The Impact of Microvascular Resistance Reserve on the Outcome of Patients With STEMI.

BACKGROUND: Microvascular resistance reserve (MRR) can characterize coronary microvascular dysfunction (CMD); however, its prognostic impact in ST-segment elevation myocardial infarction (STEMI) patients remains undefined. OBJECTIVES: This study sought to investigate the prevalence of CMD in STEMI patients and to elucidate the prognostic performance of MRR. METHODS: This prospective cohort study enrolled 210 STEMI patients with multivessel disease who underwent successful revascularization and returned at 3 months for coronary physiology assessments with bolus thermodilution. The prevalence of CMD (MRR <3) and the association between MRR and major adverse cardiovascular and cerebrovascular events (MACCEs) at 12 months were investigated. RESULTS: The median age of patients was 65 years, and 59.5% were men. At the 3-month follow-up, 56 patients (27%) had CMD (MRR <3.0). The number of MACCEs at 12 months was higher in patients with vs without CMD (48.2% vs 11.0%; P < 0.001). MRR was independently associated with 12-month MACCEs (HR: 0.45 per unit increase; 95% CI: 0.31-0.67; P < 0.001) and with stroke, heart failure, and poorer recovery in left ventricular systolic function. The areas under the receiver-operating characteristic curves for predicting MACCEs at 12 months with fractional flow reserve, coronary flow reserve (CFR), the index of microvascular resistance (IMR), and MRR were 0.609, 0.762, 0.781, and 0.743, respectively. The prognostic performance of CFR, IMR, and MRR were all comparable. CONCLUSIONS: The novel parameter MRR is a prognostic marker of MACCEs in STEMI patients with a comparable performance to CFR and IMR. (Impact of TMAO Serum Levels on Hyperemic IMR in STEMI Patients [TAMIR]; NCT05406297).

Impact of Coronary Microvascular Dysfunction on Functional Left Ventricular Remodeling and Diastolic Dysfunction.

BACKGROUND: Coronary microvascular dysfunction (CMD) is a common complication of ST-segment-elevation myocardial infarction (STEMI) and can lead to adverse cardiovascular events. Whether CMD after STEMI is associated with functional left ventricular remodeling (FLVR) and diastolic dysfunction, has not been investigated. METHODS AND RESULTS: This is a nonrandomized, observational, prospective study of patients with STEMI with multivessel disease. Coronary flow reserve and index of microcirculatory resistance of the culprit vessel were measured at 3 months post-STEMI. CMD was defined as index of microcirculatory resistance ≥25 or coronary flow reserve <2.0 with a normal fractional flow reserve. We examined the association between CMD, LV diastolic dysfunction, FLVR, and major adverse cardiac events at 12-month follow-up. A total of 210 patients were enrolled; 59.5% were men, with a median age of 65 (interquartile range, 58-76) years. At 3-month follow-up, 57 patients (27.14%) exhibited CMD. After 12 months, when compared with patients without CMD, patients with CMD had poorer LV systolic function recovery (-10.00% versus 8.00%; P<0.001), higher prevalence of grade 2 LV diastolic dysfunction (73.08% versus 1.32%; P<0.001), higher prevalence of group 3 or 4 FLVR (11.32% versus 7.28% and 22.64% versus 1.99%, respectively; P<0.001), and higher incidence of major adverse cardiac events (50.9% versus 9.8%; P<0.001). Index of microcirculatory resistance was independently associated with LV diastolic dysfunction and adverse FLVR. CONCLUSIONS: CMD is present in ≈1 of 4 patients with STEMI during follow-up. Patients with CMD have a higher prevalence of LV diastolic dysfunction, adverse FLVR, and major adverse cardiac events at 12 months compared with those without CMD. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT05406297.

Clinical characteristics and statin eligibility of patients under 50 with ST-elevation myocardial infarction.

