Association between right ventricular global longitudinal strain and mortality in intermediate-risk pulmonary embolism.

BACKGROUND: Right ventricular (RV) systolic dysfunction has been identified as a prognostic marker for adverse clinical events in patients presenting with acute pulmonary embolism (PE). However, challenges exist in identifying RV dysfunction using conventional echocardiography techniques. Strain echocardiography is an evolving imaging modality which measures myocardial deformation and can be used as an objective index of RV systolic function. This study evaluated RV Global Longitudinal Strain (RVGLS) in patients with intermediate risk PE as a parameter of RV dysfunction, and compared to traditional echocardiographic and CT parameters evaluating short-term mortality. METHODS: Retrospective single center cohort study of 251 patients with intermediate-risk PE between 2010 and 2018. The primary outcome was all-cause mortality at 30 days. Statistical analysis evaluated each parameter comparing survivors versus non-survivors at 30 days. Receiver operating characteristic (ROC) curves and Kaplan-Meier curves were used for comparison of the two cohorts. RESULTS: Altogether 251 patients were evaluated. Overall mortality rate was 12.4%. Utilizing an ROC curve, an absolute cutoff value of 17.7 for RVGLS demonstrated a sensitivity of 93% and specificity of 70% for observed 30-day mortality. Individuals with an RVGLS ≤17.7 had a 25 times higher mortality rate than those with RVGLS above 17.7 (HR 25.24, 95% CI = 6.0-106.4, p < .001). Area under the curve was (.855), RVGLS outperformed traditional echocardiographic parameters, CT findings, and cardiac biomarkers on univariable and multivariable analysis. CONCLUSIONS: Reduced RVGLS values on initial echocardiographic assessment of patients with intermediate-risk PE identified patients at higher risk for mortality at 30 days.

Re-Analyses of 8 Historical Trials in Cardiovascular Medicine Assessing Multimorbidity Burden and Its Association with Treatment Response.

OBJECTIVE: The purpose of this study was to examine the multimorbidity burden of clinical trial participants and assess its association with treatment response. METHODS: We conducted a reanalysis of patient level data. There were 29,954 participants from 8 clinical trials containing 11 comparisons between an intervention and control condition. Patients were classified by Charlson Comorbidity Index (CCI) score. The primary outcomes were the primary study endpoints as originally specified for each trial. A Cox model that included the CCI score groups, the randomized group, and their interaction, was used to compare the primary outcome between randomized groups. The interaction term between randomized group and comorbidity index allowed the treatment effect to differ by level of comorbidity index and comprised the primary effect of interest. Hazard ratios and risk differences were reported for all comparisons. RESULTS: The mean CCI scores of trial populations ranged from 2.1 to 3.9 points, and the percentage of patients with scores ≥5 from 3% to 39%. Tests of interaction terms in models yielded P values ≤ .10 for 4/11 comparisons and ≤ .05 for 2/11 comparisons. In 3 additional comparisons, potentially important treatment variation on an absolute scale was observed despite interaction tests with P values > .10 on the relative scale. CONCLUSIONS: These trials were mainly composed of patient populations with CCI scores ≤4. Despite this, biologically plausible treatment interactions were commonly suggested. These results are hypothesis generating; confirmation of results would require larger studies or studies targeted specifically toward patients with higher levels of multimorbidity.

Some patients with type 2 diabetes may benefit from intensive glycaemic and blood pressure control: A post-hoc machine learning analysis of ACCORD trial data.

