Microaxial Flow Pump or Standard Care in Infarct-Related Cardiogenic Shock.

BACKGROUND: The effects of temporary mechanical circulatory support with a microaxial flow pump on mortality among patients with ST-segment elevation myocardial infarction (STEMI) complicated by cardiogenic shock remains unclear. METHODS: In an international, multicenter, randomized trial, we assigned patients with STEMI and cardiogenic shock to receive a microaxial flow pump (Impella CP) plus standard care or standard care alone. The primary end point was death from any cause at 180 days. A composite safety end point was severe bleeding, limb ischemia, hemolysis, device failure, or worsening aortic regurgitation. RESULTS: A total of 360 patients underwent randomization, of whom 355 were included in the final analysis (179 in the microaxial-flow-pump group and 176 in the standard-care group). The median age of the patients was 67 years, and 79.2% were men. Death from any cause occurred in 82 of 179 patients (45.8%) in the microaxial-flow-pump group and in 103 of 176 patients (58.5%) in the standard-care group (hazard ratio, 0.74; 95% confidence interval [CI], 0.55 to 0.99; P = 0.04). A composite safety end-point event occurred in 43 patients (24.0%) in the microaxial-flow-pump group and in 11 (6.2%) in the standard-care group (relative risk, 4.74; 95% CI, 2.36 to 9.55). Renal-replacement therapy was administered to 75 patients (41.9%) in the microaxial-flow-pump group and to 47 patients (26.7%) in the standard-care group (relative risk, 1.98; 95% CI, 1.27 to 3.09). CONCLUSIONS: The routine use of a microaxial flow pump with standard care in the treatment of patients with STEMI-related cardiogenic shock led to a lower risk of death from any cause at 180 days than standard care alone. The incidence of a composite of adverse events was higher with the use of the microaxial flow pump. (Funded by the Danish Heart Foundation and Abiomed; DanGer Shock ClinicalTrials.gov number, NCT01633502.).

Duration of Device-Based Fever Prevention after Cardiac Arrest.

BACKGROUND: Guidelines recommend active fever prevention for 72 hours after cardiac arrest. Data from randomized clinical trials of this intervention have been lacking. METHODS: We randomly assigned comatose patients who had been resuscitated after an out-of-hospital cardiac arrest of presumed cardiac cause to device-based temperature control targeting 36°C for 24 hours followed by targeting of 37°C for either 12 or 48 hours (for total intervention times of 36 and 72 hours, respectively) or until the patient regained consciousness. The primary outcome was a composite of death from any cause or hospital discharge with a Cerebral Performance Category of 3 or 4 (range, 1 to 5, with higher scores indicating more severe disability; a category of 3 or 4 indicates severe cerebral disability or coma) within 90 days after randomization. Secondary outcomes included death from any cause and the Montreal Cognitive Assessment score (range, 0 to 30, with higher scores indicating better cognitive ability) at 3 months. RESULTS: A total of 393 patients were randomly assigned to temperature control for 36 hours, and 396 patients were assigned to temperature control for 72 hours. At 90 days after randomization, a primary end-point event had occurred in 127 of 393 patients (32.3%) in the 36-hour group and in 133 of 396 patients (33.6%) in the 72-hour group (hazard ratio, 0.99; 95% confidence interval, 0.77 to 1.26; P = 0.70) and mortality was 29.5% in the 36-hour group and 30.3% in the 72-hour group. At 3 months, the median Montreal Cognitive Assessment score was 26 (interquartile range, 24 to 29) and 27 (interquartile range, 24 to 28), respectively. There was no significant between-group difference in the incidence of adverse events. CONCLUSIONS: Active device-based fever prevention for 36 or 72 hours after cardiac arrest did not result in significantly different percentages of patients dying or having severe disability or coma. (Funded by the Novo Nordisk Foundation; BOX ClinicalTrials.gov number, NCT03141099.).

Blood-Pressure Targets in Comatose Survivors of Cardiac Arrest.

