Differential effects of cigarette smoking on cardiovascular disease in females: A narrative review and call to action.

OBJECTIVE: Cigarette smoking continues to be a major driver in the incidence and progression of cardiovascular disease (CVD). As females become an increasingly larger fraction of those who smoke it is imperative that the sex-specific effects of smoking be further explored and acted upon. METHODS: This narrative review describes current evidence on the differential effects of smoking on CVD in females and the need to improve treatment. RESULTS: Evidence to date suggests that smoking has disproportionately negative effects on the cardiovascular (CV) system in females, especially in those who are younger. Usually, the onset of CVD is later in females than males, but smoking decreases or eliminates this gap. Females are also more likely to develop types of CVD closely tied to smoking, such as ST-elevated myocardial infarctions, with even higher rates among those who are younger. Possible mechanisms for these worse outcomes in females include a complex interplay between nicotine, other products of combusted cigarettes, and hormones. Sex differences also exist in treatment for smoking. In females, Varenicline appears more effective than either Bupropion or nicotine replacement therapy while in males, all three therapies show similar efficacy. Disparities in smoking are also apparent in secondary prevention settings. Females and males are entering secondary prevention with equal rates of smoking, with potentially higher levels of exposure to the byproducts of smoking in females. CONCLUSIONS: These disproportionately negative outcomes for females who smoke require additional research and these persisting rates of smoking suggest a need for female-specific approaches for treating smoking.

Updates on Non-Statin LDL-Lowering Therapy.

PURPOSE OF REVIEW: There is ample evidence of the benefits and safety of low-density lipoprotein (LDL)-lowering therapies in the prevention of atherosclerotic cardiovascular disease. While statins remain the first-line agent for LDL reduction, several new therapies are now available. This narrative review provides an overview of currently available non-statin LDL-lowering agents, specifically mechanisms of action and data on efficacy and safety. It also discusses recommendations on their use in clinical practice. RECENT FINDINGS: Ezetimibe, PCSK9 inhibitors, and bempedoic acid have proven safe and efficacious in reducing cardiovascular events in large randomized controlled trials. Inclisiran is a promising agent that suppresses PCSK9 mRNA translation and is currently under investigation in a large clinical outcomes randomized controlled trial assessing its effect on clinical outcomes. Expert consensus advocates for lower LDL targets in higher risk patients and escalation to or a combination of non-statin therapies as needed to achieve these goals.

Initial Evaluation and Management of Patients Presenting with Acute Chest Pain in the Emergency Department.

PURPOSE OF THE REVIEW: To review the initial evaluation of chest pain in the emergency department (ED), with a focus on coronary artery disease (CAD) and acute coronary syndromes (ACS), using consensus statements from major cardiovascular disease organizations. RECENT FINDINGS: Major cardiovascular organizations have released consensus statements on this topic, notably the 2021 AHA/ACC/ASE/CHEST/SAEM/SCCT/SCMR Guideline for the Evaluation and Diagnosis of Chest Pain and the 2022 ACC Expert Consensus Decision Pathway on the Evaluation and Disposition of Acute Chest Pain in the Emergency Department. Also, recent studies have evaluated the use of high sensitivity troponin (hs-cTn) to safely rule out myocardial infarction (MI), with the development of rule-out pathways designed to be utilized in the ED. This review highlights the comprehensive differential diagnoses of chest pain in the ED and urgent management of these etiologies, with a focus on cardiovascular etiologies. There exist a few rule-out pathways recommended by major cardiovascular organizations, notably the high-STEACS and the ESC 0/1 and 0/2 pathways that can safely and quickly discharge patients with low risk of MI.

Safety of routine protamine in the reversal of heparin in percutaneous coronary intervention: A systematic review and meta-analysis.

OBJECTIVES: To determine the safety and efficacy of protamine in the reversal of heparin in percutaneous coronary intervention (PCI). BACKGROUND: Heparin is routinely used for anticoagulation in PCI. Protamine is not used routinely to reverse heparin's effects in PCI, partly due to the perceived risk of stent thrombosis. METHODS: Relevant studies published in English were searched for in PubMed, Embase, and Cochrane databases from inception to April 26th, 2023. Our primary outcome of interest was stent thrombosis in patients receiving PCI for all indications. Secondary outcomes included mortality, major bleeding complications, and hospitalization length. Dichotomous outcomes were analyzed using a Mantel-Haenszel random-effects model and expressed as odds ratios (OR) with their 95% confidence intervals (CI), while continuous outcomes were analyzed using an inverse variance random-effects model expressed as mean differences (MD) with their 95% CI. RESULTS: 11 studies were included in our analysis. Protamine use was not associated with stent thrombosis: OR 0.58, 95% CI: 0.33, 1.01 (p = 0.05) nor with mortality (p = 0.89). Protamine administration was associated with a decreased incidence of major bleeding complications: OR 0.48; 95% CI: 0.25, 0.95 (p = 0.03) and decreased length of hospitalization (p < 0.0001). CONCLUSIONS: In patients pre-treated with dual antiplatelet therapy (DAPT), protamine may be a safe and efficacious option to facilitate earlier sheath removal, reduce major bleeding complications, and reduce length of hospitalization without increased risk of stent thrombosis.