AIMS: This study seeks to understand the clinical characteristics, risk factors, and statin eligibility of younger adults who present with STEMI. METHODS: We performed a retrospective analysis of a prospective cohort of STEMI patients <50 years. Baseline characteristics, medical history, prior medications, drug use, lipid profiles, cardiovascular risk factors were examined. Ten-year ASCVD risk was calculated utilizing the Pooled Cohort Equations. Statin eligibility was determined according to the 2019 American College of Cardiology (ACC)/American Heart Association (AHA) and the 2022 US Preventive Services Task Force (USPSTF) guidelines. RESULTS: Six hundred and thirty-five individuals were included, the majority were men (82.4%) and white (89%), with a median age was 46.9 [42.0-48.0]. The most prevalent risk factors were current smoking (59%), hyperlipidemia (44%), and hypertension (37%). Drug use was rare (8.3%). Preventative medication use was low, aspirin was the most common (14%), followed by ACE inhibitors/ARBs (12%), statins (11%), and beta-blockers (9.1%). Mean HDL-C was low at 36.4 ± 12.0 mg/dL, while mean LDL was unremarkable at 112.4 ± 37.9 mg/dL. According to the 2019 ACC/AHA guidelines, 45.5% were classified as statin recommended, 8.7% were classified as statin considered, and 45.8% were classified as statin not recommended. According to the 2022 USPSTF guidelines, 29% were classified as statin recommended, 12.4% were classified as statin considered, and 58.6% were classified as statin not recommended. CONCLUSIONS: Younger adults with STEMI exhibit high rates of tobacco use and low rates of preventative medications use. Approximately half of the cohort did not meet criteria for statin initiation.

Coronary artery calcium and the risk of a cardiovascular events and mortality in younger adults: a meta-analysis.

AIMS: ACC/AHA 2019 prevention guidelines recommend utilizing coronary artery calcium (CAC) to stratify cardiovascular risk in selected cases. However, data regarding CAC and risk in younger adults is less robust due to the lower prevalence of CAC and lower incidence of events. The objective of this meta-analysis is to determine the ability of CAC to predict the risk of cardiovascular events and mortality in adults less than 50. METHODS: PubMed and Cochrane CENTRAL databases were electronically searched through May 2022 for studies with a primary prevention cohort under age 55 who underwent CAC scoring. RESULTS: Six observational studies with a total of 45,919 individuals with an average age of 43.1 and mean follow-up of 12.1 years were included. The presence of CAC was associated with an increased risk of adverse events (pooled hazard ratio (HR) = 1.80, 95% confidence interval (CI) 1.26-2.56, P = 0.012, I2 = 65.5). Compared to a CAC of 0, a CAC of 1-100 did carry an increased risk of cardiovascular events (pooled HR = 1.85, 95% CI 1.08-3.16, p = 0.0248, I2 = 50.3), but not mortality (pooled HR = 1.20, 95% CI 0.85-1.69, p = 0.2917), while a CAC > 100 did carry an increased risk of cardiovascular events (pooled HR = 6.57, 95% CI 3.23-13.36, p < 0.0001, I2 = 72.6) and mortality (pooled HR = 2.91, 95% CI 2.23-3.80, p < 0.0001) . CONCLUSIONS: In a meta-analysis of younger adults undergoing CAC scoring, a CAC of 1-100 was associated with a higher likelihood of cardiovascular events, while a CAC>100 was associated with a higher likelihood of cardiovascular events and mortality.

This paper compiles prior studies into a meta-analysis to clarify the ability of coronary artery calcium (CAC) to predict cardiovascular risk and mortality risk in adults < 55 years. A mildly elevated CAC (1-100) in adults < 55 likely has an increased cardiovascular risk but does not appear to have an increased mortality risk.A moderately or highly elevated CAC (>100) in adults < 55 has a substantial increase in cardiovascular risk and mortality risk.

The impact of primary percutaneous coronary intervention strategies during ST-elevation myocardial infarction on the prevalence of coronary microvascular dysfunction.

