Influence of Culprit Lesion Intervention on Outcomes in Infarct-Related Cardiogenic Shock With Cardiac Arrest.

BACKGROUND: Cardiac arrest (CA) is common in patients with infarct-related cardiogenic shock (CS). OBJECTIVES: The goal of this study was to identify the characteristics and outcomes of culprit lesion percutaneous coronary intervention (PCI) of patients with infarct-related CS stratified according to CA in the CULPRIT-SHOCK (Culprit Lesion Only PCI Versus Multivessel PCI in Cardiogenic Shock) randomized trial and registry. METHODS: Patients with CS with and without CA from the CULPRIT-SHOCK study were analyzed. All-cause death or severe renal failure leading to renal replacement therapy within 30 days and 1-year death were assessed. RESULTS: Among 1,015 patients, 550 (54.2%) had CA. Patients with CA were younger, more frequently male, had lower rates of peripheral artery disease, a glomerular filtration rate <30 mL/min, and left main disease, and they presented more often with clinical signs of impaired organ perfusion. The composite of all-cause death or severe renal failure within 30 days occurred in 51.2% of patients with CA vs 48.5% in non-CA patients (P = 0.39) and 1-year death in 53.8% vs 50.4% (P = 0.29), respectively. In a multivariate analysis, CA was an independent predictor of 1-year mortality (HR: 1.27; 95% CI: 1.01-1.59). In the randomized trial, culprit lesion-only PCI was superior to immediate multivessel PCI in patients both with and without CA (P for interaction = 0.6). CONCLUSIONS: More than 50% of patients with infarct-related CS had CA. These patients with CA were younger and had fewer comorbidities, but CA was an independent predictor of 1-year mortality. Culprit lesion-only PCI is the preferred strategy, both in patients with and without CA. (Culprit Lesion Only PCI Versus Multivessel PCI in Cardiogenic Shock [CULPRIT-SHOCK]; NCT01927549).

Impact of moderate or severe left ventricular outflow tract calcification on clinical outcomes of patients with severe aortic stenosis undergoing transcatheter aortic valve implantation with self- and balloon-expandable valves: a post hoc analysis from the SOLVE-TAVI trial.

BACKGROUND: Left ventricular outflow tract (LVOT) calcification has been associated with worse outcomes in patients undergoing transcatheter aortic valve implantation (TAVI) and may influence the selection of prosthetic valve type. AIMS: We aimed to evaluate the impact of LVOT calcification on outcomes after TAVI with a self-expanding valve (SEV) versus a balloon-expandable valve (BEV). METHODS: Patients of the SOLVE-TAVI trial, randomised to Edwards SAPIEN 3 or Medtronic Evolut R, were divided according to LVOT calcification into no/mild (≤1 calcium nodule extending <5 mm and covering <10% of the LVOT perimeter) and moderate/severe LVOT calcification groups. The primary endpoint was a composite of death, stroke, moderate/severe paravalvular regurgitation, permanent pacemaker implantation and annulus rupture at 30 days. Additional endpoints included all-cause and cardiovascular mortality at 1 year. RESULTS: Out of 416 eligible patients, moderate/severe LVOT calcification was present in 143 (34.4%). Moderate/severe LVOT calcification was associated with significantly longer fluoroscopy time and higher rates of pre- and post-dilation. Regardless of the LVOT calcification group, there was no significant difference in the primary endpoint associated with the valve type (no/mild LVOT calcification group: SEV 25.0% vs BEV 27.0%; hazard ratio [HR] 1.10, 95% confidence interval [95% CI]: 0.68-1.73; p=0.73 and moderate/severe LVOT calcification group: SEV 25.0% vs BEV 19.4%; HR 0.76, 95% CI: 0.38-1.61; p=0.49), no significant interaction between LVOT calcification and valve type (pint=0.29) and no differences between SEV vs BEV within LVOT calcification groups regarding 1-year all-cause and cardiovascular mortality. CONCLUSIONS: Moderate/severe LVOT calcification was associated with longer fluoroscopy time and an increased need for pre- and post-dilation, but not with a higher incidence of early and mid-term adverse clinical outcomes, regardless of valve type. (ClinicalTrials.gov: NCT02737150).

Prognostic relevance of peri-infarct zone measured by cardiovascular magnetic resonance in patients with ST-segment elevation myocardial infarction.