AIM: The action to control cardiovascular risk in diabetes (ACCORD) trial showed a neutral average treatment effect of intensive blood glucose and blood pressure (BP) controls in preventing major adverse cardiovascular events (MACE) in individuals with type 2 diabetes. Yet, treatment effects across patient subgroups have not been well understood. We aimed to identify patient subgroups that might benefit from intensive glucose or BP controls for preventing MACE. MATERIALS AND METHODS: As a post-hoc analysis of the ACCORD trial, we included 10 251 individuals with type 2 diabetes. We applied causal forest and causal tree models to identify participant characteristics that modify the efficacy of intensive glucose or BP controls from 68 candidate variables (demographics, comorbidities, medications and biomarkers) at the baseline. The exposure was (a) intensive versus standard glucose control [glycated haemoglobin (HbA1c) <6.0% vs. 7.0%-7.9%], and (b) intensive versus standard BP control (systolic BP <120 vs. <140 mmHg). The primary outcome was MACE. RESULTS: Compared with standard glucose control, intensive one reduced MACE in those with baseline HbA1c <8.5% [relative risk (RR): 0.79, 95% confidence interval (CI): 0.67-0.93] and those with estimated glomerular filtration rate ≥106 ml/min/1.73 m2 (RR: 0.74, 95% CI: 0.55-0.99). Intensive BP control reduced MACE in those with normal high-density lipoprotein levels (women >55 mg/dl, men >45 mg/dl; RR: 0.51, 95% CI: 0.34-0.74). Risk reductions were not significant in other patient subgroups. CONCLUSIONS: Our findings suggest heterogeneous treatment effects of intensive glucose and BP control and could provide biomarkers for future clinical trials to identify more precise HbA1c and BP treatment goals for individualized medicine.

The Impact of Polypill on Adherence and Cardiovascular Outcomes: A Comprehensive Systematic Review with Meta-Analysis.

BACKGROUND: Cardiovascular disease (CVD) remains a leading cause of morbidity and mortality worldwide. Polypills, containing various combinations of medications for primary and secondary CVD prevention, have been developed to enhance medication adherence and reduce the healthcare burden of CVD. However, their effectiveness compared to usual care remains uncertain. OBJECTIVE: This meta-analysis aimed to evaluate the effects of polypills on cardiovascular risk factors, major adverse cardiovascular events (MACE), and medication adherence. METHODS: We conducted a comprehensive search for large-scale randomized controlled trials and observational studies comparing the effects of polypills versus usual care on CVD risk factors and events. Outcomes included changes in systolic and diastolic blood pressure (SBP, DBP), lipid profiles, occurrence of MACE, and medication adherence. RESULTS: The use of polypills led to a statistically significant yet clinically modest reduction in SBP (mean difference -1.47 mmHg, 95% CI: -2.50 to -0.44, p<0.01) and DBP (mean difference- 1.10 mmHg, 95% CI: -1.68 to -0.51, p< 0.01) compared to usual care. Polypills also showed a significant reduction in the risk of MACE (RR: 0.86, 95% CI: 0.77 -0.95, p<0.01). There was a non-significant reduction in LDL and HDL levels. Adherence to medication improved by up to 17% in polypill users compared to those on usual care (p < 0.01). A multivariable metaregression analysis suggested that adherence may be the underlying factor responsible for the observed effect of the polypills on blood pressure. CONCLUSION: Polypills were found to significantly reduce SBP, DBP and MACE. An improvement in medication adherence was also observed among polypill users, which might be responsible for the significant reduction in SBP observed users. Future research might benefit from exploring a more personalized approach to the composition of polypills, which could reveal a more clinically significant impact of increased adherence on CVD outcomes.

Acute Myocardial Infarction Revealed by an Escape Rhythm in a Patient With Failed Sgarbossa Criteria.

This case report describes a man in his 80s with a medical history of essential hypertension who presented to the emergency department with sudden onset epigastric pain.

Clinical presentation and neurovascular manifestations of cardiac myxomas and papillary fibroelastomas: a retrospective single-institution cohort study.

