Cardiac Catheterization Laboratory Management of the Comatose Adult Patient With an Out-of-Hospital Cardiac Arrest: A Scientific Statement From the American Heart Association.

Out-of-hospital cardiac arrest is a leading cause of death, accounting for ≈50% of all cardiovascular deaths. The prognosis of such individuals is poor, with <10% surviving to hospital discharge. Survival with a favorable neurologic outcome is highest among individuals who present with a witnessed shockable rhythm, received bystander cardiopulmonary resuscitation, achieve return of spontaneous circulation within 15 minutes of arrest, and have evidence of ST-segment elevation on initial ECG after return of spontaneous circulation. The cardiac catheterization laboratory plays an important role in the coordinated Chain of Survival for patients with out-of-hospital cardiac arrest. The catheterization laboratory can be used to provide diagnostic, therapeutic, and resuscitative support after sudden cardiac arrest from many different cardiac causes, but it has a unique importance in the treatment of cardiac arrest resulting from underlying coronary artery disease. Over the past few years, numerous trials have clarified the role of the cardiac catheterization laboratory in the management of resuscitated patients or those with ongoing cardiac arrest. This scientific statement provides an update on the contemporary approach to managing resuscitated patients or those with ongoing cardiac arrest.

Ticagrelor or prasugrel versus clopidogrel in patients undergoing percutaneous coronary intervention for chronic coronary syndromes.

BACKGROUND: Potent P2Y12 inhibitors such as ticagrelor and prasugrel are superior to clopidogrel in acute coronary syndrome (ACS) patients treated with percutaneous coronary intervention (PCI). Whether this benefit extends to a patient population with chronic coronary syndromes (CCS) is unclear. AIMS: We sought to compare the safety and efficacy of prasugrel and ticagrelor versus clopidogrel in patients undergoing PCI for CCS. METHODS: Consecutive patients undergoing PCI for CCS at a tertiary centre between 2014 and 2019 who were discharged on prasugrel or ticagrelor were compared with those on clopidogrel. The primary endpoint was the composite of death and myocardial infarction (MI), with secondary outcomes including rates of bleeding, stroke, and target vessel revascularisation at 1 year. RESULTS: Overall, 11,508 patients were included in the study (ticagrelor/prasugrel n=2,860 [24.9%], clopidogrel n=8,648 [75.1%]) with an increasing frequency of potent P2Y12 inhibitor use over the study period (ptrend<0.001). Clopidogrel was used more frequently in patients with multimorbid risk factors, whereas anatomical or procedural complexity was associated with ticagrelor/prasugrel use (left main PCI, bifurcation PCI, number of lesions, rotational atherectomy). No difference in the incidence of death or MI was noted across the groups (ticagrelor/prasugrel vs clopidogrel: 2.7% vs 3.1%, adjusted hazard ratio [adjHR] 0.86, 95% confidence interval [CI]: 0.62-1.17; p=0.33) or secondary outcomes including bleeding (adjHR 0.75, 95% CI: 0.46-1.21; p=0.23) on propensity score stratification analysis. Additionally, no difference in the primary outcome was observed across subgroups, including those undergoing complex PCI. CONCLUSIONS: Ticagrelor and prasugrel are increasingly used in patients with CCS undergoing PCI with similar 1-year efficacy and safety when compared to clopidogrel. Whether use of these agents can be beneficial in patients undergoing PCI for CCS with a high thrombotic and low bleeding risk warrants further study.

Temporary mechanical circulatory support devices: practical considerations for all stakeholders.

Originally intended for life-saving salvage therapy, the use of temporary mechanical circulatory support (MCS) devices has become increasingly widespread in a variety of clinical settings in the contemporary era. Their use as a short-term, prophylactic support vehicle has expanded to include procedures in the catheterization laboratory, electrophysiology suite, operating room and intensive care unit. Accordingly, MCS device design and technology continue to develop at a rapid pace. In this Review, we describe the functionality, indications, management and complications associated with temporary MCS, together with scenario-specific utilization, goal-directed development and bioengineering of future devices. We address various considerations for the use of temporary MCS devices in both prophylactic and rescue scenarios, with input from stakeholders from various cardiovascular specialties, including interventional and heart failure cardiology, electrophysiology, cardiothoracic anaesthesiology, critical care and cardiac surgery.