BACKGROUND: Evidence to support the choice of blood-pressure targets for the treatment of comatose survivors of out-of-hospital cardiac arrest who are receiving intensive care is limited. METHODS: In a double-blind, randomized trial with a 2-by-2 factorial design, we evaluated a mean arterial blood-pressure target of 63 mm Hg as compared with 77 mm Hg in comatose adults who had been resuscitated after an out-of-hospital cardiac arrest of presumed cardiac cause; patients were also assigned to one of two oxygen targets (reported separately). The primary outcome was a composite of death from any cause or hospital discharge with a Cerebral Performance Category (CPC) of 3 or 4 within 90 days (range, 0 to 5, with higher categories indicating more severe disability; a category of 3 or 4 indicates severe disability or coma). Secondary outcomes included neuron-specific enolase levels at 48 hours, death from any cause, scores on the Montreal Cognitive Assessment (range, 0 to 30, with higher scores indicating better cognitive ability) and the modified Rankin scale (range, 0 to 6, with higher scores indicating greater disability) at 3 months, and the CPC at 3 months. RESULTS: A total of 789 patients were included in the analysis (393 in the high-target group and 396 in the low-target group). A primary-outcome event occurred in 133 patients (34%) in the high-target group and in 127 patients (32%) in the low-target group (hazard ratio, 1.08; 95% confidence interval [CI], 0.84 to 1.37; P = 0.56). At 90 days, 122 patients (31%) in the high-target group and 114 patients (29%) in the low-target group had died (hazard ratio, 1.13; 95% CI, 0.88 to 1.46). The median CPC was 1 (interquartile range, 1 to 5) in both the high-target group and the low-target group; the corresponding median modified Rankin scale scores were 1 (interquartile range, 0 to 6) and 1 (interquartile range, 0 to 6), and the corresponding median Montreal Cognitive Assessment scores were 27 (interquartile range, 24 to 29) and 26 (interquartile range, 24 to 29). The median neuron-specific enolase level at 48 hours was also similar in the two groups. The percentages of patients with adverse events did not differ significantly between the groups. CONCLUSIONS: Targeting a mean arterial blood pressure of 77 mm Hg or 63 mm Hg in patients who had been resuscitated from cardiac arrest did not result in significantly different percentages of patients dying or having severe disability or coma. (Funded by the Novo Nordisk Foundation; BOX ClinicalTrials.gov number, NCT03141099.).

Oxygen Targets in Comatose Survivors of Cardiac Arrest.

BACKGROUND: The appropriate oxygenation target for mechanical ventilation in comatose survivors of out-of-hospital cardiac arrest is unknown. METHODS: In this randomized trial with a 2-by-2 factorial design, we randomly assigned comatose adults with out-of-hospital cardiac arrest in a 1:1 ratio to either a restrictive oxygen target of a partial pressure of arterial oxygen (Pao2) of 9 to 10 kPa (68 to 75 mm Hg) or a liberal oxygen target of a Pao2 of 13 to 14 kPa (98 to 105 mm Hg); patients were also assigned to one of two blood-pressure targets (reported separately). The primary outcome was a composite of death from any cause or hospital discharge with severe disability or coma (Cerebral Performance Category [CPC] of 3 or 4; categories range from 1 to 5, with higher values indicating more severe disability), whichever occurred first within 90 days after randomization. Secondary outcomes were neuron-specific enolase levels at 48 hours, death from any cause, the score on the Montreal Cognitive Assessment (ranging from 0 to 30, with higher scores indicating better cognitive ability), the score on the modified Rankin scale (ranging from 0 to 6, with higher scores indicating greater disability), and the CPC at 90 days. RESULTS: A total of 789 patients underwent randomization. A primary-outcome event occurred in 126 of 394 patients (32.0%) in the restrictive-target group and in 134 of 395 patients (33.9%) in the liberal-target group (hazard ratio, 0.95; 95% confidence interval, 0.75 to 1.21; P = 0.69). At 90 days, death had occurred in 113 patients (28.7%) in the restrictive-target group and in 123 (31.1%) in the liberal-target group. On the CPC, the median category was 1 in the two groups; on the modified Rankin scale, the median score was 2 in the restrictive-target group and 1 in the liberal-target group; and on the Montreal Cognitive Assessment, the median score was 27 in the two groups. At 48 hours, the median neuron-specific enolase level was 17 µg per liter in the restrictive-target group and 18 µg per liter in the liberal-target group. The incidence of adverse events was similar in the two groups. CONCLUSIONS: Targeting of a restrictive or liberal oxygenation strategy in comatose patients after resuscitation for cardiac arrest resulted in a similar incidence of death or severe disability or coma. (Funded by the Novo Nordisk Foundation; BOX ClinicalTrials.gov number, NCT03141099.).

Recovery of cardiac function following COVID-19 - ECHOVID-19: a prospective longitudinal cohort study.

