Early Escalation of Mechanical Circulatory Support Stabilizes and Potentially Rescues Patients in Refractory Cardiogenic Shock.

BACKGROUND: Limited progress has been made in the management of cardiogenic shock (CS). Morbidity and mortality of refractory CS remain high. The effects of mechanical circulatory support (MCS) are promising, although many aspects are elusive. We evaluated efficacy and safety of early combined MCS (Impella microaxial pump + venoarterial extracorporeal membrane oxygenation [VA-ECMO]) in refractory CS and aimed to determine factors for decision-making in combined MCS. METHODS AND RESULTS: We analyzed 69 consecutive patients with refractory CS from our registry requiring combined MCS. In 12 cases, therapy was actively withdrawn according to patient's will. Patients were severely sick (Survival After Venoarterial ECMO score mean±SD, -8.9±4.4) predicting 30% in-hospital survival; ventilation 94%, dialysis 56%. Impella pumps and VA-ECMO were combined early (duration of combined MCS: median 94 hours; interquartile range, 49-150 hours). Early MCS escalation stabilized patients rapidly, reducing number and doses of catecholamines (P<0.05 versus baseline) while hemodynamics improved. Reflecting an improved microcirculation, lactate levels normalized within 24 hours (P<0.05 versus baseline). Despite refractory CS and disease severity, survival was favorable (on MCS 61%, 30 days 49%, 6 months 40%). In multivariate Cox-regression, duration of shock-to-first device (hours, hazard ratio, 1.05 [95% CI, 1.01-1.08]; P=0.007) and lactate levels after 12 hours of MCS (hazard ratio, 1.28 [95% CI, 1.09-1.51]; P=0.002) independently predicted survival. Additional right ventricular failure predisposed to futility (hazard ratio, 8.48 [95% CI, 1.85-38.91]; P=0.006). CONCLUSIONS: The early and consequent combination of MCS by Impella microaxial pumps and VA-ECMO enables stabilization and may rescue high-risk patients with refractory CS at low overall risk. Independent predictors of survival may guide prognostication, decision-making, and allocation of medical resources.

Assessment of myocardial function using MRI-based feature tracking in adults after atrial repair of transposition of the great arteries: Reference values and clinical utility.

BACKGROUND: Echocardiographic parameters of ventricular deformation of the systemic right ventricle (sRV) predict adverse clinical outcome in patients after atrial repair of transposition of the great arteries (TGA). We assessed myocardial deformation on cardiac MRI (CMR) and correlated these with clinical and conventional CMR parameters in TGA patients. METHODS: Retrospective analysis of CMR studies in 91 TGA patients (66% male; mean age 30.1±5.1years) at two tertiary adult congenital heart centers was conducted. Myocardial deformation was assessed by CMR-based feature tracking (FT), providing longitudinal (LS), radial (RS), and circumferential (CS) global strain for the sRV and the subpulmonary left ventricle. A subgroup of optimal TGA was defined (NYHA class I, NT-proBNP <300pg/ml, max. exercise work load ≥100watt, no significant clinical events) as a reference cohort. RESULTS: There was a significant correlation between FT and conventional CMR parameters. Left ventricular ejection fraction (LVEF) correlated significantly with LV LS, RS, and CS (r between 0.24 and 0.34, p values between 0.03 and 0.005). sRVEF correlated with RV CS (r=0.56, p<0.001), and RV RS (r=0.32, p=0.007). QRS duration showed a negative correlation with RV CS (r=-0.53, p<0.001), LV RS (r=-0.34, p=0.008), and LV CS (r=-0.34, p=0.006). Reference values for the novel FT method in clinically optimal TGA patients are provided. CONCLUSION: Assessment of myocardial function using CMR-based FT is feasible in TGA patients. FT measurements related to important prognostic clinical parameters. Furthermore, we provide for the first time reference values for TGA patients in an optimal clinical status.

Platelet inhibition with prasugrel in patients with acute myocardial infarction undergoing therapeutic hypothermia after cardiopulmonary resuscitation.