Ticagrelor vs Prasugrel in a Contemporary Real-World Cohort Undergoing Percutaneous Coronary Intervention.

BACKGROUND: Potent P2Y12 agents such as ticagrelor and prasugrel are increasingly utilized across the clinical spectrum of patients undergoing percutaneous coronary intervention (PCI). There is a paucity of data supporting their use in a patient population inclusive of both acute coronary syndrome (ACS) and chronic coronary syndrome (CCS) patients. OBJECTIVES: The authors compared the efficacy and safety of ticagrelor and prasugrel in a real-world contemporary PCI cohort. METHODS: Consecutive patients undergoing PCI between 2014 and 2019 discharged on either prasugrel or ticagrelor were included from the prospectively collected institutional PCI registry. Primary endpoint was the composite of death and myocardial infarction (MI), with secondary outcomes including rates of bleeding, stroke, and target vessel revascularization at 1 year. RESULTS: Overall, 3,858 patients were included in the study (ticagrelor: n = 2,771; prasugrel: n = 1,087), and a majority (48.4%) underwent PCI in the context of CCS. Patients prescribed ticagrelor were more likely to be female, have a history of cerebrovascular disease, and have ACS presentation, while those receiving prasugrel were more likely to be White with a higher prevalence of prior revascularization. No difference in the risk of death or MI was noted across the groups (ticagrelor vs prasugrel: 3.3% vs 3.1%; HR: 0.88; 95% CI: 0.54-1.43; P = 0.59). Rates of target vessel revascularization were significantly lower in the ticagrelor cohort (9.3% vs 14.0%; adjusted HR: 0.71; 95% CI: 0.55-0.91; P = 0.007) with no differences in stroke or bleeding. The results were consistent in patients with CCS (HR: 0.84; 95% CI: 0.46-1.54) and ACS (HR: 1.18; 95% CI: 0.46-1.54), without evidence of interaction (P = 0.37), and confirmed across multivariable adjustment and propensity score stratification analysis. CONCLUSIONS: In this contemporary patient population undergoing PCI, prasugrel and ticagrelor were associated with similar 1-year efficacy and safety.

Predictors of Left Ventricular Ejection Fraction Improvement After Primary Stenting in ST-Segment Elevation Myocardial Infarction (from the Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction Trial).

The predictors of improvement in left ventricular ejection fraction (LVEF) after primary percutaneous coronary intervention (PCI) in ST-segment elevation myocardial infarction (STEMI) are poorly understood. We sought to determine the prevalence and clinical and angiographic predictors of LVEF improvement after primary PCI in STEMI. In the Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction trial, 3,602 patients presenting with STEMI were randomized to heparin + a glycoprotein IIb/IIIa inhibitor versus bivalirudin. Routine 13-month angiographic follow-up was performed in a prespecified substudy of 656 stented patients. The median [25%, 75%] change in LVEF from baseline to 13 months was +2.4% [-5.9%, 11.8%]; LVEF increased or remained unchanged in 379 patients (57.8%; median Δ +9.8% [4.3%, 16.4%]) and fell in 277 patients (42.2%; median Δ -7.0% [-11.8%, -3.6%]). Independent predictors of LVEF improvement were female gender (p = 0.002), lower baseline LVEF (p <0.0001), Thrombolysis in Myocardial Infarction 3 flow after PCI (p = 0.03), shorter lesion length (p = 0.04), and lower post-PCI peak MB isoenzyme of creatine kinase (p <0.0001). In conclusion, in the Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction trial, although LVEF improved during follow-up after primary PCI in more than half of patients, left ventricular function worsened over time in a substantial proportion, the occurrence of which may be predicted by clinical, angiographic, and laboratory variables.

Incidence, predictors, and implications of reinfarction after primary percutaneous coronary intervention in ST-segment-elevation myocardial infarction: the Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction Trial.