Association of Cardiovascular Medications With Adverse Outcomes in a Matched Analysis of a National Cohort of Patients With COVID-19.

Background: The use of statins, angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin II receptor blockers (ARBs), and anticoagulants may be associated with fewer adverse outcomes in COVID-19 patients. Methods: Nested within a cohort of 800,913 patients diagnosed with COVID-19 between April 1, 2020 and June 24, 2021 from the Optum COVID-19 database, three case-control studies were conducted. Cases-defined as persons who: (1) were hospitalized within 30 days of COVID-19 diagnosis (n = 88,405); (2) were admitted to the intensive care unit (ICU)/received mechanical ventilation during COVID-19 hospitalization (n = 22,147); and (3) died during COVID-19 hospitalization (n = 2300)-were matched 1:1 using demographic/clinical factors with controls randomly selected from a pool of patients who did not experience the case definition/event. Medication use was based on prescription ≤90 days before COVID-19 diagnosis. Results: Statin use was associated with decreased risk of hospitalization (adjusted odds ratio [aOR], 0.72; 95% confidence interval [95% CI], 0.69, 0.75) and ICU admission/mechanical ventilation (aOR, 0.90; 95% CI, 0.84, 0.97). ACEI/ARB use was associated with decreased risk of hospitalization (aOR, 0.67; 95% CI, 0.65, 0.70), ICU admission/mechanical ventilation (aOR, 0.92; 95% CI, 0.86, 0.99), and death (aOR, 0.60; 95% CI, 0.47, 0.78). Anticoagulant use was associated with decreased risk of hospitalization (aOR, 0.94; 95% CI, 0.89, 0.99) and death (aOR, 0.56; 95% CI, 0.41, 0.77). Interaction effects-in the model predicting hospitalization-were statistically significant for statins and ACEI/ARBs (P < .0001), statins and anticoagulants (P = .003), ACEI/ARBs and anticoagulants (P < .0001). An interaction effect-in the model predicting ventilator use/ICU-was statistically significant for statins and ACEI/ARBs (P = .002). Conclusions: Statins, ACEI/ARBs, and anticoagulants were associated with decreased risks of the adverse outcomes under study. These findings may provide clinically relevant information regarding potential treatment for patients with COVID-19.

Acute chest pain in a patient with left bundle branch pacing.

We present a patient with left bundle branch (LBB) electronic ventricular pacing with chest pain. ECG showed ventricular pacing and ST elevation in the inferolateral leads. At first it was felt that the Sgarbossa criteria for STEMI in electronic ventricular pacing are not met. However, as symptoms persisted, emergency coronary angiography was performed showing complete occlusion of the left circumflex artery. As LBB pacing results in narrow QRS complexes with incomplete right bundle branch block, ST-segment deviation should not be ignored and the Sgarbossa criteria for patients with LBB block or right ventricular electronic pacing should not be applied.

Etiologies of In-hospital cardiac arrest: A systematic review and meta-analysis.

BACKGROUND: Etiologies of in-hospital cardiac arrest (IHCA) in general wards may differ from etiologies of out-of-hospital cardiac arrest (OHCA) given the different clinical characteristics of these patient populations. An appreciation for the causes of IHCA may allow the clinician to appropriately target root causes of arrest. METHODS: MEDLINE/PubMed, EMBASE, and Google Scholar were queried from inception until May 31, 2021. Studies reporting etiologies of IHCA were included. A random effects meta-analysis of extracted data was performed using Review Manager 5.4. RESULTS: Of 12,451 citations retrieved from the initial literature search, 9 were included in the meta-analysis. The most frequent etiologies of cardiac arrest were hypoxia (26.46%, 95% confidence interval [CI] 14.19-38.74%), acute coronary syndrome (ACS) (18.23%, 95% CI 13.91-22.55%), arrhythmias (14.95%, 95% CI 0-34.93%), hypovolemia (14.81%, 95% CI 6.98-22.65%), infection (14.36%, 95% CI 9.46-19.25%), and heart failure (12.64%, 95% CI 6.47-18.80%). Cardiac tamponade, electrolyte disturbances, pulmonary embolism, neurological causes, toxins, and pneumothorax were less frequent causes of IHCA. Initial rhythm was unshockable (pulseless electrical activity or asystole) in 69.83% of cases and shockable (ventricular tachycardia or ventricular fibrillation) in 21.75%. CONCLUSION: The most prevalent causes of IHCA among the general wards population are hypoxia, ACS, hypovolemia, arrythmias, infection, heart failure, three of which (arrhythmia, infection, heart failure) are not part of the traditional "H's and T's" of cardiac arrest. Other causes noted in the "H's and T's" of advanced cardiac life support do not appear to be important causes of IHCA.