AIMS: The degree of cardiovascular sequelae following COVID-19 remains unknown. The aim of this study was to investigate whether cardiac function recovers following COVID-19. METHODS AND RESULTS: A consecutive sample of patients hospitalized with COVID-19 was prospectively included in this longitudinal study. All patients underwent an echocardiographic examination during hospitalization and 2 months later. All participants were successfully matched 1:1 with COVID-19-free controls by age and sex. A total of 91 patients were included (mean age 63 ± 12 years, 59% male). A median of 77 days (interquartile range: 72-92) passed between the two examinations. Right ventricular (RV) function improved following resolution of COVID-19: tricuspid annular plane systolic excursion (TAPSE) (2.28 ± 0.40 cm vs. 2.11 ± 0.38 cm, P < 0.001) and RV longitudinal strain (RVLS) (25.3 ± 5.5% vs. 19.9 ± 5.8%, P < 0.001). In contrast, left ventricular (LV) systolic function assessed by global longitudinal strain (GLS) did not significantly improve (17.4 ± 2.9% vs. 17.6 ± 3.3%, P = 0.6). N-terminal pro-B-type natriuretic peptide decreased between the two examinations [177.6 (80.3-408.0) ng/L vs. 11.7 (5.7-24.0) ng/L, P < 0.001]. None of the participants had elevated troponins at follow-up compared to 18 (27.7%) during hospitalization. Recovered COVID-19 patients had significantly lower GLS (17.4 ± 2.9% vs. 18.8 ± 2.9%, P < 0.001 and adjusted P = 0.004), TAPSE (2.28 ± 0.40 cm vs. 2.67 ± 0.44 cm, P < 0.001 and adjusted P < 0.001), and RVLS (25.3 ± 5.5% vs. 26.6 ± 5.8%, P = 0.50 and adjusted P < 0.001) compared to matched controls. CONCLUSION: Acute COVID-19 affected negatively RV function and cardiac biomarkers but recovered following resolution of COVID-19. In contrast, the observed reduced LV function during acute COVID-19 did not improve post-COVID-19. Compared to the matched controls, both LV and RV function remained impaired.

Deep sedation as temporary bridge to definitive treatment of ventricular arrhythmia storm.

BACKGROUND: Electrical storm and incessant ventricular tachycardia (VT) are characterized by the clustering of episodes of VT or ventricular fibrillation (VF) and are associated with a poor prognosis. Autonomic nervous system activity influences VT threshold, and deep sedation may be useful for the treatment of VT emergencies. METHODS: We reviewed data from conscious patients admitted to our intensive care unit (ICU) due to monomorphic VT, polymorphic VT or VF at our tertiary center between 2010 and 2018. RESULTS: A total of 46 conscious patients with recurrent ventricular arrhythmia, refractory to initial treatment, were referred to the ICU. The majority (n = 31) were stabilized on usual care. The remaining treatment-refractory 15 patients (57 years (range 9-74), 80% males, seven with implantable cardioverter-defibrillators) with VT/VF storm (n = 11) or incessant VT (n = 4) due to ischemic heart disease (n = 10), cardiomyopathy (n = 2), primary arrhythmia (n = 2) and one patient post valve surgery, were deeply sedated and intubated. A complete resolution of VT/VF within minutes to hours was achieved in 12 patients (80%), partial resolution in two (13%) and one (7%) patient died due to ventricular free-wall rupture. One patient with recurrent VT episodes needing repeated deep sedation developed necrotic caecum. No other major complications were seen. Thirteen (87%) patients were alive after a mean follow-up of 3.7 years. CONCLUSION: Deep sedation was effective and safe for the temporary management of malignant VT/VF refractory to usual treatment. In emergencies, deep sedation may be widely accessible at both secondary and tertiary centers and a clinically useful bridge to definitive treatment of VT.

Biomarkers predictive of late cardiogenic shock development in patients with suspected ST-elevation myocardial infarction.