Coronary microvascular dysfunction (CMD) is a common complication of ST-segment elevation myocardial infarction (STEMI) and can lead to adverse cardiovascular events. This is a non-randomized, observational, prospective study of STEMI patients with multivessel disease who underwent primary PCI, grouped based on whether they underwent balloon pre-dilatation stenting or direct stenting of the culprit lesion. Coronary physiology measurements were performed 3 months post-PCI including coronary flow reserve (CFR) and index of microcirculatory resistance (IMR) measurements at the culprit vessel. The primary endpoint was the prevalence of CMD at 3 months, defined as IMR ≥ 25 or CFR < 2.0 with a normal fractional flow reserve. Secondary endpoints included major adverse cardiovascular events (MACE) at 12 months. Two hundred ten patients were enrolled; most were men, 125 (59.5%), with a median age of 65 years. One hundred twelve (53.2%) underwent balloon pre-dilatation before stenting, and 98 (46.7%) underwent direct stenting. The prevalence of CMD at 3 months was lower in the direct stenting group than in the balloon pre-dilatation stenting group (12.24% vs. 40.18%; p < 0.001). Aspiration thrombectomy and administration of intracoronary glycoprotein IIb/IIIa inhibitors were associated with lower odds of CMD (OR = 0.175, p = 0.001 and OR = 0.113, p = 0.001, respectively). Notably, MACE in patients who underwent direct stenting was lower than in those who underwent balloon pre-dilatation before stenting (14.29% vs. 26.79%; p = 0.040). In STEMI patients with multivessel disease, direct stenting of the culprit lesion, aspiration thrombectomy and administration of intracoronary glycoprotein IIb/IIIa inhibitors were associated with a lower prevalence of CMD at 3 months and lower incidence of MACE at 12 months compared with balloon pre-dilatation stenting.This trial is registered at https://ichgcp.net/clinical-trials-registry/NCT05406297 .

The Impact of Trimethylamine N-Oxide and Coronary Microcirculatory Dysfunction on Outcomes following ST-Elevation Myocardial Infarction.

INTRODUCTION: Persistent coronary microcirculatory dysfunction (CMD) and elevated trimethylamine N-oxide (TMAO) levels after ST-elevation myocardial infarction (STEMI) may drive negative structural and electrical cardiac remodeling, resulting in new-onset atrial fibrillation (AF) and a decrease in left ventricular ejection fraction (LVEF). AIMS: TMAO and CMD are investigated as potential predictors of new-onset AF and left ventricular remodeling following STEMI. METHODS: This prospective study included STEMI patients who had primary percutaneous coronary intervention (PCI) followed by staged PCI three months later. Cardiac ultrasound images were obtained at baseline and after 12 months to assess LVEF. Coronary flow reserve (CFR), and index of microvascular resistance (IMR) were assessed using the coronary pressure wire during the staged PCI. Microcirculatory dysfunction was defined as having an IMR value ≥25 U and CFR value <2.5 U. RESULTS: A total of 200 patients were included in the study. Patients were categorized according to whether or not they had CMD. Neither group differed from the other with regards to known risk factors. Despite making up only 40.5% of the study population, females represented 67.4% of the CMD group p < 0.001. Similarly, CMD patients had a much higher prevalence of diabetes than those without CMD (45.7% vs. 18.2%; p < 0.001). At the one-year follow-up, the LVEF in the CMD group had decreased to significantly lower levels than those in the non-CMD group (40% vs. 50%; p < 0.001), whereas it had been higher in the CMD group at baseline (45% vs. 40%; p = 0.019). Similarly, during the follow-up, the CMD group had a greater incidence of AF (32.6% vs. 4.5%; p < 0.001). In the adjusted multivariable analysis, the IMR and TMAO were associated with increased odds of AF development (OR: 1.066, 95% CI: 1.018-1.117, p = 0.007), and (OR: 1.290, 95% CI: 1.002-1.660, p = 0.048), respectively. Similarly, elevated levels of IMR and TMAO were linked with decreased odds of LVEF improvement, while higher CFR values are related to a greater likelihood of LVEF improvement. CONCLUSIONS: CMD and elevated TMAO levels were highly prevalent three months after STEMI. Patients with CMD had an increased incidence of AF and a lower LVEF 12 months after STEMI.