BACKGROUND: Cardiac magnetic resonance (CMR) imaging provides valuable prognostic information in patients with ST-elevation myocardial infarction (STEMI). The peri-infarct zone (PIZ) is a potential marker for post-infarction risk stratification. The aim of this study was to assess the prognostic impact of PIZ in a large multicenter STEMI-trial. METHODS: The study population consisted of 704 consecutive patients undergoing CMR within 10 days after STEMI to assess established parameters of myocardial injury and additionally the extent of PIZ. The primary clinical endpoint was major adverse cardiac events (MACE) consisting of death, re-infarction and new congestive heart failure within 1 year after infarction. RESULTS: The median heterogeneous PIZ-volume in the overall population was 14 ml (interquartile range [IQR] 7 to 24 ml). Male sex, infarct size, and left ventricular ejection fraction were identified as independent predictors of larger PIZ alterations. Patients with MACE had a significantly larger PIZ volume compared to patients without adverse events (21 ml [IQR 12 to 35 ml] versus 14 ml [IQR 7 to 23 ml]; p = 0.001). In stepwise multivariable Cox regression analysis, PIZ > median (>14 ml) emerged as an independent predictor of MACE (hazard ratio [HR] 2.84; 95% confidence interval [CI] 1.34 to 6.00; p = 0.006) in addition to the Thrombolysis In Myocardial Infarction (TIMI) risk score (HR 1.53; 95% CI 1.19 to 1.53; p < 0.001). Addition of PIZ to a CMR risk model comprising LVEF, infarct size and microvascular obstruction resulted in net reclassification improvement of 0.46 (0.19-0.73, p < 0.001). CONCLUSION: In this currently largest prospective, multicenter CMR study assessing PIZ, the extent of PIZ emerged as an independent predictor of MACE and a potential novel marker for optimized risk stratification in STEMI patients. ClinicalTrials.gov: NCT00712101.

The novel cystatin C, lactate, interleukin-6, and N-terminal pro-B-type natriuretic peptide (CLIP)-based mortality risk score in cardiogenic shock after acute myocardial infarction.

BACKGROUND: Cardiogenic shock (CS) complicating acute myocardial infarction (AMI) still reaches excessively high mortality rates. This analysis is aimed to develop a new easily applicable biomarker-based risk score. METHODS AND RESULTS: A biomarker-based risk score for 30-day mortality was developed from 458 patients with CS complicating AMI included in the randomized CULPRIT-SHOCK trial. The selection of relevant predictors and the coefficient estimation for the prognostic model were performed by a penalized multivariate logistic regression analysis. Validation was performed internally, internally externally as well as externally in 163 patients with CS included in the randomized IABP-SHOCK II trial. Blood samples were obtained at randomization. The two trials are registered with ClinicalTrials.gov (NCT01927549 and NCT00491036), are closed to new participants, and follow-up is completed. Out of 58 candidate variables, the four strongest predictors for 30-day mortality were included in the CLIP score (cystatin C, lactate, interleukin-6, and N-terminal pro-B-type natriuretic peptide). The score was well calibrated and yielded high c-statistics of 0.82 [95% confidence interval (CI) 0.78-0.86] in internal validation, 0.82 (95% CI 0.75-0.89) in internal-external (temporal) validation, and 0.73 (95% CI 0.65-0.81) in external validation. Notably, it outperformed the Simplified Acute Physiology Score II and IABP-SHOCK II risk score in prognostication (0.83 vs 0.62; P < 0.001 and 0.83 vs. 0.76; P = 0.03, respectively). CONCLUSIONS: A biomarker-only score for 30-day mortality risk stratification in infarct-related CS was developed, extensively validated and calibrated in a prospective cohort of contemporary patients with CS after AMI. The CLIP score outperformed other clinical scores and may be useful as an early decision tool in CS.

Extracorporeal life support in patients with acute myocardial infarction complicated by cardiogenic shock - Design and rationale of the ECLS-SHOCK trial.

BACKGROUND: In acute myocardial infarction complicated by cardiogenic shock the use of mechanical circulatory support devices remains controversial and data from randomized clinical trials are very limited. Extracorporeal life support (ECLS) - venoarterial extracorporeal membrane oxygenation - provides the strongest hemodynamic support in addition to oxygenation. However, despite increasing use it has not yet been properly investigated in randomized trials. Therefore, a prospective randomized adequately powered clinical trial is warranted. STUDY DESIGN: The ECLS-SHOCK trial is a 420-patient controlled, international, multicenter, randomized, open-label trial. It is designed to compare whether treatment with ECLS in addition to early revascularization with percutaneous coronary intervention or alternatively coronary artery bypass grafting and optimal medical treatment is beneficial in comparison to no-ECLS in patients with severe infarct-related cardiogenic shock. Patients will be randomized in a 1:1 fashion to one of the two treatment arms. The primary efficacy endpoint of ECLS-SHOCK is 30-day mortality. Secondary outcome measures such as hemodynamic, laboratory, and clinical parameters will serve as surrogate endpoints for prognosis. Furthermore, a longer follow-up at 6 and 12 months will be performed including quality of life assessment. Safety endpoints include peripheral ischemic vascular complications, bleeding and stroke. CONCLUSIONS: The ECLS-SHOCK trial will address essential questions of efficacy and safety of ECLS in addition to early revascularization in acute myocardial infarction complicated by cardiogenic shock.