Background: Primary cardiac tumors are often benign and commonly present as cardiac myxomas (CMs) or papillary fibroelastomas (CPFEs). There is a paucity of prognostic indicators for tumor burden or potential for embolic cerebrovascular events (CVEs). This study was performed to address these gaps. Methods: Medical records at the University of Florida Health Shands Hospital between 1996 and 2021 were screened to identify patients with CMs or CPFEs. Clinical features, echocardiographic reports, and CVE outcomes were quantitatively assessed. Results: A total of 55 patients were included in the study: 28 CM (50.9%) and 27 CPFE (49.1%) patients. Baseline patient characteristics were similar among patients. The neutrophil-lymphocyte ratio was correlated (p < 0.005 in all cases) to three metrics of tumor size in both CM (r = 64-67%) and CPFE (r = 56-59%). CVEs were the presenting symptom in 30 (54.5%) patients. CVE recurrence was high; the 5-year CVE recurrence rate in patients with tumor resection was 24.0% compared to 60.0% without resection. No baseline patient characteristics or tumor features were associated with an initial presentation of CVEs compared to any other indication. Univariate analysis indicated that prolonged duration to surgical resection, left atrial enlargement, male sex, and a neutrophil-lymphocyte ratio >3.0 at the follow-up were significantly associated with 5-year CVE recurrence. Left atrial enlargement and a neutrophil-lymphocyte ratio >3.0 at the follow-up remained significantly associated with 5-year CVE recurrence in multivariate analysis. Conclusion: The neutrophil-lymphocyte ratio may prognosticate tumor size and recurrence of neurologic events. An increased risk of CVE within 5 years of mass resection is almost exclusive to patients initially presenting with CVEs.

Longitudinal cardiac remodeling in collegiate American football players as assessed by echocardiography during their collegiate career.

BACKGROUND: Studies on the longitudinal effects of intense physical training on cardiac remodeling are limited, especially in American collegiate football players. HYPOTHESIS: College-level American football training will result in remodeling in a pattern consistent of a sport with moderate static and dynamic demands with increases in both wall and chamber sizes. METHODS: We studied 85 American collegiate football players who underwent transthoracic echocardiogram (TTE) for asymptomatic or mild COVID-19-related illness and compared the changes in echo dimensions to their preparticipation screening TTE. Pre- and posttraining variables were compared using a paired t-test for normally distributed variables. RESULTS: Mean age was 19 years ± 1 and 61% of athletes were Black. Mean follow-up between TTEs was 21 ± 13 months. There was an increase in left atrial volume index (26.4 ± 5.5 to 32.8 ± 8.4 mL/m2 , p < .001), LV end diastolic diameter (5.13 ± 0.4 to 5.27 ± 0.4 cm, p = .003), basal RV diameter (3.28 ± 0.7 to 3.83 ± 0.5 cm, p = <.001), LV mass index (86.7 ± 15.3 to 90.1 ± 15.3, p = .015), and aortic root diameter (3.1 ± 0.4 to 3.2 ± 0.3 cm, p = .03) from pre- to posttraining, with a slightly greater magnitude in athletes with >2 years of training. Presence of left atrial enlargement (≥35 mL/m2 ) increased from 2.9% to 29% pre- to postparticipation in athletes with >2 years training. No significant changes in wall thickness, diastolic function, or right ventricular systolic function were observed. CONCLUSION: American football players college-level training was associated with increases in left and right ventricular chamber sizes, left atrial size, and aortic root diameter.

Impact of Baseline Heart Failure on Acute Pulmonary Embolism Risk Stratification and Clinical Outcomes.

