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Determining the Cause of Coronary Vasomotor Disorders in Patients With Ischemia and Nonobstructive Coronary Arteries: Design and Rationale of the DISCOVER INOCA Prospective, Multicenter Registry

Shah, Samit M; Tremmel, Jennifer A; Henry, Timothy D; Smilowitz, Nathaniel R; Prasad, Megha; Kobayashi, Yuhei; Henry, Glen A; Samady, Habib; Samuels, Bruce A; Lerman, Amir; Moses, Jeffrey W; Pietras, Cody; Zhang, Zhiyuan; Tirziu, Daniela; Parise, Helen; Cristea, Ecaterina; Chamié, Daniel; Grubman, Daniel; Henrici, Kyna; Matmusaeva, Elzar; Latif, Nida; Cigarroa, Natasha; Lansky, Alexandra J
BACKGROUND/UNASSIGNED:Approximately 30% to 50% of patients who are referred for diagnostic coronary angiography are found to have no obstructive coronary artery disease (CAD). Ischemia and nonobstructive coronary arteries (INOCA) is increasingly recognized and encompasses coronary microvascular dysfunction, vasospastic angina, symptomatic myocardial bridging, and other vasomotor disorders. However, the prevalence of these disorders and whether underlying atherosclerotic plaque burden and morphology affect the long-term outcomes of each physiologic phenotype is unknown. METHODS/UNASSIGNED:The DISCOVER INOCA registry is ongoing at 8 centers in the United States and plans to enroll 500 patients with ischemic heart disease referred for angiography undergoing coronary function testing (CFT). All participants will complete patient-reported outcome measures and undergo protocol-guided angiography, acetylcholine provocation, coronary thermodilution, and intravascular imaging. Follow-up assessments occur at 30 days, 6 months, 1 year, and annually for 5 years. The primary short-term end point is the prevalence of INOCA phenotypes based on physiology and the degree of atherosclerosis based on intravascular ultrasound or optical coherence tomography (intravascular imaging). The primary long-term end point is the incidence of major adverse cardiovascular events, defined as a composite of cardiovascular death, myocardial infarction, hospitalization for cardiovascular causes, or coronary revascularization at a follow-up of 5 years. At the time of this publication, 100 participants have been enrolled. CONCLUSIONS/UNASSIGNED:DISCOVER INOCA is the first prospective study of INOCA patients to integrate anatomic and physiologic measures of disease and correlate them with long-term outcomes. DISCOVER INOCA will report on the prevalence of INOCA phenotypes, the safety of comprehensive invasive CFT, and the impact of testing on diagnoses and medical therapy. Symptoms and cardiovascular adverse events at long-term follow-up will be determined in patients with no obstructive CAD undergoing angiography.
PMCID:11308755
PMID: 39132594
ISSN: 2772-9303
CID: 5726722

Ventricular Arrhythmias After Primary Percutaneous Coronary Intervention for STEMI