Prognostic Value of SYNTAX Score in Patients With Infarct-Related Cardiogenic Shock: Insights From the CULPRIT-SHOCK Trial.

OBJECTIVES: This study sought to evaluate the prognostic value of the SYNTAX (SYNergy between PCI with TAXUS and Cardiac Surgery) scores in patients undergoing percutaneous coronary intervention (PCI) for multivessel coronary disease with infarct-related cardiogenic shock (CS). BACKGROUND: The prognostic value of the SYNTAX score in this high-risk setting remains unclear. METHODS: The CULPRIT-SHOCK (Culprit Lesion Only PCI versus Multivessel PCI in Cardiogenic Shock) trial was an international, open-label trial, where patients presenting with infarct-related CS and multivessel disease were randomized to a culprit-lesion-only or an immediate multivessel PCI strategy. Baseline SYNTAX score was assessed by a central core laboratory and categorized as low SYNTAX score (SS ≤22), intermediate SYNTAX score (2232). Adjudicated endpoints of interest were the 30-day risk of death or renal replacement therapy (RRT) and 1-year death. Associations between baseline SYNTAX score and outcomes were assessed using multivariate logistic regression. RESULTS: Pre-PCI SYNTAX score was available in 624 patients, of whom 263 (42.1%), 207 (33.2%) and 154 (24.7%) presented with low, intermediate and high SYNTAX score, respectively. A stepwise increase in the incidence of adverse events was observed from low to intermediate and high SYNTAX score for the 30-day risk of death or RRT and the 1-year risk of death (p < 0.001, for all). After multiple adjustments, intermediate and high SYNTAX score remained strongly associated with 30-day risk of death or renal replacement therapy and 1-year risk of all-cause death. There was no significant interaction between SYNTAX score and the coronary revascularization strategy for any outcomes. CONCLUSIONS: In patients presenting with multivessel disease and infarct-related CS, the SYNTAX score was strongly associated with 30-day death or RRT and 1-year mortality.

Sex-Specific Management in Patients With Acute Myocardial Infarction and Cardiogenic Shock: A Substudy of the CULPRIT-SHOCK Trial.

BACKGROUND: Women are more likely to suffer and die from cardiogenic shock (CS) as the most severe complication of acute myocardial infarction. Data concerning optimal management for women with CS are scarce. Aim of this study was to better define characteristics of women experiencing CS and to the influence of sex on different treatment strategies. METHODS: In the CULPRIT-SHOCK trial (The Culprit Lesion Only PCI Versus Multivessel PCI in Cardiogenic Shock), patients with CS complicating acute myocardial infarction and multivessel coronary artery disease were randomly assigned to one of the following revascularization strategies: either percutaneous coronary intervention of the culprit-lesion-only or immediate multivessel percutaneous coronary intervention. Primary end point was composite of death from any cause or severe renal failure leading to renal replacement therapy within 30 days. We investigated sex-specific differences in general and according to the revascularization strategies. RESULTS: Among all 686 randomized patients included in the analysis, 24% were women. Women were older and had more often diabetes mellitus and renal insufficiency, whereas they had less often history of previous acute myocardial infarction and smoking. After 30 days, the primary clinical end point was not significantly different between groups (56% women versus 49% men; odds ratio, 1.29 [95% CI, 0.91-1.84]; P=0.15). There was no interaction between sex and coronary revascularization strategy regarding mortality and renal failure (Pinteraction=0.11). The primary end point occurred in 56% of women treated by the culprit-lesion-only strategy versus 42% men, whereas 55% of women and 55% of men in the multivessel percutaneous coronary intervention group. CONCLUSIONS: Although women presented with a different risk profile, mortality and renal replacement were similar to men. Sex did not influence mortality and renal failure according to the different coronary revascularization strategies. Based on these data, women and men presenting with CS complicating acute myocardial infarction and multivessel coronary artery disease should not be treated differently. However, further randomized trials powered to address potential sex-specific differences in CS are still necessary. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01927549.