Among patients with acute pulmonary embolism (PE), abnormal cardiac biomarkers and elevated right ventricular to left ventricular (RV/LV) diameter ratio are associated with increased morbidity and mortality. However, subjects with baseline heart failure (HF) have abnormalities in cardiac chamber dimensions and biomarkers. We sought to describe risk stratification variables in a cohort with acute PE and categorized HF status as no HF, HF with reduced ejection fraction (HFrEF), or HF with preserved ejection fraction (HFpEF). In total, 182 subjects were identified for this study, of whom 142 were categorized as having no HF, 16 as having HFrEF, and 24 as having HFpEF. The median age was 65 years [interquartile range 51 to 75 years], and 43% were male. Subjects with HFrEF had significantly greater LV diameters and significantly lower RV/LV diameter ratio (no HF 0.94, HFrEF 0.65, HFpEF 0.89, p = 0.002). Subjects with HFrEF also had significantly higher B-type natriuretic peptide levels (no HF 112 pg/mL, HFrEF 835 pg/mL, HFpEF 241 pg/mL, p <0.001) and higher 90-day mortality rates. Among subjects with acute PE, those with baseline HFrEF had significantly greater LV diameter and lower RV/LV diameter ratio than those of patients with HFpEF or no HF. In addition, subjects with HFrEF had significantly higher B-type natriuretic peptide levels and worse survival at 90 days. In conclusion, these results indicate that PE risk stratification using current guidelines, especially reliance on RV/LV ratio, is inaccurate among subjects with baseline HFrEF.

Beta-blocker use in patients with chronic obstructive pulmonary disease: A systematic review: A systematic review of ßB in COPD.

Beta-blockers (ßB) are a frequently used class of medications. Although ßB have many indications, those related to cardiovascular disease are among the most common and important. However, in patients with chronic obstructive pulmonary disease (COPD), ßB are used less often due to concerns about an unfavorable impact on respiratory morbidity and mortality. We performed a systematic review to assess the safety of ßB in patients with COPD. We included a total of 2 randomized controlled trials and 28 observational studies. The majority found statistically significant reductions in mortality. The two higher quality observational studies reported increased mortality with ßB. The risk of COPD exacerbations was reduced in about half of the studies. Nonetheless, there were significant biases that confounded the results. The highest quality RCT found a significant increase in severe and very severe COPD exacerbations with ßB use. In conclusion, data on the safety of ßB in patients with COPD are conflicting. However, given higher quality evidence showed harm with their use, ßB should be prescribed with caution in patients with COPD, including patients with cardiac indication for ßB.

Association between statin exposure and diabetes incidence among privately-insured patients before and after applying a novel technique to control for selection bias.

INTRODUCTION: The association between statins and incident diabetes mellitus (DM) in observational studies is much larger than that reported from randomized controlled trials. We sought to assess this association using a novel design controlling for selection bias. METHODS: Using data from MarketScan, we identified a cohort of non-diabetic patients who initiated a statin and matched them to patients not taking statins. From the statin-user cohort, we identified two subgroups: patients who received statin refills for >6 months (continuers) and patients who received statin refills <6 months (discontinuers). Patients were followed for a minimum of two years to determine incident DM. RESULTS: We included 442,526 patients, divided equally between statin users and non-users. Statin use was associated with increased DM (9.9% vs. 4.4%, HR 2.2, p < 0.001). Among the 221,263 statin users, there were 194,357 continuers and 26,906 discontinuers. There was no significant difference in the incidence rate of DM between both groups (10.0% vs. 9.3%, HR 1.03, p = 0.22). CONCLUSIONS: Statin use was strongly associated with incident diabetes when users were compared to non-users but not when continuers were compared to discontinuers. Selection bias confounds the association between statin use and incident diabetes in observational studies.

The Slower, the Better: Wide Complex Tachycardia Triggered by Flecainide in an Elderly Female.

Class IC antiarrhythmics are generally considered a safe means of treating many common arrhythmias such as atrial fibrillation (a-fib), atrial flutter (a-flutter), and paroxysmal supraventricular tachycardia (PSVT). Essentially, flecainide works by binding and blocking sodium channels more effectively at higher heart rates. However, this class of drugs is known to exhibit use dependence which could predispose patients to the development of malignant arrhythmias during episodes of tachycardia. In this case, we present a patient who was being treated with flecainide for a-fib who ultimately developed a wide complex tachycardia after her metoprolol was held.

Resource Utilization Following Coronary Computed Tomographic Angiography and Stress Echocardiography in Patients Presenting to the Emergency Department With Chest Pain.

