Pharmacotherapy for Coronary Artery Disease and Acute Coronary Syndrome in the Aging Population.

PURPOSE OF REVIEW: To provide a comprehensive summary of relevant studies and evidence concerning the utilization of different pharmacotherapeutic and revascularization strategies in managing coronary artery disease and acute coronary syndrome specifically in the older adult population. RECENT FINDINGS: Approximately 30% to 40% of hospitalized patients with acute coronary syndrome are older adults, among whom the majority of cardiovascular-related deaths occur. When compared to younger patients, these individuals generally experience inferior clinical outcomes. Most clinical trials assessing the efficacy and safety of various therapeutics have primarily enrolled patients under the age of 75, in addition to excluding those with geriatric complexities. In this review, we emphasize the need for a personalized and comprehensive approach to pharmacotherapy for coronary heart disease and acute coronary syndrome in older adults, considering concomitant geriatric syndromes and age-related factors to optimize treatment outcomes while minimizing potential risks and complications. In the realm of clinical practice, cardiovascular and geriatric risks are closely intertwined, with both being significant factors in determining treatments aimed at reducing negative outcomes and attaining health conditions most valued by older adults.

Electronic ventricular pacing at the end of the QRS complex: Is it abnormal?

An 82-year-old man with ischemic cardiomyopathy, heart failure with reduced ejection fraction and Medtronic biventricular ICD presented with shortness of breath. His ECG is presented with shortness of breath. ECG shows atrial sensed, electronic ventricular pacing. At the end of each QRS complex there is another pacemaker stimulus. This represents typical case of cardiac contractility modulation therapy and not pacemaker malfunction.

Why do we keep missing left circumflex artery myocardial infarctions?

BACKGROUND: Diagnosis of left circumflex artery (LCx) myocardial infarctions via 12­lead electrocardiogram (ECG) has posed a challenge to healthcare professionals for many years. METHODS AND RESULTS: A retrospective observational study was performed to analyze patients admitted with myocardial infarction. The study used electronic medical records and specific ICD-10 codes to identify eligible patients, resulting in 2032 encounters. After independent adjudication of cardiac biomarkers, coronary angiography, and electrocardiographic changes, a final patient population of 58 encounters with acute occlusion myocardial infarction (OMI) with a culprit LCx lesion was established. OMI was defined as a lesion with either thrombolysis in myocardial infarction flow (TIMI) 0-2 or TIMI 3 with Troponin I > 1 ng/mL (Reference range 0.00-0.03 ng/mL). ECGs of these patients were then independently evaluated and grouped into 8 different classifications based on the presence or absence of ST elevation and/or depression in corresponding leads. ECG patterns and anatomical characteristics (proximal or distal to the first obtuse marginal artery) of the LCx lesions were then correlated. The appropriateness of triage and delay in reperfusion therapy were also assessed. Those with a left dominant or codominant circulation, and with LCx lesions proximal to the first obtuse marginal artery, were more likely to present with no or subtle ST-segment changes that led to delays in reperfusion therapy. CONCLUSIONS: Patients with left or codominant coronary artery circulation, with OMI proximal to the first obtuse marginal artery, may be less likely to have "classic" findings of ST-segment elevation on ECG due to cancellation forces in the limb leads.

Do We Still Need Aspirin in Coronary Artery Disease?

Aspirin has for some time been used as a first-line treatment for acute coronary syndromes, including ST-elevation myocardial infarction, for secondary prevention of established coronary disease, and for primary prevention in patients at risk of coronary artery disease. Although aspirin has been in use for decades, the available evidence for its efficacy largely predates the introduction of other drugs, such as statins and P2Y12 inhibitors. Based on recent trials, the recommendation for aspirin use as primary prevention has been downgraded. In addition, P2Y12 inhibitors given as a single antiplatelet therapy have been associated with a lower incidence of bleeding than dual antiplatelet therapy in combination with aspirin in patients with stable and unstable coronary artery disease. The aim of this review is to discuss the role of aspirin considering the available evidence for primary prevention, secondary prevention for stable coronary artery disease or acute coronary syndromes, and after percutaneous coronary intervention or coronary artery bypass revascularization.