Managing Thrombosis and Hemorrhage in a Man with Myocardial Infarction and Traumatic Hemopericardium with Cardiac Tamponade.

A 79-year-old man had an out-of-hospital acute ST-segment-elevation myocardial infarction with cardiac arrest. Cardiopulmonary resuscitation performed by a bystander resulted in traumatic hemopericardium. We discuss the patient's case, highlight the challenges of managing simultaneously life-threatening thrombosis and hemorrhage, and present our conclusions regarding the patient's eventual death.

Intravenous magnesium in the management of rapid atrial fibrillation: A systematic review and meta-analysis.

BACKGROUND: The aim of this meta-analysis is to investigate the effectiveness of intravenous magnesium (IV Mg2+) in rate and rhythm control of rapid atrial fibrillation (AF) when administered in addition to standard-of-care for non-post-operative patients. Previous meta-analyses on this topic have demonstrated the efficacy of IV Mg2+ in achieving rate control, but not rhythm control. METHODS: Six randomized controlled trials comparing IV Mg2+ to placebo in the treatment of rapid AF were obtained from electronic databases totaling 745 patients. Outcomes were analyzed using a Mantel-Haenszel random-effects model and expressed as odds ratios (OR) for dichotomous outcomes with their 95% confidence intervals (CIs). RESULTS: Our pooled analysis showed that IV Mg2+ given in addition to standard-of-care was superior in achieving rate control (63% vs 40%; OR 2.49, 95% CI 1.80-3.45) and rhythm conversion to sinus (21% vs. 14%, OR 1.75, 95% CI 1.08-2.84) compared to standard-of-care alone. Flushing was more frequently observed in patients receiving IV Mg2+ compared to placebo (9% vs. 0.4%, OR 19.79, 95% CI 4.30-91.21). Subgroup analysis showed the superiority of a lower dose of IV Mg2+, which we designated as 5 g or lower (24% vs 13%, OR 2.10, 95% CI 1.22-3.61) compared to the higher dose (>5 g) (16% vs 13%, OR 1.23, 95% CI 0.65-2.32) in rhythm control when compared to placebo. CONCLUSIONS: IV Mg2+ administered in conjunction with standard-of-care is effective for rate control and modestly effective for restoration of sinus rhythm in rapid AF without clinically significant adverse effects.

Pathophysiology, Diagnosis, and Management of the No-Reflow Phenomenon.

Successful reperfusion of an infarct-related coronary artery by primary percutaneous intervention or fibrinolysis during acute ST-elevation myocardial infarction (STEMI) does not always restore myocardial tissue perfusion, a phenomenon termed "no-reflow." Herein we discuss the pathophysiology of this highly prevalent phenomenon and highlight the most salient aspects of its clinical diagnosis and management as well as the limitations of presently used methods. There is a great need for understanding the dynamic nature of no-reflow, as its occurrence is associated with poor cardiovascular outcomes. The no-reflow phenomenon may lend an explanation to the lack of further improvements in in-hospital mortality in STEMI patients despite decreases in door-to-balloon time. Hence, no-reflow potentially presents an important target for investigators interested in improving outcomes in STEMI.

The Role of Non-coding RNAs in Ischemic Myocardial Reperfusion Injury.