BACKGROUND: Cardiogenic shock complicating ST-elevation myocardial infarction is characterised by progressive left ventricular dysfunction causing inflammation and neurohormonal activation. Often, cardiogenic shock develops after hospital admission. Whether inflammation and a neurohormonal activation precede development of clinical cardiogenic shock is unknown. METHODS AND RESULTS: In 93% of 2247 consecutive patients with suspected ST-elevation myocardial infarction admitted at two tertiary heart centres, admission plasma levels of pro-atrial natriuretic peptide, copeptin, mid-regional pro-adrenomedullin and stimulation-2 were measured on hospital admission. Patients were stratified according to no cardiogenic shock development and cardiogenic shock developed before (early cardiogenic shock) or after (late cardiogenic shock) leaving the catheterization laboratory. In total, 225 (10%) patients developed cardiogenic shock, amongst these patients late cardiogenic shock occurred in 64 (2.9%). All four biomarkers were independently associated with the development of late cardiogenic shock (odds ratio per two-fold increase in risk: 1.19-3.13) even when adjusted for the recently developed Observatoire Régional Breton sur l'Infarctus risk score for prediction of late cardiogenic shock development. Furthermore, pro-atrial natriuretic peptide, copeptin and mid-regional pro-adrenomedullin, but not stimulation-2, added significant predictive information, when added to the Observatoire Régional Breton sur l'Infarctus risk score (area under the receiver-operating characteristic curve, pro-atrial natriuretic peptide: 0.87, p=0.0008; copeptin: 0.86, p<0.05; mid-regional pro-adrenomedullin: 0.88, p=0.006). CONCLUSIONS: Pro-atrial natriuretic peptide, copeptin, mid-regional pro-adrenomedullin and stimulation-2 admission plasma concentration were associated with late cardiogenic shock development in patients admitted with suspected ST-elevation myocardial infarction. Pro-atrial natriuretic peptide, mid-regional pro-adrenomedullin and copeptin had independent predictive value for late cardiogenic shock development.

Percutaneous coronary intervention for acute MI does not prevent in-hospital development of cardiogenic shock compared to fibrinolysis.

BACKGROUND: It has been speculated that invasive revascularization prevents development of cardiogenic shock. Data from randomised trials comparing angioplasty with fibrinolysis on the development of cardiogenic shock are lacking. AIMS: To elucidate the effect of angioplasty on in-hospital development of cardiogenic shock compared to fibrinolysis. To evaluate whether mortality in patients who develop cardiogenic shock after treatment is dependent on revascularization strategy. METHODS AND RESULTS: DANAMI-2 randomly assigned 1572 STEMI patients to fibrinolysis (782 patients) or angioplasty (790 patients). Data on patients with in-hospital development of cardiogenic shock after randomisation were included. Of the 103 patients (6.6%) patients developing cardiogenic shock 57% were randomised to angioplasty with an unadjusted odds ratio of 1.39 (0.92-2.11, p=0.14). During the three year follow-up 58% of the total mortality was due to cardiogenic shock, and treatment strategy did not influence the risk associated with shock (hazard ratio of 1.05 (0.67-1.64) for angioplasty vs. fibrinolysis). CONCLUSIONS: Angioplasty does not prevent the in-hospital development of cardiogenic shock complicating acute MI compared to fibrinolysis. Cardiogenic shock is still the leading cause of death in patients hospitalised for acute MI. There was no difference in mortality, with regards to treatment strategy in patients developing cardiogenic shock after the initial treatment.

B-type natriuretic peptide and its molecular precursor in myocardial infarction complicated by cardiogenic shock.

BACKGROUND: Plasma measurement of cardiac natriuretic peptides and their biosynthetic precursors is helpful in chronic heart failure patients. In contrast, information on circulating B-type natriuretic peptide (BNP) and its molecular precursor (proBNP) in patients with cardiogenic shock is scarce. We therefore examined proBNP-derived peptides in plasma from patients with myocardial infarction complicated by cardiogenic shock. METHODS AND RESULTS: Patients were referred for early, invasive therapy because of myocardial infarction complicated by cardiogenic shock (n = 13). Plasma proBNP was measured with an automated assay (NT-proBNP) and an in-house radioimmunoassay (proBNP); BNP concentrations were quantitated with an immunoradiometric assay. The median NT-proBNP concentration was 8.2-fold higher than the corresponding BNP concentration (873 pmol/L [range 41-12,486] versus 107 pmol/L [1-1041], P < .001). Moreover, the NT-proBNP concentration was 3.3-fold higher compared with proBNP (268 pmol/L [19-12,220], P < .01). Despite the molar differences, there was a strong correlation between NT-proBNP and proBNP (r = 0.84, P < .0001) and BNP (r = 0.82, P < .0001) concentrations. Gel filtration chromatography suggested that the proBNP immunoreactivity reflect a molecular form larger than the N-terminal 1-76 fragment. CONCLUSIONS: The study reveals the plasma profile of proBNP-derived peptides during myocardial infarction complicated by cardiogenic shock. Peripheral concentrations of NT-proBNP, proBNP, and BNP were highly correlated despite marked differences between assays. The results also suggest an increase in cardiac proBNP processing after myocardial infarction and cardiogenic shock.