Effects of Dapagliflozin on Myocardial Gene Expression in BTBR Mice with Type 2 Diabetes.

BACKGROUND: Dapagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, is approved for the treatment of type 2 diabetes, heart failure, and chronic kidney disease. DAPA-HF and DELIVER trial results demonstrate that the cardiovascular protective effect of dapagliflozin extends to non-diabetic patients. Hence, the mechanism-of-action may extend beyond glucose-lowering and is not completely elucidated. We have previously shown that dapagliflozin reduces cardiac hypertrophy, inflammation, fibrosis, and apoptosis and increases ejection fraction in BTBR mice with type 2 diabetes. METHODS: We conducted a follow-up RNA-sequencing study on the heart tissue of these animals and performed differential expression and Ingenuity Pathway analysis. Selected markers were confirmed by RT-PCR and Western blot. RESULTS: SGLT2 had negligible expression in heart tissue. Dapagliflozin improved cardiac metabolism by decreasing glycolysis and pyruvate utilization enzymes, induced antioxidant enzymes, and decreased expression of hypoxia markers. Expression of inflammation, apoptosis, and hypertrophy pathways was decreased. These observations corresponded to the effects of dapagliflozin in the clinical trials.

Left septal fascicular block: Evidence, causes, and diagnostic criteria.

The existence of a tetrafascicular intraventricular conduction system is widely accepted by researchers. In this review, we have updated the criteria for left septal fascicular block (LSFB) and the differential diagnosis of prominent anterior QRS forces. More and more evidence points to the fact that the main cause of LSFB is critical proximal stenosis of the left anterior descending coronary artery before its first septal perforator branch. The most important characteristic of LSFB that has been incorporated in the corresponding diagnostic electrocardiographic criteria is its transient/intermittent nature mostly observed in clinical scenarios of acute (ie, acute coronary syndrome including vasospastic angina) or chronic (ie, exercise-induced ischemia) ischemic coronary artery disease. In addition, the phenomenon proved to be phase 4 bradycardia rate dependent and induced by early atrial extrastimulus. Finally, we believe that intermittent LSFB has the same clinical significance as "Wellens syndrome" and the "de Winter pattern" in the acute coronary syndrome scenario.

Dual Antiplatelet Therapy: A Concise Review for Clinicians.

Dual antiplatelet therapy (DAPT) combines two antiplatelet agents to decrease the risk of thrombotic complications associated with atherosclerotic cardiovascular diseases. Emerging data about the duration of DAPT is being published continuously. New approaches are trying to balance the time, benefits, and risks for patients taking DAPT for established cardiovascular diseases. Short-term dual DAPT of 3-6 months, or even 1 month in high-bleeding risk patients, is equivalent in terms of efficacy and effectiveness compared to long-term DAPT for patients who experienced percutaneous coronary intervention in an acute coronary syndrome setting. Prolonged DAPT beyond 12 months reduces stent thrombosis, major adverse cardiovascular events, and myocardial infarction rates but increases bleeding risk. Extended DAPT does not significantly benefit stable coronary artery disease patients in reducing stroke, myocardial infarction, or cardiovascular death. Ticagrelor and aspirin reduce cardiovascular events in stable coronary artery disease with diabetes but carry a higher bleeding risk. Antiplatelet therapy duration in atrial fibrillation patients after percutaneous coronary intervention depends on individual characteristics and bleeding risk. Antiplatelet therapy is crucial for post-coronary artery bypass graft and transcatheter aortic valve implantation; Aspirin (ASA) monotherapy is preferred. Antiplatelet therapy duration in peripheral artery disease depends on the scenario. Adding vorapaxar and cilostazol may benefit secondary prevention and claudication, respectively. Carotid artery disease patients with transient ischemic attack or stroke benefit from antiplatelet therapy and combining ASA and clopidogrel is more effective than ASA alone. The optimal duration of DAPT after carotid artery stenting is uncertain. Resistance to ASA and clopidogrel poses an incremental risk of deleterious cardiovascular events and stroke. The selection and duration of antiplatelet therapy in patients with cardiovascular disease requires careful consideration of both efficacy and safety outcomes. The use of combination therapies may provide added benefits but should be weighed against the risk of bleeding. Further research and clinical trials are needed to optimize antiplatelet treatment in different patient populations and clinical scenarios.