MicroRNAs (miRNA) are non-coding RNAs that regulate gene expression in up to 90% of the human genome through interactions with messenger RNA (mRNA). The expression of miRNAs varies and changes in diseased and healthy states, including all stages of myocardial ischemia-reperfusion and subsequent ischemia-reperfusion injury (IRI). These changes in expression make miRNAs an attractive potential therapeutic target. Herein, we review the differences in miRNA expression prior to ischemia (including remote ischemic conditioning and ischemic pre-conditioning), the changes during ischemia-reperfusion, and the changes in miRNA expression after IRI, with an emphasis on inflammatory and fibrotic pathways. Additionally, we review the effects of manipulating the levels of certain miRNAs on changes in infarct size, inflammation, remodeling, angiogenesis, and cardiac function after either ischemia-reperfusion or permanent coronary ligation. Levels of target miRNA can be increased using molecular mimics ("agomirs"), or can be decreased by using "antagomirs" which are antisense molecules that act to bind and thus inactivate the target miRNA sequence. Other non-coding RNAs, including long non-coding RNAs and circular RNAs, also regulate gene expression and have a role in the regulation of IRI pathways. We review the mechanisms and downstream effects of the miRNAs that have been studied as therapy in both permanent coronary ligation and ischemia-reperfusion models.

Outcomes of Robotically Assisted Versus Manual Percutaneous Coronary Intervention: A Systematic Review and Meta-Analysis.

OBJECTIVE: We performed a systematic review and meta-analysis of existing studies from the literature comparing robotically assisted (RA) percutaneous coronary intervention (PCI) to manual PCI (M-PCI). BACKGROUND: RA-PCI is a novel technology that allows the operator to perform PCI from a shielded cockpit using a remote-control module. METHODS: MEDLINE/PubMed, EMBASE, and Google Scholar were queried from inception until May 31, 2018 for relevant studies comparing clinical outcomes between RA-PCI and M-PCI. The random-effects model was utilized to compute the summary effect size. RESULTS: Of 2050 retrieved citations, five studies were included, with a total of 148 patients in the RA-PCI arms and 493 patients in the M-PCI control arms. Lower operator radiation exposure was observed with RA-PCI compared with M-PCI. There were no statistically significant differences in total stents per case, PCI time, fluoroscopy time, or procedural success rates between the two groups. CONCLUSIONS: In carefully selected patients, RA-PCI was associated with reduced operator radiation exposure compared with M-PCI, but there were no significant differences in procedural success rate, patient radiation exposure, contrast dose, or procedure time.

Do We Need Potent Intravenous Antiplatelet Inhibition at the Time of Reperfusion During ST-Segment Elevation Myocardial Infarction?

Acute myocardial infarction (MI) is still a large source of morbidity and mortality worldwide. Although early reperfusion therapy has been prioritized in the modern era of percutaneous coronary intervention and thrombolysis, attempts at incremental improvements in clinical outcomes by reducing MI size have not been successful so far. Herein, we review the studies that have evaluated immediate-onset antiplatelet therapy as attempts to improve meaningful clinical outcomes in ST-segment elevation MI (STEMI). Unfortunately, many of the adjunctive pharmacotherapies have proven to be disappointing. Recent studies performed in the background of routine oral administration of P2Y12 adenosine receptor inhibitors, which may take several hours to take full effect, and aspirin have largely shown no improvement in outcomes, despite an earlier onset of antiplatelet activity of the investigative agents. Further progress in improving outcomes during STEMI may depend on exploring therapeutics that modulate the pathophysiology of microvascular damage during ischemia-reperfusion injury, a phenomenon whose effects evolve over hours to days. We speculate that the dynamic nature of the no-reflow phenomenon may be an explanation for these disappointing results with the intravenous antiplatelet agents. We hope that appreciation for what has not worked in this domain may direct future research efforts to focus on novel pathways. Myocardial ischemia and reperfusion injury are very much still a lingering issue. Despite significant improvements in door-to-balloon times, rates of in-hospital mortality for STEMI remain unchanged. Outcomes following successfully reperfused STEMI are likely determined by the initial size of myocardial necrosis (ie, cardiomyocyte death during the period of ongoing ischemia), patency of the infarct-related epicardial coronary artery, possible reperfusion injury, the microvascular no-reflow phenomenon, and adverse remodeling after infarction.

The significance of ST-elevation in aVL in anterolateral myocardial infarction: An assessment by cardiac magnetic resonance imaging.

