association with heart failure hospitalization after adjustment for creatinine (OR: 7.09 [1.43-35.07], P = 0.016) and BMI (OR: 1.11 [0.99-1.25], P = 0.074). CONCLUSION: LA minimum volume index best correlated with HFpEF in this patient cohort with diastolic dysfunction.

Electrocardiographic Criteria for the Diagnosis of Left Ventricular Hypertrophy.

BACKGROUND: Current electrocardiographic (ECG) criteria for the diagnosis of left ventricular hypertrophy (LVH) have low sensitivity. OBJECTIVES: The goal of this study was to test a new method to improve the diagnostic performance of the electrocardiogram. METHODS: The study was divided into 2 groups, a test and a validation cohort. In the test cohort, 94 patients were analyzed, including 47 with the diagnosis of hypertensive crisis and 47 with normal blood pressure at admission. Echocardiography was used to estimate the left ventricular mass index. Area under the curve (AUC) analysis was used for comparison of single and combined leads. The McNemar test was used to assess agreement among the ECG criteria against the left ventricular mass index. The proposed ECG criteria involved measuring the amplitude of the deepest S wave (SD) in any single lead and adding it to the S wave amplitude of lead V4 (SV4). Currently accepted LVH ECG criteria such as Cornell voltage and Sokolow-Lyon were used for comparison. The validation cohort consisted of 122 consecutive patients referred for an echocardiogram regardless of the admitting diagnosis. RESULTS: The SD was the most accurate single lead measurement for the diagnosis of LVH (AUC: 0.80; p < 0.001). When both cohorts were analyzed, the SD + SV4 criteria outperformed Cornell voltage with a significantly higher sensitivity (62% [95% confidence interval [CI]: 50% to 72%] vs. 35% [95% CI: 24% to 46%]). The specificities of all the criteria were ≥90%, with no significant difference among them. CONCLUSIONS: The proposed criteria for the ECG diagnosis of LVH improved the sensitivity and overall accuracy of the test.

Simplified prediction of postoperative cardiac surgery outcomes with a novel score: R2CHADS2.

OBJECTIVE: To compare the accuracy of R2CHADS2, CHADS2, and CHA2DS2-VASc scores vs the Society of Thoracic Surgeons (STS) score as predictors of morbidity and mortality after cardiovascular surgery. METHODS: All patients who underwent cardiothoracic surgery at our institution from January 2008 to July 2013 were analyzed. Only those patients who fulfilled the criteria for STS score calculation were included. The R2CHADS2 score was computed as follows: 2 points for GFR < 60 mL/min/1.73 m(2) (R2), prior stroke or TIA (S2); 1 point for history of congestive heart failure (C), hypertension (H), age ≥75 years (A), or diabetes (D). Area under the curve (AUC) analysis was used to estimate the accuracy of the different scores. The end point variables included operative mortality, permanent stroke, and renal failure as defined by the STS database system. RESULTS: Of the 3,492 patients screened, 2,263 met the inclusion criteria. These included 1,160 (51%) isolated valve surgery, 859 (38%) coronary artery bypass graft surgery, and 245 (11%) combined procedures. There were 147 postoperative events: 75 (3%) patients had postoperative renal failure, 48 (2%) had operative mortality, and 24 (1%) had permanent stroke. AUC analysis revealed that STS, R2CHADS2, CHADS2, and CHA2DS2-VASc reliably estimated all postoperative outcomes. STS and R2CHADS2 scores had the best accuracy overall, with no significant difference in AUC values between them. CONCLUSION: The R2CHADS2 score estimates postoperative events with acceptable accuracy and if further validated may be used as a simple preoperative risk tool calculator.

Edetate Disodium-Based Treatment for Secondary Prevention in Post-Myocardial Infarction Patients.

An abundance of data, known for decades, is available linking metals, such as lead and cadmium, with cardiovascular disease. However, the idea that these toxic metals could be a modifiable risk factor for atherosclerosis did not become apparent clinically until the completion of the Trial to Assess Chelation Therapy in 2012. This pivotal study was the first double-blind, randomized, controlled trial of its kind to demonstrate a clear improvement in cardiovascular outcomes with edetate disodium therapy in a secondary prevention, post-myocardial infarction population. This effect size was most striking in diabetic patients, where the efficacy of edetate disodium was comparable, if not superior, to that of current guideline-based therapies. Given the economic burden of diabetes and cardiovascular disease, the potential impact of this therapy could be enormous if the results of this study are replicated.

An example of the deleterious effects of right ventricular apical pacing.