Acute myocardial infarction (AMI) is the leading cause for out-of-hospital cardiac arrest. Therapeutic hypothermia improves neurological outcome in combination with early revascularisation, but seems to affect clopidogrel responsiveness. The more potent thienopyridine prasugrel has not yet been sufficiently evaluated during therapeutic hypothermia. We investigated 23 consecutive AMI patients (61 ± 11 years) following out-of-hospital resuscitation undergoing revascularisation and therapeutic hypothermia. Prasugrel efficacy was assessed by the platelet-reactivity-index (PRI) before and 2, 4, 6, 12, 24, 48, and 72 hours (h) following a loading dose of 60 mg via a gastric tube. Mean PRI (± SD) was 70 ± 12 % prior to loading and 60 ± 16 % (2 h, ns), 52 ± 21 % (4 h, p< 0.01), 42 ± 26 % (6 h, p< 0.01), 37 ± 21 % (12 h, p< 0.01), 27 ± 23 % (24 h, p< 0.01), 18 ± 14 % (48 h, p< 0.01), and 13 ± 10 % (72 h, p< 0.01) after loading. Sufficient platelet inhibition occurred later compared to stable AMI patients (6 h vs 2 h); however, high on-treatment platelet reactivity significantly decreased over time and was non-existent after 72 h (PRI> 50 %: 2 h: 72 %, 4 h: 52 %, 6 h: 43 %, 12 h: 29 %, 24 h: 17 %, 48 h: 5 %, 72 h: 0 %). There was no relation between 30-day mortality rate (26 %) and PRI values. Prasugrel significantly reduced platelet reactivity even during vasopressor use, analgosedation and therapeutic hypothermia. Despite a significant delay compared to stable AMI patients, sufficient platelet inhibition was reached in 83 % of patients within 24 h. Therefore, prasugrel administration via gastric tube might be a useful therapeutic strategy in these patients at high risk, providing potent and effective P2Y12 inhibition.

Rationale and design of a randomized, controlled multicentre clinical trial to evaluate the effect of bromocriptine on left ventricular function in women with peripartum cardiomyopathy.

BACKGROUND: Peripartum cardiomyopathy (PPCM) is an idiopathic heart disease that develops in the last month of pregnancy and/or the first months following delivery in previously healthy women and may lead to acute heart failure. A cleaved fragment of the nursing hormone prolactin is considered essential in the pathophysiology of PPCM. To date, no specific therapy has been tested for PPCM in a randomized controlled trial of adequate size. AIMS: The purpose of this trial is to investigate the safety of the dopamin-D2-receptor agonist bromocriptine and its effects on left ventricular (LV) function in women with PPCM. METHODS: This is an 11 center German trial with a prospective randomized controlled open-label design. The trial enrolls females with newly diagnosed PPCM according to European Society of Cardiology criteria with a LV ejection fraction (LVEF) <35 %. Patients are randomized 1:1 to either best supportive care (BSC) including standard heart failure therapy plus 8 weeks of bromocriptine therapy (2.5 mg b.i.d. for 14 days and 2.5 mg q.d. from day 15 to 56) or to BSC plus 1 week of low-dose bromocriptine (2.5 mg q.d.) with anticoagulant therapy at a prophylactic dose administered during the period of bromocriptine treatment in both groups. The primary endpoint is change in LVEF from baseline to 6 months follow-up as assessed by cardiac magnetic resonance imaging (or echocardiography if CMR is not tolerated). The secondary endpoints are hospitalization for worsening heart failure, heart transplantation, and all-cause mortality during follow-up or a combination of these endpoints. A total of 60 patients will be recruited (including 6 potential dropouts) giving a power of 0.9 for an expected LVEF change of 10.8 % between treatment groups at 6 months. PERSPECTIVE: This trial will provide important knowledge on potential benefits and safety of prolonged inhibition of prolactin release with bromocriptine in addition to standard heart failure therapy in newly diagnosed PPCM. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00998556.

Cardiac awake extracorporeal life support-bridge to decision?

Severe acute heart failure requires immediate intensive care unit (ICU) treatment, but prognosis and outcome of further treatment regimens largely depends on the preprocedural status of the patient. Especially, multiorgan failure including mechanical ventilation are unfavorable predictors of clinical outcome. Here, we report a strategy of immediate initiation of extracorporeal life support (ECLS) in awake and spontaneously breathing patients with acute heart failure to achieve early multiorgan recovery and gain sufficient time for further treatment planning. Twenty-three patients with severe cardiac failure refractory to standard medical management underwent ECLS treatment, after first clinical signs of cardiac failure appeared to avoid mechanical ventilation. Hemodynamic parameters and renal and liver functions were monitored. Outcome at 1 and 6 months was determined. Patients 46.1 ± 15.5 years of age were placed on ECLS due to various underlying diagnosis: ischemic heart disease (n = 6), dilatative cardiomyopathy (n = 4), myocarditis (n = 2), graft failure following heart transplantation (n = 6), or other diseases (n = 5). ECLS lasted 11.9 ± 12.9 days. Hemodynamic stabilization was achieved immediately after ECLS initiation. Vasopressors were reduced subsequently and the cardiac situation improved indicated by central venous saturation, which increased from 38.5 ± 11.3% before to 74.26 ± 8.4% (P < 0.0001) 24 h after ECLS initiation. Similarly, serum lactate levels decreased from 4.7 ± 4.6 to 1.7 ± 1.51 mmol/L (P = 0.003). Cumulative 30-day survival was 87.5%, and 6-month survival was 70.8%. In acute cardiac failure, early ECLS treatment is a safe, feasible treatment in awake patients allowing a gain of time for final decision. Moreover, this strategy avoids complications associated with sedation and mechanical ventilation and leads to recovery of secondary organ function, enabling destination therapy.