Rymer, Jennifer A; Wegermann, Zachary K; Wang, Tracy Y; Li, Shuang; Smilowitz, Nathaniel R; Wilson, B Hadley; Jneid, Hani; Tamis-Holland, Jacqueline E
IMPORTANCE/UNASSIGNED:Currently, mortality risk for patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI) with an uncomplicated postprocedure course is low. Less is known regarding the risk of in-hospital ventricular tachycardia (VT) and ventricular fibrillation (VF). OBJECTIVE/UNASSIGNED:To evaluate the risk of late VT and VF after primary PCI for STEMI. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This cohort study included adults aged 18 years or older with STEMI treated with primary PCI between January 1, 2015, and December 31, 2018, identified in the US National Cardiovascular Data Registry Chest Pain-MI Registry. Data were analyzed from April to December 2020. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Multivariable logistic regression was used to evaluate the risk of late VT (≥7 beat run of VT during STEMI hospitalization ≥1 day after PCI) or VF (any episode of VF≥1 day after PCI) associated with cardiac arrest and associations between late VT or VF and in-hospital mortality in the overall cohort and a cohort with uncomplicated STEMI without prior myocardial infarction or heart failure, systolic blood pressure less than 90 mm Hg, cardiogenic shock, cardiac arrest, reinfarction, or left ventricular ejection fraction (LVEF) less than 40%. RESULTS/UNASSIGNED:A total of 174 126 eligible patients with STEMI were treated with primary PCI at 814 sites in the study; 15 460 (8.9%) had VT or VF after primary PCI, and 4156 (2.4%) had late VT or VF. Among the eligible patients, 99 905 (57.4%) at 807 sites had uncomplicated STEMI. The median age for patients with late VT or VF overall was 63 years (IQR, 55-73 years), and 75.5% were men; the median age for patients with late VT or VF with uncomplicated STEMI was 60 years (IQR, 53-69 years), and 77.7% were men. The median length of stay was 3 days (IQR, 2-7 days) for the overall cohort with late VT or VF and 3 days (IQR, 2-4 days) for the cohort with uncomplicated STEMI with late VT or VF. The risk of late VT or VF was 2.4% (overall) and 1.7% (uncomplicated STEMI). Late VT or VF with cardiac arrest occurred in 674 patients overall (0.4%) and in 117 with uncomplicated STEMI (0.1%). LVEF was the most significant factor associated with late VT or VF with cardiac arrest (adjusted odds ratio [AOR] for every 5-unit decrease ≤40%: 1.67; 95% CI, 1.54-1.85). Late VT or VF events were associated with increased odds of in-hospital mortality in the overall cohort (AOR, 6.40; 95% CI, 5.63-7.29) and the cohort with uncomplicated STEMI (AOR, 8.74; 95% CI, 6.53-11.70). CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this study, a small proportion of patients with STEMI treated with primary PCI had late VT or VF. However, late VT or VF with cardiac arrest was rare, particularly in the cohort with uncomplicated STEMI. This information may be useful when determining the optimal timing for hospital discharge after STEMI.
PMCID:11079687
PMID: 38717772
ISSN: 2574-3805
CID: 5656002

Angiographic Coronary Slow Flow Is Not a Valid Surrogate for Invasively Diagnosed Coronary Microvascular Dysfunction

Mayer, Michael; Allan, Tess; Harkin, Kenneth L; Loftspring, Ethan; Saffari, Seyed E; Reynolds, Harmony R; Paul, Jonathan; Kalathiya, Rohan; Shah, Atman P; Nathan, Sandeep; McCarthy, Mary C; Smilowitz, Nathaniel R; Miner, Steven E S; Blair, John
BACKGROUND:Ischemia with no obstructive coronary arteries is frequently caused by coronary microvascular dysfunction (CMD). Consensus diagnostic criteria for CMD include baseline angiographic slow flow by corrected TIMI (Thrombolysis In Myocardial Infarction) frame count (cTFC), but correlations between slow flow and CMD measured by invasive coronary function testing (CFT) are uncertain. OBJECTIVES/OBJECTIVE:The aim of this study was to investigate relationships between cTFC and invasive CFT for CMD. METHODS:Adults with ischemia with no obstructive coronary arteries underwent invasive CFT with thermodilution-derived baseline coronary blood flow, coronary flow reserve (CFR), and index of microcirculatory resistance (IMR). CMD was defined as abnormal CFR (<2.5) and/or abnormal IMR (≥25). cTFC was measured from baseline angiography; slow flow was defined as cTFC >25. Correlations between cTFC and baseline coronary flow and between CFR and IMR and associations between slow flow and invasive measures of CMD were evaluated, adjusted for covariates. All patients provided consent. RESULTS:Among 508 adults, 49% had coronary slow flow. Patients with slow flow were more likely to have abnormal IMR (36% vs 26%; P = 0.019) but less likely to have abnormal CFR (28% vs 42%; P = 0.001), with no difference in CMD (46% vs 51%). cTFC was weakly correlated with baseline coronary blood flow (r = -0.35; 95% CI: -0.42 to -0.27), CFR (r = 0.20; 95% CI: 0.12 to 0.28), and IMR (r = 0.16; 95% CI: 0.07-0.24). In multivariable models, slow flow was associated with lower odds of abnormal CFR (adjusted OR: 0.53; 95% CI: 0.35 to 0.80). CONCLUSIONS:Coronary slow flow was weakly associated with results of invasive CFT and should not be used as a surrogate for the invasive diagnosis of CMD.
PMCID:11098671
PMID: 38599696
ISSN: 1876-7605
CID: 5655752

