Initial Findings From the North American COVID-19 Myocardial Infarction Registry.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has impacted many aspects of ST-segment elevation myocardial infarction (STEMI) care, including timely access to primary percutaneous coronary intervention (PPCI). OBJECTIVES: The goal of the NACMI (North American COVID-19 and STEMI) registry is to describe demographic characteristics, management strategies, and outcomes of COVID-19 patients with STEMI. METHODS: A prospective, ongoing observational registry was created under the guidance of 3 cardiology societies. STEMI patients with confirmed COVID+ (group 1) or suspected (person under investigation [PUI]) (group 2) COVID-19 infection were included. A group of age- and sex-matched STEMI patients (matched to COVID+ patients in a 2:1 ratio) treated in the pre-COVID era (2015 to 2019) serves as the control group for comparison of treatment strategies and outcomes (group 3). The primary outcome was a composite of in-hospital death, stroke, recurrent myocardial infarction, or repeat unplanned revascularization. RESULTS: As of December 6, 2020, 1,185 patients were included in the NACMI registry (230 COVID+ patients, 495 PUIs, and 460 control patients). COVID+ patients were more likely to have minority ethnicity (Hispanic 23%, Black 24%) and had a higher prevalence of diabetes mellitus (46%) (all p < 0.001 relative to PUIs). COVID+ patients were more likely to present with cardiogenic shock (18%) but were less likely to receive invasive angiography (78%) (all p < 0.001 relative to control patients). Among COVID+ patients who received angiography, 71% received PPCI and 20% received medical therapy (both p < 0.001 relative to control patients). The primary outcome occurred in 36% of COVID+ patients, 13% of PUIs, and 5% of control patients (p < 0.001 relative to control patients). CONCLUSIONS: COVID+ patients with STEMI represent a high-risk group of patients with unique demographic and clinical characteristics. PPCI is feasible and remains the predominant reperfusion strategy, supporting current recommendations.

Mesenchymal stem cell mediates cardiac repair through autocrine, paracrine and endocrine axes.

In the past decade, despite key advances in therapeutic strategies following myocardial infarction, none can directly address the loss of cardiomyocytes following ischemic injury. Cardiac cell-based therapy is at the cornerstone of regenerative medicine that has shown potential for tissue repair. Mesenchymal stem cells (MSC) represent a strong candidate to heal the infarcted myocardium. While differentiation potential has been described as a possible avenue for MSC-based repair, their secreted mediators are responsible for the majority of the ascribed prohealing effects. MSC can either promote their own survival and proliferation through autocrine effect or secrete trophic factors that will act on adjacent cells through a paracrine effect. Prior studies have also documented beneficial effects even when MSCs were remotely delivered, much akin to an endocrine mechanism. This review aims to distinguish the paracrine activity of MSCs from an endocrine-like effect, where remotely transplanted cells can promote healing of the injured myocardium.

Everolimus-eluting bioresorbable vascular scaffold implantation to treat saphenous vein graft disease, single-center initial experience.

AIMS: Recent studies have shown favorable outcomes with everolimus-eluting bioresorbable vascular scaffold (BVS) in patients with stable coronary artery disease. Data on the use of BVS in saphenous vein graft disease (SVG) is currently lacking. METHODS AND RESULTS: A total of 10 consecutive patients (13 lesions, including 6 in-stent restenosis) who underwent BVS for SVG disease between May 2013 and June 2015 at a tertiary care institution were included. Median follow-up period was 874 (720-926) days. One patient had scaffold thrombosis (ScT) 15 months after implantation, which was treated medically. Another patient had target lesion revascularization (TLR) in two different lesions, where BVS was used to treat in-stent restenosis. The composite endpoint of TLR, ScT, target vessel myocardial infarction, and cardiac death, was reached in two patients CONCLUSIONS: This first real-world data on the use of the ABSORB™ BVS in patients with SVG disease shows that its implantation is technically feasible. The observed rate of target lesion revascularization was similar to those observed with drug-eluting stents in similar settings. Larger studies are required to better define the optimal use of BVS to treat SVG disease.

Epidemiology, Management Strategies, and Outcomes of Patients With Chronic Total Coronary Occlusion.