Estimated versus observed 10-year atherosclerotic cardiovascular event rates in a rural population-based health initiative: The Heart of New Ulm Project.

Objective: Assess discrepancy between estimated 10-year atherosclerotic cardiovascular disease (ASCVD) risk and observed 10-year event rates in a rural population participating in cardiovascular health initiative. Methods: The study included a rural sample of individuals participating in the Heart of New Ulm (HONU), a population-based health initiative aimed at reducing ASCVD risk in a rural community. HONU conducted over 100 baseline screening events with 5221 individuals participating in 2009. For this analysis, we included participants who were aged 40-79 years, free of ASCVD at baseline, and had adequate data to calculate 10-year ASCVD risk. Electronic health record data and state death records were used to determine rates of non-fatal myocardial infarction and stroke, and ASCVD death from 2010-2019. ASCVD event rates were compared to estimated 10-year risks calculated using the Pooled Cohort Equations, stratified by sex and clinically relevant risk categories. Results: The sample (n = 2819, mean ± SD age 56.1 ± 9.9 years, 59.6% female) had a low prevalence of tobacco use (8.1% current smokers) and diabetes (6.5%) and a high prevalence of hypertension (44.4%) and hyperlipidemia (56.6%). The median estimated 10-year ASCVD risk for the entire sample was 5.7% (IQR 2.3-13.5%) with an observed 10-year ASCVD event rate of 3.4%. The largest gap between observed and estimated risk was in those at intermediate/high (≥7.5%) ASCVD risk (median 10-year risk 15.8% [IQR 10.4-29.0], observed ASCVD event rate 6.4%). Conclusio: In a sample of rural participants exposed to a multifaceted ASCVD prevention initiative, observed rates of ASCVD were substantially lower compared to estimated ASCVD risk. The potential for significantly lower than predicted ASCVD event rates in certain populations should be included in the clinician-patient risk discussion.

A prospective observational study on impact of epinephrine administration route on acute myocardial infarction patients with cardiac arrest in the catheterization laboratory (iCPR study).

BACKGROUND: Epinephrine is routinely utilized in cardiac arrest; however, it is unclear if the route of administration affects outcomes in acute myocardial infarction patients with cardiac arrest. OBJECTIVES: To compare the efficacy of epinephrine administered via the peripheral intravenous (IV), central IV, and intracoronary (IC) routes. METHODS: Prospective two-center pilot cohort study of acute myocardial infarction patients who suffered cardiac arrest in the cardiac catheterization laboratory during percutaneous coronary intervention. We compared the outcomes of patients who received epinephrine via peripheral IV, central IV, or IC. RESULTS: 158 participants were enrolled, 48 (30.4%), 50 (31.6%), and 60 (38.0%) in the central IV, IC, and peripheral IV arms, respectively. Peripheral IV epinephrine administration route was associated with lower odds of achieving return of spontaneous circulation (ROSC, odds ratio = 0.14, 95% confidence interval = 0.05-0.36, p < 0.0001) compared with central IV and IC administration. (There was no difference between central IV and IC routes; p = 0.9343.) The odds of stent thrombosis were significantly higher with the IC route (IC vs. peripheral IV OR = 4.6, 95% CI = 1.5-14.3, p = 0.0094; IC vs. central IV OR = 6.0, 95% CI = 1.9-19.2, p = 0.0025). Post-ROSC neurologic outcomes were better for central IV and IC routes when compared with peripheral IV. CONCLUSION: Epinephrine administration via central IV and IC routes was associated with a higher rate of ROSC and better neurologic outcomes compared with peripheral IV administration. IC administration was associated with a higher risk of stent thrombosis. Trial registration This trial is registered at NCT05253937 .

A comparison of risk scores' long-term predictive abilities for patients diagnosed with ST elevation myocardial infarction who underwent early percutaneous coronary intervention.