This study aimed to assess long-term resource utilization and outcomes in patients with acute chest pain who underwent coronary computed tomography angiography (CCTA) and stress echocardiography (SE). This was a retrospective, propensity-matched analysis of health insurance claims data for a national sample of privately insured patients over the period January 1, 2011, to December 31, 2014. There were 3,816 patients matched 1:1 who received either CCTA (n = 1,908) or SE (n = 1,908). Patients were seen in the emergency department (ED) between January 1, 2011, and December 31, 2011 with a primary diagnosis of chest pain and received either CCTA or SE within 72 hours as the first noninvasive test and maintained continuous enrollment in the database from the time of the ED encounter through December 31, 2014. All individual patient data were censored at 3 years. Compared with SE, CCTA was associated with higher odds of downstream cardiac catheterization (9.9% vs 7.7%, adjusted odds ratio [AOR] 1.28, 95% confidence interval (CI) 1.00 to 1.63), future noninvasive testing (27.7% vs 22.3%, AOR 1.22, 95% CI 1.05 to 1.42), and return ED visits or hospitalization for chest pain at 3 years (33.1% vs 24.2%, AOR 1.37, 95% CI 1.19 to 1.59). There were no statistically significant differences in new statin use (15.5% vs 14.9%, AOR 1.04, 95% CI 0.85 to 1.28), coronary revascularization (2.7% vs 2.2%, AOR 1.25, 95% CI 0.77 to 2.01) or hospitalization for acute myocardial infarction (0.9% vs 0.9%, AOR 0.96, 95% CI 0.47 to 1.99). In conclusion, in patients who present to the ED with chest pain, CCTA is associated with increased downstream resource utilization compared with SE with no differences in long-term cardiovascular outcomes.

Direct Oral Anticoagulants in Patients with Atrial Fibrillation and Bioprosthetic Valves-A Systematic Review and Meta-analysis.

Oral anticoagulation is recommended for patients with atrial fibrillation and an elevated stroke risk. Direct oral anticoagulants (DOACs) are generally preferred over vitamin K antagonists. Nonetheless, there controversy persists regarding whether DOACs should be used in patients with atrial fibrillation and bioprosthetic valves. Therefore, we conducted this systematic review and meta-analysis to assess the safety and efficacy of DOACs compared to warfarin in this patient population. We performed a systematic search of the MEDLINE and PubMed Central databases for relevant articles. The incidence rate and risk ratio (RR) of all-cause mortality, cardiovascular mortality, ischemic stroke/systemic thromboembolism, hemorrhagic stroke/intracranial bleeding, major bleeding, and minor bleeding were calculated. A total of eight studies were included, including 5,300 patients (stratified as 1,638 patients in the DOAC arm and 3,662 patients in the warfarin arm). There was no significant difference in the rate of stroke/systemic thromboembolism [RR: 0.85; 95% confidence interval (CI): 0.43-1.69], all-cause mortality (RR: 0.77; 95% CI: 0.53-1.11), or cardiovascular death (RR: 0.81; 95% CI: 0.40-1.63) between DOACs and warfarin. Major bleeding and hemorrhagic stroke/intracranial bleeding were similar between both treatment arms (RR: 0.61; 95% CI: 0.35-1.06 and RR: 0.27; 95% CI: 0.06-1.13, respectively). In conclusion, DOACs are safe and effective in patients with atrial fibrillation and bioprosthetic valves. Future large-scale randomized studies are warranted to confirm this observation.

Association Between Baseline Diastolic Blood Pressure and the Efficacy of Intensive vs Standard Blood Pressure-Lowering Therapy.

