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Cardiogenic Shock Due to End-Stage Heart Failure and Acute Myocardial Infarction

Characteristics and Outcome of Temporary Mechanical Circulatory Support

Lim, Hoong Sern; Howell, Neil

doi: 10.1097/SHK.0000000000001052
Clinical Science Aspects
Free

Background: Mechanical circulatory support (MCS) is increasingly used in cardiogenic shock, but outcomes may differ between patients with acute myocardial infarction (AMI) or end-stage heart failure (ESHF). This study aimed to describe the characteristics of patients with cardiogenic shock due to AMI and ESHF.

Methods: Single-center study of consecutive patients with cardiogenic shock due to AMI (n = 26) and ESHF (n = 42) who underwent MCS (extracorporeal life support, Impella or temporary ventricular assist devices). Arterial and venous O2 content and CO2 tension (PCO2), O2-hemoglobin affinity (P50) were measured. Veno-arterial difference in PCO2/arterio-venous difference in O2 content ratio was derived. Acid–base balance was characterized by the Gilfix method. MCS-related complications that required intervention or surgery were collected.

Results: Patients with ESHF had lower ejection fraction, higher right and left-sided filling pressures, pulmonary artery pressure and vascular resistance, lower oxygen delivery (DO2) compared with AMI, which was not fully compensated by the increased hemoglobin P50. As a result, patients with ESHF had higher veno-arterial difference in PCO2 relative to arterio-venous difference in O2 content. Despite greater anerobic metabolism, patients with ESHF had less severe metabolic acidosis and base deficit compared with AMI, predominantly due to differences in strong ions.

Conclusion: The cardiogenic shock phenotype in ESHF was distinct from AMI, characterized by higher filling and pulmonary artery pressures, lower DO2, greater anaerobic metabolism but less severe metabolic acidosis.

University Hospital Birmingham, Edgbaston, Birmingham, UK

Address reprint requests to Hoong Sern Lim, MD, Queen Elizabeth Hospital Birmingham, University Hospital Birmingham NHS Foundation Trust, Edgbaston, Birmingham, UK. E-mail: sern.lim@uhb.nhs.uk

Received 22 July, 2017

Revised 7 September, 2017

Accepted 27 October, 2017

The authors report no conflicts of interest.

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INTRODUCTION

Temporary mechanical circulatory support (MCS) such as Impella, veno-arteral extracorporeal membrane oxygenation (VA-ECMO), and surgical temporary ventricular assist devices are increasingly used to bridge patients with cardiogenic shock to recovery, transplantation or durable left ventricular assist devices (LVAD). However, outcomes are highly variable in part due to variability in patient selection (1). Hemodynamic and metabolic differences between patients with cardiogenic shock of different aetiology, such as acute myocardial infarction (AMI) and end-stage chronic heart failure (ESHF) due to an underlying ischemic or nonischemic cardiomyopathy may contribute to the variability in outcomes, as the chronicity in the latter may allow the development of compensatory mechanisms in the face of long-standing low cardiac output; ubiquitous use of neurohormonal antagonists in ESHF may blunt the response to shock (2); and chronic high dose diuretic therapy also contributes to metabolic abnormalities (3), which may be absent in AMI. However, there are limited data on the cardiogenic shock phenotype based on the aetiology (ESHF and AMI). Therefore, the objective of this study was to characterize patients with cardiogenic shock due to ESHF and AMI. Hemodynamic and metabolic (lactate) parameters are often used as surrogates of hypoperfusion (4), but the ratio of veno-arterial carbon dioxide tension (PCO2) difference to arteriovenous oxygen (O2) content difference (5, 6) may be a more reliable measure of anaerobic metabolism, although this parameter has not been studied in cardiogenic shock. Hence, we aimed to characterize these metabolic metabolic parameters that are typically associated with anaerobic metabolism in patients with cardiogenic shock due to ESHF and AMI.

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METHODS

Study design and patient population

This single-center study included consecutive patients with severe cardiogenic shock due to AMI or ESHF, who underwent MCS from January 2012 to January 2016. The following patients were included: cardiogenic shock following acute myocardial infarction with or without ST-segment elevation (AMI group); and cardiogenic shock in patients with established heart failure and reduced left ventricular ejection fraction (LVEF) (an end-stage cardiomyopathy or ESHF group). The following patients were excluded from this study: patients with mechanical complication from AMI, cardiogenic shock of other aetiology and/or MCS for other indications (e.g., post-cardiotomy or post-transplant graft dysfunction) (Fig. 1).