Circular RNA as Therapeutic Targets in Atherosclerosis: Are We Running in Circles?

Much attention has been paid lately to harnessing the diagnostic and therapeutic potential of non-coding circular ribonucleic acids (circRNAs) and micro-RNAs (miRNAs) for the prevention and treatment of cardiovascular diseases. The genetic environment that contributes to atherosclerosis pathophysiology is immensely complex. Any potential therapeutic application of circRNAs must be assessed for risks, benefits, and off-target effects in both the short and long term. A search of the online PubMed database for publications related to circRNA and atherosclerosis from 2016 to 2022 was conducted. These studies were reviewed for their design, including methods for developing atherosclerosis and the effects of the corresponding atherosclerotic environment on circRNA expression. Investigated mechanisms were recorded, including associated miRNA, genes, and ultimate effects on cell mechanics, and inflammatory markers. The most investigated circRNAs were then further analyzed for redundant, disparate, and/or contradictory findings. Many disparate, opposing, and contradictory effects were observed across experiments. These include levels of the expression of a particular circRNA in atherosclerotic environments, attempted ascertainment of the in toto effects of circRNA or miRNA silencing on atherosclerosis progression, and off-target, cell-specific, and disease-specific effects. The high potential for detrimental and unpredictable off-target effects downstream of circRNA manipulation will likely render the practice of therapeutic targeting of circRNA or miRNA molecules not only complicated but perilous.

Interpreting the ECG in patients with chest pain and right bundle branch block: A case report.

A patient with right bundle branch block (RBBB) presented with chest pain. An ECG showed ST-elevation in leads V1, V2, and aVR, with widespread ST-depression in leads II, aVF, I, aVL, and V4-6. The initial ECG interpretation missed ST-elevation myocardial infarction (STEMI), as ST-elevation thresholds were not reached. Non-urgent angiography showed severe left anterior descending artery stenosis requiring percutaneous coronary intervention. The course was complicated by cardiac arrest necessitating resuscitation and dual chamber pacemaker placement with left bundle branch pacing. This case report outlines the deficiencies of the current voltage criteria for identification of anterior STEMI in patients with RBBB.

Machine learning for ECG diagnosis and risk stratification of occlusion myocardial infarction.

Patients with occlusion myocardial infarction (OMI) and no ST-elevation on presenting electrocardiogram (ECG) are increasing in numbers. These patients have a poor prognosis and would benefit from immediate reperfusion therapy, but, currently, there are no accurate tools to identify them during initial triage. Here we report, to our knowledge, the first observational cohort study to develop machine learning models for the ECG diagnosis of OMI. Using 7,313 consecutive patients from multiple clinical sites, we derived and externally validated an intelligent model that outperformed practicing clinicians and other widely used commercial interpretation systems, substantially boosting both precision and sensitivity. Our derived OMI risk score provided enhanced rule-in and rule-out accuracy relevant to routine care, and, when combined with the clinical judgment of trained emergency personnel, it helped correctly reclassify one in three patients with chest pain. ECG features driving our models were validated by clinical experts, providing plausible mechanistic links to myocardial injury.

Machine Learning for the ECG Diagnosis and Risk Stratification of Occlusion Myocardial Infarction at First Medical Contact.