Objective. To compare the long-term (5 year) prognostic values of commonly used risk scores on major adverse cardiovascular events (MACE) in a cohort of patients who underwent primary PCI for STEMI. Design. We created a composite endpoint of MACE, defined as the occurrence of any of the following events within 5 years: ischemic or hemorrhagic stroke, target vessel revascularization, nonfatal myocardial infarction, cardiovascular death. We dichotomized risk scores into high risk and not high risk according to the literature's pre-existing cutoffs as follows: GRACE score >127 = high risk, SYNTAX I score ≥33 = high risk, SYNTAX II ≥32 high risk, TIMI >8 = high risk. We utilized the area under the receiver operating characteristic curve (AUC) as the metric for predictive ability. Results. There were 768 patients in this study and 416 (54.2%), 209 (27.2%), 511 (66.5%), and 74 (9.6%) were at high risk according to the GRACE, SYNTAX I, SYNTAX II, and TIMI scores, respectively. The AUCs for 5-year MACE were 0.54 (95% confidence interval (CI): 0.49-0.59, p = .0947), 0.79 (95% CI: 0.75-0.83, p < .0001), 0.58 (95% CI: 0.54-0.62, p = .0004), and 0.5 (95% CI: 0.48-0.53, p = .7259), respectively. Conclusion. SYNTAX I score was superior in predicting MACE in patients with STEMI and a high burden of CAD. Utilizing the basal SYNTAX I score in STEMI patients with significant non-culprit CAD may improve risk stratification, decision-making, and outcomes.

Coronary Artery Calcium for Risk Assessment in Young Adults.

PURPOSE OF REVIEW: To review the prognostic significance and clinical utility of coronary artery calcium (CAC) for risk assessment for atherosclerotic cardiovascular disease (ASCVD) in younger adults. RECENT FINDINGS: Data from over 3000 young adults (mean age of 40.3 ± 3.6 followed for 12.5 years) in the CARDIA registry found that in an asymptomatic, community representative sample, there was a low prevalence of CAC (~ 10%) but those with CAC had an exponential increase in CAC over time and significantly higher rates of ASCVD events. Alternatively, data from the CAC consortium analyzed 22,346 asymptomatic individuals undergoing CAC for clinical indications (mean age 43.5 ± 4.5 years, followed for 13 ± 4 years) and found a much higher prevalence of CAC at 34% with rates of coronary heart disease mortality that varied significantly according to CAC. In younger adults, CAC provides clear prognostic value and can be considered in select individuals with uncertainties about their ASCVD risk or the benefit of preventive therapies.

Impact of Mineralocorticoid Receptor Gene NR3C2 on the Prediction of Functional Classification of Left Ventricular Remodeling and Arrhythmia after Acute Myocardial Infarction.

Background: The NR3C2 gene encodes the mineralocorticoid receptor, which is present on cardiomyocytes. Prior studies reported an association between the presence of NR3C2 single-nucleotide polymorphisms (SNPs) and an increased cortisol production during a stress response such as acute myocardial infarction (AMI), which may lead to adverse cardiac remodeling. Objective: To study the impact of the NR3C2 rs2070950, rs4635799 and rs5522 gene polymorphisms on left ventricular (LV) remodeling, rhythm and conduction disorders in AMI patients. Methods: A cohort of 301 AMI patients who underwent revascularization was included. SNPs of the NR3C2 gene (rs2070950, rs4635799 and rs5522) were evaluated. A total of 127 AMI patients underwent transthoracic echocardiography follow-up after 72 h and 6 months. Results: The rs2070950 GG genotype and rs4635799 TT genotype were most common in patients who had LV end-diastolic volume increase < 20% and the same or increased LV ejection fraction, indicating a possible protective effect of these SNPs. The rs5522 TT genotype was associated with a higher frequency of arrhythmias, while the presence of at least one rs5522 C allele was associated with a lower risk of arrhythmias. Conclusion: SNPs of the NR3C2 gene appear to correlate with better ventricular remodeling and a reduced rate of arrhythmias post-AMI, possibly by limiting the deleterious effects of cortisol on cardiomyocytes.

Block of branching portion of bundle of His from catheter shaft during ablation of left ventricular outflow tract ventricular premature complexes.