BACKGROUND: Reinfarction after primary percutaneous coronary intervention in patients with ST-segment-elevation myocardial infarction has negative consequences. Little is known about reinfarction after drug-eluting stents and bivalirudin anticoagulation. We, therefore, sought to determine the incidence, predictors, and implications of reinfarction after primary percutaneous coronary intervention in the contemporary era. METHODS AND RESULTS: Outcomes were assessed in 3202 patients undergoing stent implantation for ST-segment-elevation myocardial infarction in the Harmonizing Outcomes with RevascularIZatiON and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trial. Independent predictors of reinfarction and mortality were identified by Cox proportional hazards modeling. The cumulative incidence of reinfarction was 1.8% at 30 days, 4.0% at 1 year, and 6.9% at 3 years. Definite stent thrombosis was responsible for 76.3% of reinfarctions occurring within 30 days and 52.0% of all reinfarctions within 3 years. Independent predictors of reinfarction were current smoking, Killip class ≥2, baseline thrombocytosis, multivessel disease, symptom onset-to-balloon time, and total stent length. Randomization to bivalirudin versus heparin plus a glycoprotein IIb/IIIa inhibitor and use of drug-eluting versus bare metal stents were not significant predictors of reinfarction. Reinfarction was a powerful independent predictor of subsequent cardiac mortality (hazard ratio [95% confidence interval]=7.65 [4.47-13.09]; P<0.0001) and all-cause mortality (hazard ratio [95% confidence interval]=2.88 [1.74-4.78]; P<0.0001). CONCLUSIONS: Despite advances in pharmacotherapy and stents, reinfarction after primary percutaneous coronary intervention is not infrequent, in the contemporary era is most often attributable to stent thrombosis, and is strongly associated with subsequent cardiac and all-cause mortality. Further enhancements in drugs and devices to prevent reinfarction are needed to improve outcomes in high-risk patients with ST-segment-elevation myocardial infarction. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00433966.

Advancing functional engineered cardiac tissues toward a preclinical model of human myocardium.

Cardiac experimental biology and translational research would benefit from an in vitro surrogate for human heart muscle. This study investigated structural and functional properties and interventional responses of human engineered cardiac tissues (hECTs) compared to human myocardium. Human embryonic stem cell-derived cardiomyocytes (hESC-CMs, >90% troponin-positive) were mixed with collagen and cultured on force-sensing elastomer devices. hECTs resembled trabecular muscle and beat spontaneously (1.18 ± 0.48 Hz). Microstructural features and mRNA expression of cardiac-specific genes (α-MHC, SERCA2a, and ACTC1) were comparable to human myocardium. Optical mapping revealed cardiac refractoriness with loss of 1:1 capture above 3 Hz, and cycle length dependence of the action potential duration, recapitulating key features of cardiac electrophysiology. hECTs reconstituted the Frank-Starling mechanism, generating an average maximum twitch stress of 660 µN/mm(2) at Lmax, approaching values in newborn human myocardium. Dose-response curves followed exponential pharmacodynamics models for calcium chloride (EC50 1.8 mM) and verapamil (IC50 0.61 µM); isoproterenol elicited a positive chronotropic but negligible inotropic response, suggesting sarcoplasmic reticulum immaturity. hECTs were amenable to gene transfer, demonstrated by successful transduction with Ad.GFP. Such 3-D hECTs recapitulate an early developmental stage of human myocardium and promise to offer an alternative preclinical model for cardiology research.

Low-density lipoprotein levels in patients with acute heart failure.

Statins do not appear to have a significant benefit in heart failure (HF) as they do in coronary artery disease (CAD). Significant evidence exists that low serum cholesterol levels may be harmful in HF. This study sought to determine the optimal low-density lipoprotein (LDL) level in patients hospitalized with acute HF. Patients were included if they presented to the hospital with acute HF and had a lipid panel drawn during admission. The primary outcome was all-cause mortality, and secondary outcomes were rates of major cardiovascular (CV) events, left ventricular assist device (LVAD) implantation, and orthotopic heart transplantation (OHT). A total of 2428 patients were followed for a mean of 2.9±2.2 years. For the entire cohort, when compared with those with LDL levels >130 mg/dL, all-cause mortality was higher in those with LDL levels <71 mg/dL (hazard ratio, 1.68; 95% confidence interval, 1.31-2.167; P<.01). Results were similar when analyzing patients with LVEF ≤40%, HF of ischemic etiology only, and in statin users. The rates of CV events, LVAD implantation, or OHT in any comparison did not differ. Low LDL levels (<71 mg/dL), similar to low total cholesterol levels, were associated with a poorer prognosis and higher overall mortality in patients with HF, regardless of etiology and systolic function.