Coronary Microvascular Dysfunction Is Associated With a Proinflammatory Circulating Transcriptome in Patients With Nonobstructive Coronary Arteries

Smilowitz, Nathaniel R; Schlamp, Florencia; Hausvater, Anaïs; Joa, Amanda; Serrano-Gomez, Claudia; Farid, Ayman; Hochman, Judith S; Barrett, Tessa; Reynolds, Harmony R; Berger, Jeffrey S
PMID: 38299358
ISSN: 1524-4636
CID: 5627252

Beyond Coronary Artery Disease: Assessing the Microcirculation

Pruthi, Sonal; Siddiqui, Emaad; Smilowitz, Nathaniel R
Ischemic heart disease (IHD) affects more than 20 million adults in the United States. Although classically attributed to atherosclerosis of the epicardial coronary arteries, nearly half of patients with stable angina and IHD who undergo invasive coronary angiography do not have obstructive epicardial coronary artery disease. Ischemia with nonobstructive coronary arteries is frequently caused by microvascular angina with underlying coronary microvascular dysfunction (CMD). Greater understanding the pathophysiology, diagnosis, and treatment of CMD holds promise to improve clinical outcomes of patients with ischemic heart disease.
PMID: 37949533
ISSN: 1558-2264
CID: 5610002

Uncovering Sex Differences in Type 2 Myocardial Infarction: Is Coronary Anatomy Enough? [Editorial]

Smilowitz, Nathaniel R
PMID: 38939380
ISSN: 2772-963x
CID: 5733472

The impact of preoperative stress testing on cardiovascular and surgical care - Does it actually improve outcomes? [Comment]

Smilowitz, Nathaniel R
PMID: 37758564
ISSN: 1873-4529
CID: 5607872

Psychosocial Factors of Women Presenting With Myocardial Infarction With or Without Obstructive Coronary Arteries

Hausvater, Anaïs; Spruill, Tanya M; Xia, Yuhe; Smilowitz, Nathaniel R; Arabadjian, Milla; Shah, Binita; Park, Ki; Giesler, Caitlin; Marzo, Kevin; Thomas, Dwithiya; Wei, Janet; Trost, Jeffrey; Mehta, Puja K; Har, Bryan; Bainey, Kevin R; Zhong, Hua; Hochman, Judith S; Reynolds, Harmony R
BACKGROUND:Women with myocardial infarction (MI) are more likely to have elevated stress levels and depression than men with MI. OBJECTIVES:We investigated psychosocial factors in women with myocardial infarction with nonobstructive coronary arteries (MINOCA) and those with MI and obstructive coronary artery disease (CAD). METHODS:Women with MI enrolled in a multicenter study and completed measures of perceived stress (Perceived Stress Scale-4) and depressive symptoms (Patient Health Questionnaire-2) at the time of MI (baseline) and 2 months later. Stress, depression, and changes over time were compared between MI subtypes. RESULTS:We included 172 MINOCA and 314 MI-CAD patients. Women with MINOCA were younger (age 59.4 years vs 64.2 years; P < 0.001) and more diverse than those with MI-CAD. Women with MINOCA were less likely to have high stress (Perceived Stress Scale-4 ≥6) at the time of MI (51.0% vs 63.0%; P = 0.021) and at 2 months post-MI (32.5% vs 46.3%; P = 0.019) than women with MI-CAD. There was no difference in elevated depressive symptoms (Patient Health Questionnaire-2 ≥2) at the time of MI (36% vs 43%; P = 0.229) or at 2 months post-MI (39% vs 40%; P = 0.999). No differences in the rate of 2-month decline in stress and depression scores were observed between groups. CONCLUSIONS:Stress and depression are common among women at the time of and 2 months after MI. MINOCA patients were less likely to report high stress compared with MI-CAD patients, but the frequency of elevated depressive symptoms did not differ between the 2 groups. Stress and depressive symptoms decreased in both MI-CAD and MINOCA patients over time.
PMID: 37852694
ISSN: 1558-3597
CID: 5684972