Antithrombotic Therapy in Patients With Atrial Fibrillation and Acute Coronary Syndrome Treated Medically or With Percutaneous Coronary Intervention or Undergoing Elective Percutaneous Coronary Intervention: Insights From the AUGUSTUS Trial.

BACKGROUND: The safety and efficacy of antithrombotic regimens may differ between patients with atrial fibrillation who have acute coronary syndromes (ACS), treated medically or with percutaneous coronary intervention (PCI), and those undergoing elective PCI. METHODS: Using a 2×2 factorial design, we compared apixaban with vitamin K antagonists and aspirin with placebo in patients with atrial fibrillation who had ACS or were undergoing PCI and were receiving a P2Y12 inhibitor. We explored bleeding, death and hospitalization, as well as death and ischemic events, by antithrombotic strategy in 3 prespecified subgroups: patients with ACS treated medically, patients with ACS treated with PCI, and those undergoing elective PCI. RESULTS: Of 4614 patients enrolled, 1097 (23.9%) had ACS treated medically, 1714 (37.3%) had ACS treated with PCI, and 1784 (38.8%) had elective PCI. Apixaban compared with vitamin K antagonist reduced International Society on Thrombosis and Haemostasis major or clinically relevant nonmajor bleeding in patients with ACS treated medically (hazard ratio [HR], 0.44 [95% CI, 0.28-0.68]), patients with ACS treated with PCI (HR, 0.68 [95% CI, 0.52-0.89]), and patients undergoing elective PCI (HR, 0.82 [95% CI, 0.64-1.04]; Pinteraction=0.052) and reduced death or hospitalization in the ACS treated medically (HR, 0.71 [95% CI, 0.54-0.92]), ACS treated with PCI (HR, 0.88 [95% CI, 0.74-1.06]), and elective PCI (HR, 0.87 [95% CI, 0.72-1.04]; Pinteraction=0.345) groups. Compared with vitamin K antagonists, apixaban resulted in a similar effect on death and ischemic events in the ACS treated medically, ACS treated with PCI, and elective PCI groups (Pinteraction=0.356). Aspirin had a higher rate of bleeding than did placebo in patients with ACS treated medically (HR, 1.49 [95% CI, 0.98-2.26]), those with ACS treated with PCI (HR, 2.02 [95% CI, 1.53-2.67]), and those undergoing elective PCI (HR, 1.91 [95% CI, 1.48-2.47]; Pinteraction=0.479). For the same comparison, there was no difference in outcomes among the 3 groups for the composite of death or hospitalization (Pinteraction=0.787) and death and ischemic events (Pinteraction=0.710). CONCLUSIONS: An antithrombotic regimen consisting of apixaban and a P2Y12 inhibitor without aspirin provides superior safety and similar efficacy in patients with atrial fibrillation who have ACS, whether managed medically or with PCI, and those undergoing elective PCI compared with regimens that include vitamin K antagonists, aspirin, or both. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02415400.

Cardiac MRI and Texture Analysis of Myocardial T1 and T2 Maps in Myocarditis with Acute versus Chronic Symptoms of Heart Failure.

BackgroundThe establishment of a timely and correct diagnosis in heart failure-like myocarditis remains one of the most challenging in clinical cardiology.PurposeTo assess the diagnostic potential of texture analysis in heart failure-like myocarditis with comparison to endomyocardial biopsy (EMB) as the reference standard.Materials and MethodsSeventy-one study participants from the Magnetic Resonance Imaging in Myocarditis (MyoRacer) trial (ClinicalTrials.gov registration no. NCT02177630) with clinical suspicion for myocarditis and symptoms of heart failure were prospectively included (from August 2012 to May 2015) in the study. Participants underwent biventricular EMB and cardiac MRI at 1.5 T, including native T1 and T2 mapping and standard Lake Louise criteria. Texture analysis was applied on T1 and T2 maps by using an open-source software. Stepwise dimension reduction was performed for selecting features enabling the diagnosis of myocarditis. Diagnostic performance was assessed from the area under the curve (AUC) from receiver operating characteristic analyses with 10-fold cross validation.ResultsIn participants with acute heart failure-like myocarditis (n = 31; mean age, 47 years ± 17; 10 women), the texture feature GrayLevelNonUniformity from T2 maps (T2_GLNU) showed diagnostic performance similar to that of mean myocardial T2 time (AUC, 0.69 for both). The combination of mean T2 time and T2_GLNU had the highest AUC (0.76; 95% confidence interval [CI]: 0.43, 0.95), with sensitivity of 81% (25 of 31) and specificity of 71% (22 of 31). In patients with chronic heart failure-like myocarditis (n = 40; mean age, 48 years ± 13; 12 women), the histogram feature T2_kurtosis demonstrated superior diagnostic performance compared to that of all other single parameters (AUC, 0.81; 95% CI: 0.66, 0.96). The combination of the two texture features, T2_kurtosis and the GrayLevelNonUniformity from T1, had the highest diagnostic performance (AUC, 0.85; 95% CI: 0.57, 0.90; sensitivity, 90% [36 of 40]; and specificity, 72% [29 of 40]).ConclusionIn this proof-of-concept study, texture analysis applied on cardiac MRI T1 and T2 mapping delivers quantitative imaging parameters for the diagnosis of acute or chronic heart failure-like myocarditis and might be superior to Lake Louise criteria or averaged myocardial T1 or T2 values.© RSNA, 2019Online supplemental material is available for this article.See also the editorial by de Roos in this issue.