Factors influencing the management of patients with chronic total occlusion (CTO) are poorly described. We sought to analyze the clinical and angiographic variables influencing the decision-making process of patients with CTO. Consecutive patients with at least 1 coronary artery CTO were included and categorized as managed either by percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG), or medical therapy (MT). Patients with previous CABG were excluded. The CTO SYNTAX score (CTO-SS) was defined as the ratio between the score attributed to the CTO lesion in the SYNTAX score calculation and the total SYNTAX score. Independent predictors of management strategies were sought. A total of 510 patients were included (CTO incidence: 20%): 9% were treated with PCI, 34% with CABG, and 57% with MT. SYNTAX score was lowest in PCI (14.8 [11.0 to 18.5]) and highest in CABG (31.5 [25.0 to 38.8], p <0.0001). PCI was attempted more often in patients with higher CTO-SS (i.e., those with higher contribution to the overall SYNTAX score from the CTO lesion; 88% had a CTO-SS >0.5). Conversely, CABG was preferred in subjects with lower CTO-SS (61% had a CTO-SS ≤0.5, p <0.0001). Age, ejection fraction, SYNTAX score, and age of the CTO were independent predictors of revascularization. At mid-term follow-up, unsuccessful revascularization or MT was independently associated with death (hazard ratio 7.2, p = 0.0005). In conclusion, CTOs are frequently documented in clinical practice. However, less than a half is revascularized. Management strategies are influenced by angiographic variables such as the SYNTAX score and the newly proposed CTO-SS.

Contrast-Induced Nephropathy: From Pathophysiology to Preventive Strategies.

Contrast-induced nephropathy (CIN) is a frequent cause of acute kidney injury in hospitalized patients. CIN is most commonly defined as either an absolute (≥ 0.5 mg/dL; ≥ 44 µmol/L) or relative (≥ 25%) increase in serum creatinine levels at 48-72 hours after exposure to iodinated contrast media (CM). Its occurrence is associated with worsened clinical outcomes. Patients undergoing cardiac catheterization and percutaneous coronary intervention are particularly vulnerable to CIN. The complex pathophysiology of CIN involves different mechanisms, such as vasoconstriction, oxidative stress, medullary ischemia, and the direct toxic effects of CM. In CIN pathophysiology, both patient-related and procedure-related risk factors have been identified. The risk for CIN can be reliably estimated with clinical scores such as that proposed by Mehran. Because no definitive treatment exists for CIN, the most effective strategy remains prevention. Several interventions have been investigated--from hydration to various pharmacologic agents and mechanical devices. In this state-of-the-art article, we review the pathophysiology, diagnosis, risk stratification, and preventive strategies for CIN.

Laser atherectomy for balloon failure in chronic total occlusion. When the going gets tough.

Excimer laser coronary atherectomy (ELCA) is based on ultraviolet energy and is capable of disintegrating atheroma, without burning or grossly fragmenting it. ELCA has proven effective in the percutaneous treatment of a variety of complex lesions, including chronic total occlusions (CTO) and severely calcified lesions, in case of balloon failure-tocross or failure-to-expand. Here we present a case of a successful CTO recanalization with ELCA after balloon failure, review the literature on this topic, and present an algorithm outlining the management of this challenging clinical scenario.

Differential 1-year clinical outcomes for ST-segment elevation myocardial infarction related to stent thrombosis or saphenous vein graft thrombosis.

AIM: Thrombosis of stents and of saphenous vein grafts (SVG) remains a severe complication of either revascularization techniques that often are present as ST elevation myocardial infarction (STEMI). The aim of this longitudinal cohort study was to compare the 1-year clinical outcomes among STEMI patients requiring primary PCI due to stent thrombosis and graft occlusion presenting with STEMI. METHODS AND RESULTS: We prospectively collected data on all patients undergoing primary PCI at the Montreal Heart Institute between April 1, 2007 and March 30, 2008. Study patients were grouped according to the etiology of the STEMI: stent thrombosis, graft thrombosis, or atherosclerosis-related STEMIs (control group). The primary combined end-point, major adverse cardiac events (MACE), was defined as death, myocardial infarction, and target vessel revascularization within 12 months as primary end point. Of the 489 STEMI patients included in the study, 23 were due to stent thrombosis, 22 to graft thrombosis, and 444 in the control group. Stent and graft thromboses were associated with a higher MACE rates, 26.1 and 22.7%, respectively, compared to the control group, 9.3% (P = 0.004). Moreover, only stent thrombosis was associated with an increased risk of MACE (HR 2.57, confidence interval 95% 1.08-6.08. CONCLUSION: Patients with stent thrombosis present with higher rate of reinfarction while graft thrombosis is associated with an increase in 1-year cardiac mortality. Using multivariate analysis, higher MACE rates were associated with stent thrombosis as compared to graft thrombosis.

The bone marrow-cardiac axis: role of endothelial progenitor cells in heart failure.