Existing Nongated CT Coronary Calcium Predicts Operative Risk in Patients Undergoing Noncardiac Surgeries (ENCORES)

Choi, Daniel Y; Hayes, Dena; Maidman, Samuel D; Dhaduk, Nehal; Jacobs, Jill E; Shmukler, Anna; Berger, Jeffrey S; Cuff, Germaine; Rehe, David; Lee, Mitchell; Donnino, Robert; Smilowitz, Nathaniel R
BACKGROUND:Preoperative cardiovascular risk stratification before noncardiac surgery is a common clinical challenge. Coronary artery calcium scores from ECG-gated chest computed tomography (CT) imaging are associated with perioperative events. At the time of preoperative evaluation, many patients will not have had ECG-gated CT imaging, but will have had nongated chest CT studies performed for a variety of noncardiac indications. We evaluated relationships between coronary calcium severity estimated from previous nongated chest CT imaging and perioperative major clinical events (MCE) after noncardiac surgery. METHODS:We retrospectively identified consecutive adults age ≥45 years who underwent in-hospital, major noncardiac surgery from 2016 to 2020 at a large academic health system composed of 4 acute care centers. All patients had nongated (contrast or noncontrast) chest CT imaging performed within 1 year before surgery. Coronary calcium in each vessel was retrospectively graded from absent to severe using a 0 to 3 scale (absent, mild, moderate, severe) by physicians blinded to clinical data. The estimated coronary calcium burden (ECCB) was computed as the sum of scores for each coronary artery (0 to 9 scale). A Revised Cardiac Risk Index was calculated for each patient. Perioperative MCE was defined as all-cause death or myocardial infarction within 30 days of surgery. RESULTS:<0.0001). An ECCB ≥3 was associated with 2-fold higher adjusted odds of MCE versus an ECCB <3 (adjusted odds ratio, 2.11 [95% CI, 1.42-3.12]). CONCLUSIONS:Prevalence and severity of coronary calcium obtained from existing nongated chest CT imaging improve preoperative clinical risk stratification before noncardiac surgery.
PMCID:10592001
PMID: 37732454
ISSN: 1524-4539
CID: 5599072

Major Adverse Cardiovascular Events After Colchicine Administration Before Percutaneous Coronary Intervention: Follow-Up of the Colchicine-PCI Trial

Shah, Binita; Smilowitz, Nathaniel R; Xia, Yuhe; Feit, Frederick; Katz, Stuart D; Zhong, Judy; Cronstein, Bruce; Lorin, Jeffrey D; Pillinger, Michael H
Periprocedural inflammation is associated with major adverse cardiovascular events in patients who undergo percutaneous coronary intervention (PCI). In the contemporary era, 5% to 10% of patients develop restenosis, and in the acute coronary syndrome cohort, there remains a 20% major adverse cardiovascular events rate at 3 years, half of which are culprit-lesion related. In patients at risk of restenosis, colchicine has been shown to reduce restenosis when started within 24 hours of PCI and continued for 6 months thereafter, compared with placebo. The Colchicine-PCI trial, which randomized patients to a 1-time loading dose of colchicine or placebo 1 to 2 hours before PCI, showed a dampening of the inflammatory response to PCI but no difference in postprocedural myocardial injury. On mean follow-up of 3.3 years, the incidence of major adverse cardiovascular events did not differ between colchicine and placebo groups (32.5% vs 34.9%; hazard ratio 0.95 [0.68 to 1.34]).
PMCID:10947505
PMID: 37536200
ISSN: 1879-1913
CID: 5728292