Myocyte-depleted engineered cardiac tissues support therapeutic potential of mesenchymal stem cells.

The therapeutic potential of mesenchymal stem cells (MSCs) for restoring cardiac function after cardiomyocyte loss remains controversial. Engineered cardiac tissues (ECTs) offer a simplified three-dimensional in vitro model system to evaluate stem cell therapies. We hypothesized that contractile properties of dysfunctional ECTs would be enhanced by MSC treatment. ECTs were created from neonatal rat cardiomyocytes with and without bone marrow-derived adult rat MSCs in a type-I collagen and Matrigel scaffold using custom elastomer molds with integrated cantilever force sensors. Three experimental groups included the following: (1) baseline condition ECT consisting only of myocytes, (2) 50% myocyte-depleted ECT, modeling a dysfunctional state, and (3) 50% myocyte-depleted ECT plus 10% MSC, modeling dysfunctional myocardium with intervention. Developed stress (DS) and pacing threshold voltage (VT) were measured using 2-Hz field stimulation at 37°C on culture days 5, 10, 15, and 20. By day 5, DS of myocyte-depleted ECTs was significantly lower than baseline, and VT was elevated. In MSC-supplemented ECTs, DS and VT were significantly better than myocyte-depleted values, approaching baseline ECTs. Findings were similar through culture day 15, but lost significance at day 20. Trends in DS were partly explained by changes in the cell number and alignment with time. Thus, supplementing myocyte-depleted ECTs with MSCs transiently improved contractile function and compensated for a 50% loss of cardiomyocytes, mimicking recent animal studies and clinical trials and supporting the potential of MSCs for myocardial therapy.

Outcome of elective endovascular abdominal aortic aneurysm repair in nonagenarians.

OBJECTIVE: Compared with open repair of abdominal aortic aneurysms (AAA), endovascular repair (EVAR) is associated with decreased perioperative morbidity and mortality in a standard patient population. This study sought to determine if the advantage of EVAR extends to patients aged ≥90 years. METHODS: This was a retrospective review from a prospectively maintained computerized database. Of the 322 patients aged ≥80 treated with EVAR from January 1997 to November 2007, 24 (1.9%) were aged ≥90. Mean age was 91.5 ± 1.5 years (range, 90-95 years), and 83.3% were men. Mean aneurysm size was 6.8 cm (range, 5.2-8.7 cm). RESULTS: Mean procedural blood loss was 490 mL (range, 100-4150 mL), and 20.8% required an intraoperative transfusion. Mean postoperative length of stay was 6.0 days, (median, 4 days; mode, 1 day; range, 1-42 days), with 33.3% of patients discharged on the first postoperative day. Amongst the 24 patients, there were 6 (25.0%) perioperative major adverse events, and 2 patients died, for a perioperative mortality rate of 8.3%. Mean follow-up was 20.5 months (range, 1-49 months). Overall, three patients (12.5%) required a secondary intervention, comprising thrombectomy, angioplasty, and proximal cuff extension. No patients required conversion to open repair. Two patients (8.3%) died of AAA rupture at 507 and 1254 days. Freedom from all-cause mortality was 83.3% at 1 year and 19.3% at 5 years. Freedom from aneurysm-related mortality was 87.5% at 1 year and 73.2% at 5 years. Endoleak occurred in five patients (20.8%), with three type I and two of indeterminate type; of these, two patients with type I endoleak underwent secondary intervention at 153 and 489 days after EVAR, of which one case was successful. CONCLUSION: Our study supports that EVAR in nonagenarians is associated with acceptable procedural success and perioperative morbidity and mortality. The medium-term results suggest that EVAR may be of limited benefit in very carefully selected patients who are aged ≥90 years.