Importance: Low diastolic blood pressure (DBP) has been found to be associated with increased adverse cardiovascular events; however, it is unknown whether intensifying blood pressure therapy in patients with an already low DBP to achieve a lower systolic blood pressure (SBP) target is safe or effective. Objective: To evaluate whether there is an association of baseline DBP and intensification of blood pressure-lowering therapy with the outcomes of all-cause death and cardiovascular events. Design, Setting, and Participants: This cohort study analyzed patients who were randomized to intensive or standard BP control in the Action to Control Cardiovascular Risk in Diabetes-Blood Pressure (ACCORD-BP) trial and Systolic Blood Pressure Intervention Trial (SPRINT). Data were collected from September 1999 to June 2009 (ACCORD-BP) and from October 2010 to August 2015 (SPRINT). Data were analyzed from December 2020 to June 2021. Exposures: Baseline DBP as a continuous variable. Main Outcomes and Measures: All-cause death and a composite cardiovascular end point (CVE) that included cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke. Results: A total of 14 094 patients (mean [SD] age, 66.2 [8.9] years; 8504 [60.4%] men) were included in this analysis. There were significant nonlinear associations between baseline DBP and all-cause death (eg, baseline DBP 50 vs 80 mm Hg: hazard ratio [HR], 1.48; 95% CI, 1.06-2.08; P = .02) and the composite CVE (eg, baseline DBP 50 vs 80 mm Hg: HR, 1.45; 95% CI, 1.27-3.04; P = .003) observed among all participants. Findings for the interaction between baseline DBP and treatment group assignment for all cause death did not reach statistical significance. For intensive vs standard therapy, the HR of death for a baseline DBP of 50 mm Hg was 1.80 (95% CI, 0.95-3.39; P = .07) and that for a baseline DBP of 80 mm Hg was 0.77 (95% CI, 0.59-1.01; P = .05). Overall, there was no interaction found between baseline DBP and treatment group assignment for the composite CVE. Over the range of baseline DBP values, significant reductions in the composite CVE for patients assigned to intensive vs standard therapy were found for baseline DBP values of 80 mm Hg (HR, 0.78; 95% CI, 0.62-0.98; P = .03) and 90 mm Hg (HR, 0.74; 95% CI, 0.55-0.98; P = .04). Conclusions and Relevance: This pooled cohort study found no evidence of a significant interaction between baseline DBP and treatment intensity for all-cause death or for a composite CVE. These results are hypothesis generating and merit further study.

Oral Anticoagulation Use in High-Risk Patients Is Improved by Elimination of False-Positive and Inactive Atrial Fibrillation Cases.

BACKGROUND: Multiple registries have reported that >40% of high-risk atrial fibrillation patients are not taking oral anticoagulants. The purpose of our study was to determine the presence or absence of active atrial fibrillation and CHA2DS2-VASc (Congestive heart failure, Hypertension, Age ≥75 y, Diabetes mellitus, prior Stroke [or transient ischemic attack or thromboembolism], Vascular disease, Age 65-74 y, Sex category) risk factors to accurately identify high-risk atrial fibrillation (CHA2DS2-VASc ≥2) patients requiring oral anticoagulants and the magnitude of the anticoagulant treatment gap. METHODS: We retrospectively adjudicated 6514 patients with atrial fibrillation documented by at least one of: billing diagnosis, electronic medical record encounter diagnosis, electronic medical record problem list, or electrocardiogram interpretation. RESULTS: After review, 4555/6514 (69.9%) had active atrial fibrillation, while 1201 had no documented history of atrial fibrillation and 758 had a history of atrial fibrillation that was no longer active. After removing the 1201 patients without a confirmed atrial fibrillation diagnosis, oral anticoagulant use in high-risk patients increased to 71.1% (P < .0001 compared with 62.9% at baseline). Oral anticoagulant use increased to 79.7% when the 758 inactive atrial fibrillation patients were also eliminated from the analysis (P < .0001 compared with baseline). In the active high-risk atrial fibrillation group, there was no significant difference in the use of oral anticoagulants between men (80.7%) and women (78.8%) with a CHA2DS2-VASc ≥2, or in women with a CHA2DS2-VASc ≥3 (79.9%). CONCLUSIONS: Current registries and health system health records with unadjudicated diagnoses over-report the number of high-risk atrial fibrillation patients not taking oral anticoagulants. Expert adjudication identifies a smaller treatment gap than previously described.