Congestive heart failure (CHF) remains a leading cause of mortality in the developed world. The complex mechanisms involved in the pathophysiology of heart failure (HF) explain some of the limited impact of current recognised therapeutic strategies. There is, therefore, a definite need for new alternative molecular and biological pathways to address the treatment of this condition. Over the past decade, much research has focussed upon identifying the ideal cell type to promote myocardial regeneration. Recently, striking reports suggested the concept that bone-marrow (BM)-derived endothelial progenitor cells (EPCs) participate in cardiac regeneration and function recovery in the setting of progressive HF. The modulation of this complex interaction between the BM and the circulating EPCs could be at the crossroad of multiple therapeutic strategies aimed to protect or restore the myocardium in the setting of the CHF. However, there are uncertainties and unresolved issues regarding the mechanisms possibly responsible for the functional benefits observed in chronic experimental and pre-clinical studies. Hence, the BM-cardiac axis concept has created overwhelming enthusiasm and subsequent scepticism in the field of cardiac repair and regeneration. Further intensive research in basic science and clinical arenas are needed to elucidate the potential association between BM and heart function recovery, particularly in the progression towards advance stages of CHF. In this review, we focus on the importance of the BM-cardiac axis and BM-derived EPCs in the pathophysiology, clinical progression and potential treatment of CHF.

The paracrine effect: pivotal mechanism in cell-based cardiac repair.

Cardiac cell therapy has emerged as a controversial yet promising therapeutic strategy. Both experimental data and clinical applications in this field have shown modest but tangible benefits on cardiac structure and function and underscore that transplanted stem-progenitor cells can attenuate the postinfarct microenvironment. The paracrine factors secreted by these cells represent a pivotal mechanism underlying the benefits of cell-mediated cardiac repair. This article reviews key studies behind the paracrine effect related to the cardiac reparative effects of cardiac cell therapy.

In vivo myocardial distribution of multipotent progenitor cells following intracoronary delivery in a swine model of myocardial infarction.

AIMS: There are few data comparing the fate of multipotent progenitor cells (MPCs) used in cardiac cell therapy after myocardial infarction (MI). To document in vivo distribution of MPCs delivered by intracoronary (IC) injection. METHODS AND RESULTS: Using an anterior MI swine model, near-infrared (NIR) fluorescence was used for in vivo tracking of labelled MPCs [mesenchymal stromal (MSCs), bone marrow mononuclear (BMMNCs), and peripheral blood mononuclear (PBMNCs)] cells early after IC injection. Signal intensity ratios (SIRs) of injected over non-injected (reference) zones were used to report NIR fluorescence emission. Following IC injection, significant differences in mean SIR were documented when MSCs were compared with BMMNCs [1.28 +/- 0.10 vs. 0.77 +/- 0.11, P < 0.001; 95% CI (0.219, 0.805), respectively] or PBMNCs [1.28 +/- 0.10 vs. 0.80 +/- 0.14, P = 0.005; 95% CI (0.148, 0.813), respectively]. Differences were maintained during the 60 min tracking period, with only the MSC-injected groups continuously emitting NIR fluorescence (SIR>1). This is correlated with greater cell retention for MSCs relative to mononuclear cells. However, there was evidence of MSC-related vessel plugging in some swine. CONCLUSION: Our in vivo NIR fluorescence findings suggest that MPC distribution and retention immediately after intracoronary delivery vary depending on cell population and could potentially impact the clinical efficacy of cardiac cell therapy.

Reversal of cardiac dysfunction after long-term expression of SERCA2a by gene transfer in a pre-clinical model of heart failure.

OBJECTIVES: The aim of this study was to examine the effects of sarcoplasmic reticulum Ca(2+) ATPase (SERCA2a) gene transfer in a swine heart failure (HF) model. BACKGROUND: Reduced expression and activity of SERCA2a have been documented in HF. Prior studies have reported the beneficial effects of short-term SERCA2a overexpression in rodent models. However, the effects of long-term expression of SERCA2a in pre-clinical large animal models are not known. METHODS: Yorkshire-Landrace pigs were used (n = 16) to create volume overload by percutaneously severing chordae tendinae of the mitral apparatus with a bioptome to induce mitral regurgitation. At 2 months, pigs underwent intracoronary delivery of either recombinant adeno-associated virus type 1 (rAAV1) carrying SERCA2a under a cytomegalovirus promoter (rAAV1.SERCA2a) (n = 10; group 1) or saline (n = 6; group 2). RESULTS: At 2 months, study animals were found to be in a compensated state of volume-overload HF (increased left ventricular internal diastolic and systolic diameters [LVIDd and LVIDs]). At 4 months, gene transfer resulted in: 1) positive left ventricular (LV) inotropic effects (adjusted peak left ventricular pressure rate of rise (dP/dt)max/P, 21.2 +/- 3.2 s(-1) group 1 vs. 15.5 +/- 3.0 s(-1) group 2; p < 0.01); 2) improvement in LV remodeling (% change in LVIDs -3.0 +/- 10% vs. +15 +/- 11%, respectively; p < 0.01). At follow-up, brain natriuretic peptide levels remained stable in group 1 after gene transfer, in contrast to rising levels in group 2. Further, cardiac SERCA2a expression was significantly decreased in group 2 whereas in group 1 it was restored to normal levels. There was no histopathological evidence of acute myocardial inflammation or necrosis. CONCLUSIONS: Using a large-animal, volume-overload model of HF, we report that long-term overexpression of SERCA2a by in vivo rAAV1-mediated intracoronary gene transfer preserved systolic function, potentially prevented diastolic dysfunction, and improved ventricular remodeling.