Patients with occlusion myocardial infarction (OMI) and no ST-elevation on presenting ECG are increasing in numbers. These patients have a poor prognosis and would benefit from immediate reperfusion therapy, but we currently have no accurate tools to identify them during initial triage. Herein, we report the first observational cohort study to develop machine learning models for the ECG diagnosis of OMI. Using 7,313 consecutive patients from multiple clinical sites, we derived and externally validated an intelligent model that outperformed practicing clinicians and other widely used commercial interpretation systems, significantly boosting both precision and sensitivity. Our derived OMI risk score provided superior rule-in and rule-out accuracy compared to routine care, and when combined with the clinical judgment of trained emergency personnel, this score helped correctly reclassify one in three patients with chest pain. ECG features driving our models were validated by clinical experts, providing plausible mechanistic links to myocardial injury.

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.

Right Bundle Branch and Bifascicular Blocks: Insensitive Prognostic Indicators for Acute Myocardial Infarction.

The clinical significance of right bundle branch block (RBBB) or bifascicular block (BFB) in the setting of acute myocardial infarction (AMI) is uncertain. RBBB was found in 211 of 7,626 patients (2.8%), presenting to the ED (emergency department) with chest pain, of which 18 (8.5%) also had acute coronary syndrome (ACS). Incidences of ACS were not significantly different between new or presumed new RBBB and prior known RBBB or new or presumed new BFB and prior known BFB. In 2 patients, baseline ST-segment depression in leads V1-3 masked anterior ST-elevation detected on electrocardiogram (ECG). In opposition to the guidelines, the presence of RBBB or BFB does not appear to offer any clinical utility when evaluating patients with suspected AMI. Patients with suspected AMI who present with RBBB and any ST-elevation in leads V1-3 should be considered for emergent coronary angiography rather than RBBB alone.

Recombinant Apyrase (AZD3366) Against Myocardial Reperfusion Injury.

PURPOSE: Recombinant apyrase (AZD3366) increases adenosine production and ticagrelor inhibits adenosine reuptake. We investigated whether intravenous AZD3366 before reperfusion reduces myocardial infarct size (IS) and whether AZD3366 and ticagrelor have additive effects. METHODS: Sprague-Dawley rats underwent 30 min ischemia. At 25 min of ischemia, animals received intravenous AZD3366 or vehicle. Additional animals received intravenous CGS15943 (an adenosine receptor blocker) or intraperitoneal ticagrelor. At 24 h reperfusion, IS was assessed by triphenyltetrazolium chloride. Other rats were subjected to 30 min ischemia followed by 1 h or 24 h reperfusion. Myocardial samples were assessed for adenosine levels, RT-PCR, and immunoblotting. RESULTS: AZD3366 and ticagrelor reduced IS. The protective effect was blocked by CGS15943. The effect of AZD3366 + ticagrelor was significantly greater than AZD3366. One hour after infarction, myocardial adenosine levels significantly increased with AZD3366, but not with ticagrelor. In contrast, 24 h after infarction, adenosine levels were equally increased by AZD3366 and ticagrelor, and levels were higher in the AZD3366 + ticagrelor group. One hour after reperfusion, AZD3366 and ticagrelor equally attenuated the increase in interleukin-15 (an early inflammatory marker after ischemic cell death) levels, and their combined effects were additive. AZD3366, but not ticagrelor, significantly attenuated the increase in RIP1, RIP3, and P-MLKL (markers of necroptosis) 1 h after reperfusion. AZD3366, but not ticagrelor, significantly attenuated the increase in IL-6 and GSDMD-N (markers of pyroptosis) 1 h after reperfusion. At 24 h of reperfusion, both agents equally attenuated the increase in these markers, and their effects were additive. CONCLUSIONS: AZD3366 attenuated inflammation, necrosis, necroptosis, and pyroptosis and limited IS. The effects of AZD3366 and ticagrelor were additive.