Pacemaker implantation remains the mainstay of treatment in patients with symptomatic sinus node disease or severe heart block. Despite the dramatic benefits of this therapy, a high burden of ventricular pacing is known to have its disadvantages. Reported is the case of an 85-year-old woman with a history of sick sinus syndrome who presented with congestive heart failure after her atrioventricular sequential pacemaker defaulted to ventricular pacing mode as a result of battery depletion. After replacement of her generator and reinstitution of atrial pacing, dramatic improvements in her symptoms and echocardiographic findings were observed. Although it is difficult to predict which patients will ultimately develop cardiac decompensation as a result of ventricular pacing, closer follow-up and early recognition of these complications is essential to prevent adverse outcomes.

Usefulness of the CHA2DS2VASc score to predict postoperative stroke in patients having cardiac surgery independent of atrial fibrillation.

Despite its association with cardioembolic stroke, atrial fibrillation (AF) appears to be inconsistent as a risk factor for postoperative strokes in patients who underwent cardiac surgery. Furthermore, the relation between AF and the CHA2DS2VASc score has not been definitively established with respect to postoperative stroke. We retrospectively analyzed the records of all cardiac surgery performed at our institution between January 2008 and July 2013. Baseline characteristics, operative data, and postoperative outcomes were compared in patients who developed stroke with those who did not. Previously recognized stroke risk factors, including AF, were analyzed along with the CHADS2 and CHA2DS2VASc scores. A total of 3,492 consecutive patients were identified, of which 2,077 (60%) underwent valve surgery, 915 (26%) had coronary artery bypass grafting, 399 (11%) underwent combined coronary artery bypass grafting and valve procedures, and 101 (3%) had other cardiac operations. Postoperative ischemic strokes occurred in 44 patients (1.2%). The development of a stroke was associated with older age (74 ± 12 vs 69 ± 12, p = 0.008), preoperative antiplatelet medication use (38.6% vs 24.5%, p = 0.043), congestive heart failure (37% vs 20%, p = 0.002), and greater CHADS2 (2.48 ± 1.3 vs 1.98 ± 1.1, p = 0.015) and CHA2DS2VASc scores (4.2 ± 1.8 vs 3.4 ± 1.6, p = 0.002). Multivariable analysis demonstrated that the CHA2DS2VASc score was the only independent predictor of postoperative strokes (odds ratio 1.25; 95% confidence interval 1.05 to 1.5, p = 0.014). In conclusion, the CHA2DS2VASc score appears to predict postoperative strokes independent of the presence of AF.

Pleiotropic effects of the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors in pulmonary diseases: a comprehensive review.

The 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors (statins) are used extensively in the treatment of hyperlipidemia. They have also demonstrated a secondary benefit in a variety of other disease processes, actions which are known as pleiotropic effects. Review of the current pulmonary literature suggests a potential advantage of statin usage in a variety of pulmonary conditions. Our paper serves as a focused discussion on the pleiotropic effects of statins in the most common pulmonary disorders.

The use of nitrates in the prevention of contrast-induced nephropathy in patients hospitalized after undergoing percutaneous coronary intervention.

Contrast-induced nephropathy (CIN) is a significant cause of morbidity and mortality and effective strategies for its prevention are greatly needed. The purpose of this retrospective, single-center study was to investigate whether nitrate use during percutaneous coronary artery intervention reduces the incidence of CIN. Chart review of all individuals who underwent percutaneous coronary intervention (PCI) from April 2010 to March 2011 was done. Included in the study were patients who were admitted to the hospital after percutaneous coronary artery intervention and had baseline and follow-up creatinine measured. Patients with end-stage renal disease requiring dialysis and those patients with insufficient information to calculate Mehran score were excluded. There were 199 patients who met the eligibility criteria for inclusion in this study. In the identified population, postprocedure renal function was compared between 112 patients who received nitrates prior to coronary intervention and 87 who did not. Baseline characteristics were similar between the 2 groups. Contrast-induced nephropathy was defined as either a 25% or a 0.5 mg/dL, or greater, increase in serum creatinine during the first 48 to 72 hours after contrast exposure. Overall, 43 (21.6%) patients developed CIN post-PCI. Of the patients who received nitrates, 15.2% developed renal impairment when compared to 29.9% in those who did not (odds ratio [OR] = 0.42, 95% confidence interval [CI] 0.21-0.84, P = .014). Multivariate logistic regression analysis demonstrated that nitrate use was independently correlated with a reduction in the development of contrast nephropathy (OR = 0.334, 95% CI 0.157-0.709, P = .004). Additionally, of the various methods of nitrate administration, intravenous infusion was shown to be the most efficacious route in preventing renal impairment (OR = 0.42, 95% CI 0.20-0.90, P = .03). In conclusion, the use of nitrates prior to PCI, particularly intravenous nitroglycerin infusion, may be associated with a decreased incidence of CIN.