In vivo tracking in cardiac stem cell-based therapy.

Cell-based therapy has been heralded as a promising, novel therapeutic strategy for cardiovascular diseases. Despite a rapid transition from animal studies to clinical trials, there remain numerous unresolved, and at times, controversial issues with respect to underlying molecular mechanisms. In parallel, recent advances in the field of molecular imaging has provided a means to bridge the gap in knowledge through in vivo stem cells tracking. Herein, we review current in vivo imaging techniques and future directions for tracking the effects of cell-based therapy.

Association of platelet counts on presentation and clinical outcomes in ST-elevation myocardial infarction (from the TIMI Trials).

Platelet activation and aggregation play pivotal roles in the thrombotic process of acute coronary syndromes. However, data regarding platelet count and its association with clinical outcomes in the setting of ST-elevation myocardial infarction (STEMI) are limited. We hypothesized that higher platelet counts on presentation would be associated with poorer clinical outcomes. Data from 10,793 patients with STEMI in the Thrombolysis In Myocardial Infarction (TIMI) trials database were analyzed. Mean platelet count on presentation was 254.8 x 10(3)/microl. Higher platelet counts were associated with higher rates of adverse clinical outcomes at 30 days. In a multivariable analysis that adjusted for confounders of platelet counts (age, gender, weight, diabetes, and smoking), higher platelet counts remained associated with an increased risk of the combined end point of death, reinfarction, and congestive heart failure. With a reference group of platelet counts <200 x 10(3)/microl, the multivariable odds ratios were 1.22 (95% confidence interval 1.05 to 1.42, p = 0.009) for platelet counts of 201 to 300 x 10(3)/microl, 1.37 (95% confidence interval 1.11 to 1.68, p = 0.002) for counts of 301 to 400 x 10(3)/microl, and 1.71 (95% confidence interval 1.16 to 2.51, p = 0.005) for counts >400 x 10(3)/microl. Further, a greater decrease in follow-up platelet counts (compared with baseline values) was independently associated with an increased risk of reinfarction at 30 days (odds ratio 1.44 for every decrease of 100 x 10(3)/microl unit of platelets, 95% confidence interval 1.13 to 1.82, p = 0.03). In conclusion, in STEMI, a higher platelet count on presentation was independently associated with adverse clinical outcomes, whereas a greater subsequent platelet count decrease was associated with an increased risk of reinfarction.

Sudden death and hypertrophic cardiomyopathy: a review.

Hypertrophic cardiomyopathy is a genetic disease that affects the cardiac sarcomere, resulting in myocardial hypertrophy and disarray. Affected patients have a predisposition for malignant ventricular tachyarrhythmias and, consequently, sudden cardiac death. With the availability of therapeutic measures that prevent sudden death, the identification of high-risk patients is now of greater importance. Clinical risk factors for sudden death (ie, age, syncope, family history of sudden cardiac death, cardiac arrest survivor, nonsustained ventricular tachycardia and abnormal blood pressure response to exercise) have been identified. The clinical electrophysiological study is of limited use for stratifying these patients. More recently, increased attention has been given to the degree of echocardiographically documented left ventricular hypertrophy and prognostically significant genetic mutations. Once a high-risk patient is identified, prophylactic treatment is warranted. For this purpose, amiodarone has been supplanted by the implantable cardioverter-defibrillator. Implantable cardioverter-defibrillator treatment appears to reduce the risk of sudden cardiac death in both primary and secondary prevention settings. Thus, tools are now available to identify and treat high-risk patients with hypertrophic cardiomyopathy.