BACKGROUND: Anterolateral myocardial infarction (MI) is traditionally defined on the electrocardiogram by ST-elevation (STE) in I, aVL, and the precordial leads. Traditional literature holds STE in lead aVL to be associated with occlusion proximal to the first diagonal branch of the left anterior descending coronary artery. However, concomitant ischemia of the inferior myocardium may theoretically lead to attenuation of STE in aVL. We compared segmental distribution of myocardial area at risk (MaR) in patients with and without STE in aVL. METHODS: We identified patients in the MITOCARE study presenting with a first acute MI and new STE in two contiguous anterior leads from V1 to V6 , with or without aVL STE. Patients underwent cardiac magnetic resonance imaging 3-5 days after acute infarction for quantitative assessment of MaR. RESULTS: A total of 32 patients met inclusion criteria; 13 patients with and 19 without STE in lead aVL. MaR > 20% at the basal anterior segment was seen in 54% of patients with aVL STE, and 11% of those without (p = 0.011). MaR > 20% at the apical inferior segment was seen in 62% and 95% of patients with and without aVL STE, respectively (p = 0.029). The total MaR was not different between groups (44% ± 10% and 39% ± 8.3% respectively, p = 0.15). CONCLUSION: Patients with anterior STEMI and concomitant STE in aVL have less MaR in the apical inferior segment and more MaR in the basal anterior segment.

Correlation of anteroseptal ST elevation with myocardial infarction territories through cardiovascular magnetic resonance imaging.

BACKGROUND: Anteroseptal ST elevation myocardial infarction (STEMI) is traditionally defined on the electrocardiogram (ECG) by ST elevation (STE) in leads V1-V3, with or without involvement of lead V4. It is commonly taught that such infarcts affect the basal anteroseptal myocardial segment. While there are suggestions in the literature that Q waves limited to V1-V4 represent predominantly apical infarction, none have evaluated anteroseptal ST elevation territories. We compared the distribution of the myocardium at risk (MaR) in STEMI patients presenting with STE limited to V1-V4 and those with more extensive STE (V1-V6). METHODS: We identified patients in the MITOCARE study presenting with a first acute STEMI and new STE in at least two contiguous anterior leads from V1 to V6. Patients underwent cardiac magnetic resonance (CMR) imaging three to five days after acute infarction. RESULTS: Thirty-two patients met inclusion criteria. In patients with STE in V1-V4 (n = 20), myocardium at risk (MaR) > 50% was seen in 0%, 85%, 75%, 100%, and 90% in the basal anteroseptal, mid anteroseptal, apical anterior, apical septal segments, and apex, respectively. The group with STE in V1-V6 (n = 12), MaR > 50% was seen in 8%, 83%, 83%, 92%, and 83% of the same segments. CONCLUSIONS: Patients with acute STEMI and STE in leads V1-V4, exhibit MaR in predominantly apical territories and rarely in the basal anteroseptum. We found no evidence to support existence of isolated basal anteroseptal or septal STEMI. "Anteroapical" infarction is a more precise description than "anteroseptal" infarction for acute STEMI patients exhibiting STE in V1-V4.

Therapeutic Plasma Exchange for Urgent Rivaroxaban Reversal.

Direct oral anticoagulants, which include the factor Xa inhibitor rivaroxaban, have some advantages over vitamin K antagonists in regard to stroke prevention in patients with atrial fibrillation. However, no antidotes to reverse the effect of oral anticoagulants are commercially available, which can complicate treating patients in whom reversal is urgent. We faced this challenge in a kidney transplant candidate, a 65-year-old man with end-stage renal disease who had been taking rivaroxaban for paroxysmal atrial fibrillation. When a deceased-donor kidney became available, we needed to rapidly reduce the patient's bleeding risk, while minimizing the cold ischemic time of the donor kidney. Therefore, we decided to take an experimental approach and perform therapeutic plasma exchange. The patient's plasma anti-factor Xa level decreased from 0.4 IU/mL immediately before treatment to 0.21 IU/mL afterward, indicating that rivaroxaban had been actively removed from circulation. Waste fluid showed significant anti-Xa activity, indicating that the risk of rebound anticoagulation had been mitigated. The patient subsequently underwent successful kidney transplantation. To our knowledge, this is the first report of therapeutic plasma exchange to reverse the effects of rivaroxaban in a patient undergoing urgent surgery. This treatment may also be suitable for patients who have life-threatening, large-volume bleeding, especially in the presence of substantial kidney or liver dysfunction.

Paraplegia After Laparotomy for Large Bowel Obstruction: A Case Report.

We report persistent postoperative paraplegia on recovery from anesthesia after emergent exploratory laparotomy for large bowel obstruction in a cachectic patient with an abdominal aortic aneurysm. Postoperative cervical, thoracic, and lumbar spine magnetic resonance imaging revealed only cervical spinal stenosis. We hypothesize that intraoperative embolization possibly caused by manipulation of an atherosclerotic aorta, and a brief episode of intraoperative hypotension resulted in spinal cord ischemia. This report highlights the importance of maintaining intraoperative hemodynamic stability and careful handling of the abdominal aorta, especially in underweight patients with an abdominal aortic aneurysm.