Prognostic implication of right ventricular involvement in peripartum cardiomyopathy: a cardiovascular magnetic resonance study.

AIMS: Peripartum cardiomyopathy (PPCM) is a major cause of acute heart failure in the peripartum period and considered potentially life threatening. While many aspects of its clinical profiles have been frequently reported, functional analysis, in particular of the right ventricle, and tissue characterization by cardiovascular magnetic resonance (CMR) imaging have been only sporadically described. The aim of the present study was to analyse pathological alterations and their prognostic relevance found in CMR imaging of patients newly diagnosed with PPCM. METHODS AND RESULTS: In this multicenter study 34 patients with confirmed PPCM underwent CMR imaging at the time of diagnosis and at 5 ± 1 months follow-up. Cine imaging of PPCM patients showed moderate to severe reduction of systolic left ventricular (LV) function (mean LVEF: 29.7 ± 12.8%). In 35% of the patients right ventricular (RV) systolic function was also reduced with a mean RVEF of 42.9 ± 13.9%. Dilatation of the LV was observed in 91% (mean LV-EDV/BSA 128.5 ± 32.1 mL/m2), and dilatation of the RV was present in 24% (mean RV-EDV/BSA 87.4 ± 18.5 mL/m2) of the patients. Focal non-ischemic late gadolinium enhancement (LGE) was visible in 71%, and regional wall motion abnormalities were evident in 88% of the patients. LGE and wall motion abnormalities were predominantly located in the anteroseptal and basal to midventricular segments. RV dysfunction at baseline was associated with reduced probability of full cardiac recovery at 5 ± 1 months follow-up. CONCLUSIONS: Besides LV systolic dysfunction, RV dysfunction and dilatation are observed in about one third of PPCM patients at the time of diagnosis. RV dysfunction is associated with unfavourable outcome. A distinct pattern of LV wall motion abnormalities and myocardial scar is evident in most PPCM patients. The present study may help to establish a set of CMR criteria suitable for diagnosis in patients with suspected PPCM and may add further knowledge to the pathology of the disease.

Relation of diastolic and systolic function, exercise capacity and brain natriuretic peptide in adults after Mustard procedure for transposition of the great arteries.

OBJECTIVES: To evaluate the relation of echocardiographic parameters of diastolic function, exercise capacity (expressed as peakVO(2)) and NT-proBNP in patients with transposition of the great arteries (TGA) and Mustard procedure. METHODS: Diastolic function was determined by measuring tricuspid flow velocities (Ea/Aa ratio), isovolumic relaxation time (IVRT), and deceleration time (DT). E/Ea ratios were calculated. For assessment of systolic function, CMR was applied. RESULTS: E/A (r = 0.07, p = 0.66), E/Ea medial (r = 0.03, p = 0.84), E/Ea lateral (r = -0.01, p = 0.92), IVRT (r = -0.13, p = 0.44), and DT (r = -0.05, p = 0.76) were not correlated with peakVO(2). NT-proBNP showed a significant correlation with IVRT (r = 0.44, p = 0.004) and Ea/Aa medial (r = -0.34, p = 0.025). No correlation was found between RV systolic function and peakVO(2) (r = 0.07, p = 0.63). CONCLUSIONS: Exercise capacity in patients with TGA and Mustard procedure is not related to echocardiographic parameters of diastolic function. NT-proBNP is associated with selected echocardiographic parameters of diastolic function.

Effect of catecholamines on intracellular cytokine synthesis in human monocytes.

Proinflammatory cytokines produced by monocytes, like Interleukin-6 (IL-6), Interleukin-8 (IL-8), and tumor necrosis factor (TNF-alpha) are known for their pivotal role in the initiation of the inflammatory response following cardiopulmonary bypass (CPB). Catecholamines like epinephrine (Epi) and norepinephrine (Nor) are often necessary to stabilize the cardiac function in the early postoperative period and may influence the cytokine expression in monocytes. In this study we investigated the effects of Epi and Nor on IL-6, IL-8 and TNF-alpha expression in human monocytes stimulated with lipopolysaccharide (LPS) in whole blood, analyzed intracellularly by flow cytometry. Kinetics of intracellular proinflammatory cytokine production and LPS ED(50) were obtained. To simulate different stages of inflammation in vivo, varying concentrations of LPS (0.2 ng/ml, 1 ng/ml and 10 ng/ml) were used for stimulation. After a stimulation with LPS TNF-alpha was the first produced cytokine, followed by IL-8 and IL-6. All cytokines peaked from 3 h to 6 h. Epi and Nor had comparable effects on the expression of IL-6, IL-8 and TNF-a in monocytes. Both inhibited IL-6 and TNF-alpha expression in a concentration dependent manner whereas IL-8 expression remained unchanged. We conclude that monocytes are targets for Epi and Nor concerning their cytokine expression. The inhibiting effects of Nor and Epi were almost identical for all cytokines. Cytokine expression was affected most at low LPS concentrations.