Ventricular premature contractions are often located in the left ventricular outflow tract (LVOT). Components of the normal atrioventricular conduction apparatus are located just below the aortic valve in proximity to the membranous septum, between the noncoronary cusp and right coronary cusp. We present a case of injury to the bundle of His during an ablation of a ventricular premature contraction in the LVOT below the left coronary cusp, remote from the bundle of His, due to pressure from the proximal shaft of the catheter between the noncoronary cusp and the right coronary cusp.

Atrial tachyarrhythmia as a presenting symptom leading to the diagnosis of pulmonary sarcoidosis treated with catheter-based ablation.

A 55-year-old woman was referred for recurrent palpitations. A 48-hour ambulatory cardiac monitor revealed an atrial tachycardia rate up to 170 beats per minute. A subsequent electrophysiology study revealed atrial fibrillation and both typical and atypical atrial flutter. Computed tomography revealed multiple pulmonary nodules, and an endobronchial ultrasound-guided fine-needle aspiration confirmed the diagnosis of pulmonary sarcoidosis. The patient underwent radiofrequency ablation of the cavotricuspid isthmus and left common, right superior, and right inferior pulmonary vein isolation via cryoablation, without recurrent symptoms.

Clozapine-Induced Microseizures, Orofacial Dyskinesia, and Speech Dysfluency in an Adolescent with Treatment Resistant Early Onset Schizophrenia on Concurrent Lithium Therapy.

Clozapine is an atypical antipsychotic used in the treatment of refractory schizophrenia. It has a well-known side effect profile, including agranulocytosis, decreased seizure threshold, and tardive dyskinesia. In addition, numerous case reports have described clozapine-induced stuttering in adults. However, there has been only one previous case report describing it in the adolescent population. In addition, concurrent lithium therapy has been shown to enhance the neurotoxic effects of antipsychotics and lower the seizure threshold. Here, we report on the development of clozapine-induced microseizures, orofacial dyskinesia, and stuttering in a 17-year-old adolescent male with treatment of refractory early onset schizophrenia on clozapine and concurrent lithium therapy. The patient's symptoms of schizophrenia responded well to the clozapine regimen. However, with the escalating dose of clozapine, the patient developed speech dysfluency in the form of stuttering and perioral twitching. An electroencephalogram confirmed seizure activity. Due to similarities with tardive dyskinesia, symptoms of microseizures induced by atypical antipsychotics may not be accurately diagnosed. A multidisciplinary treatment of speech dysfluency is of particular importance in the adolescent schizophrenic patients, who are expected to have longer duration of lifetime exposure to antipsychotics and in whom peer group interaction is crucial for normal personal and social development.

Interleukin-6 and neopterin levels in the serum and saliva of patients with Lichen planus and oral Lichen planus.

BACKGROUND: Lichen planus together with its oral variant is a chronic, inflammatory disease of the skin and the mucosa of unclear aetiology and with an unpredictable course that still poses a major problem in terms of diagnosis and treatment. The objective of this study was to assess the concentrations of interleukin-6 (IL-6) and neopterin in saliva and serum of patients with lichen planus (including reticular and erosive form of oral lichen planus) and to compare them with the concentrations observed in healthy controls. METHODS: The study material comprised serum and saliva samples from 56 patients diagnosed with lichen planus and 56 healthy volunteers. The ELISA test was used to measure concentrations of IL-6 and neopterin in the serum and saliva of the study participants. RESULTS: The concentrations of IL-6 in saliva and serum of patients with lichen planus were significantly higher than in controls (P = 0.0002; P < 0.0001). The difference remains significant after adjustment for gingivitis and age. Patients with atrophic-erosive oral lichen planus had significantly higher IL-6 concentrations in their saliva compared to patients with reticular form of disease (P = 0.01). The concentrations of neopterin were significantly higher in the serum but not in saliva of lichen planus patients vs. controls (P <0.0001). CONCLUSIONS: Serum levels of proinflammatory cytokines IL-6 and neopterin are increased in lichen planus as well as the salivary concentrations of IL-6. The differences observed in IL-6 levels in patients with erosive-atrophic forms of oral lichen planus may indicate a substantial role played by the cytokine in the disease.