Cangrelor in cardiogenic shock and after cardiopulmonary resuscitation: A global, multicenter, matched pair analysis with oral P2Y12 inhibition from the IABP-SHOCK II trial.

AIMS: Cangrelor has a potentially favorable pharmacodynamic profile in cardiogenic shock (CS). We aimed to evaluate the clinical course of CS patients undergoing percutaneous coronary intervention (PCI) treated with cangrelor. METHODS AND RESULTS: We retrospectively identified 136 CS patients treated with cangrelor. Patients were 1:1 matched to CS patients from the IABP-SHOCK II trial not receiving cangrelor by age, sex, cardiac arrest, type of myocardial infarction, culprit lesion, glycoprotein IIb/IIIa inhibitor, and oral P2Y12-receptor inhibitor and followed-up for 12 months. The study cohort consisted of 88 matched pairs. Thirty-day and 12-month mortality was 29.5% and 34.1% in cangrelor-treated patients and 36.4% and 47.1% in control group (P = 0.34 and P = 0.08, respectively). The rate of definite acute stent thrombosis was 2.3% in both groups. Moderate and severe bleeding events occurred in 21.6% in the cangrelor and 19.3% in the control group (P = 0.71). Patients treated with cangrelor more frequently experienced ≥1 TIMI flow grade improvement during PCI (92.9% vs. 81.2%, P = 0.02). CONCLUSION: Cangrelor treatment was associated with similar bleeding risk and significantly better TIMI flow improvement compared with oral P2Y12 inhibitors in CS patients undergoing PCI. The use of cangrelor in CS offers a potentially safe and effective antiplatelet option and should be evaluated in randomized trials.

Impact of smoking on cardiac magnetic resonance infarct characteristics and clinical outcome in patients with non-ST-elevation myocardial infarction.

Data derived from several studies suggest a better survival in smokers with acute myocardial infarction, a phenomenon referred to as the 'smoker's paradox'. We aimed to investigate the association of smoking with cardiac magnetic resonance (CMR) imaging determined infarct severity and major adverse cardiac events (MACE) defined as the occurrence of death, reinfarction, and congestive heart failure at 12 months in patients with non-ST-elevation myocardial infarction (NSTEMI) reperfused by early percutaneous coronary intervention (PCI). In this multicenter, registry study 311 NSTEMI patients underwent CMR imaging 3 (interquartile range [IQR] 2-4) days after PCI. Myocardial salvage index (MSI), infarct size (IS), and microvascular obstruction (MVO) as well as MACE rate were compared according to admission smoking status. Approximately one-third of patients were current smokers (n = 122, 39%). Smokers were significantly younger and less likely to have hypertension as compared to non-smokers (all p < 0.05). The extent of MSI (63.2, IQR 28.9-85.4 vs. 65.6, IQR 42.2-82.9, p = 0.30), and IS (7.2, IQR 2.3-15.7%LV vs. 7.0, IQR 2.2-12.4%LV, p = 0.27) did not differ significantly between smokers and non-smokers. Despite similar prevalence of MVO, MVO (%LV) was higher in smokers compared to non-smokers (2.0, IQR 0.9-4.7%LV vs. 1.2, IQR 0.7-2.2%LV, p = 0.03). MACE rates at 12 months were comparable in smokers and non-smokers (5.7% vs. 7.4%, p = 0.65). In NSTEMI patients, smoking is neither associated with increased myocardial salvage nor less severe myocardial damage. Clinical outcome at 12 months was similar in smokers and non-smokers.Trial registration NCT03516578.