Fig. 1

Fig. 1

In our institution, MCS are used in patients with cardiogenic shock to bridge patients to decision, candidacy or in some cases to directly bridge to heart transplantation or LVAD following multidisciplinary team discussion. Patients with worsening cardiogenic shock with mean arterial blood pressure of <60 mm Hg, end-organ hypoperfusion, cardiac index of less than 2.0 L·min−1·m−2 and right atrial and pulmonary-capillary occlusion pressure of at least 10 mm Hg and 20 mm Hg respectively despite escalating inotropes/vasopressors would be considered for MCS. Vascular access for Impella CP and/or VA-ECMO was obtained via the femoral vessels in all cases, with a distal perfusion cannula routinely inserted with VA-ECMO as previously described (7). Surgical MCS were achieved by sternotomy and direct cannulation of the right atrium and pulmonary artery (right ventricular support), and LV and aorta (LV support).

The inotrope score was used to quantify support from vasoactive drugs (Inotrope score= doses of dopamine + dobutamine in μg·kg−1·min−1 + [(epinephrine + norepinephrine + isoproterenol in μg·kg−1·min−1) × 100] + [milrinone μg·kg−1·min−1 × 15]) (8). Specific MCS-related complications that were evaluated in this study included (ischemic or hemorrhagic) strokes and complications that required surgical/procedural interventions: bleeding requiring reopening or wound exploration, device failure, surgical/percutaneous venting of the LV due to severe pulmonary oedema, vascular complications that required surgery including amputation and hemolysis resulting in renal failure that required device manipulation/removal.

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Pulmonary artery catheter studies

Pulmonary artery catheters were used routinely in all patients with cardiogenic shock under consideration for MCS. Pulmonary hemodynamic data including right atrial (RAP), pulmonary artery systolic (PASP), diastolic (PADP) and mean (mPAP), and pulmonary artery occlusion (PAOP) pressures were measured as previously described (9). Cardiac output was taken as the mean of three thermodilution measurements and indexed for BSA (cardiac index, CI). Cardiac power index was calculated as the product of mean arterial blood pressure and CI divided by 451 (10). Pulmonary vascular resistance (PVR) was calculated as the ratio of transpulmonary gradient and CO. Pulmonary capacitance (PCap) was the stroke volume divided by pulmonary pulse pressure.

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Blood gas analyses oxygen delivery

Immediately before or after completion of thermodilution measurements, arterial and mixed venous blood samples were drawn together at the same time for the determination of arterial oxygen tension (PaO2), arterial carbon dioxide tension (PaCO2), mixed venous oxygen (PvO2) and carbon dioxide tension (PvCO2), arterial (SaO2) and mixed venous oxygen saturation (SvO2). Hemoglobin (Hb) concentration was also measured. Oxygen–hemoglobin affinity was expressed as the oxygen tension at which blood is 50% saturated with oxygen (P50). The P50 was calculated from the measured oxygen saturation and oxygen tension of mixed venous blood by the Severinghaus method (11).

The following parameters were derived from these measurements:

  • Arterial blood oxygen content: CaO2=(1.34×SaO2×Hb)+(0.003×PaO2)
  • Mixed venous blood oxygen content: CvO2=(1.34×SvO2×Hb)+(0.003×PvO2)
  • Arterial-venous oxygen content difference: C(a-v)O2=CaO2–CvO2
  • Oxygen delivery: DO2=cardiac output × CaO2
  • Oxygen extraction ratio: O2ER=(CaO2–CvO2)/CaO2
  • Carbon dioxide tension difference: ΔPCO2=PvCO2–PaCO2

Global O2 consumption (VO2) reduces under conditions of tissue hypoxia, which results in corresponding reduction in aerobic CO2 production. However, anaerobic CO2 production continues mostly through buffering of excess protons by bicarbonate ions. Thus, total CO2 production (VCO2) is reduced to a lesser extent compared to the reduction in O2 consumption, resulting in an increase in the VCO2/VO2 ratio under hypoxic conditions. According to the Fick equation, VO2 is the product of CO and arterio-venous O2 content difference (C(a-v)O2), and VCO2 similarly is the product of CO and veno-arterial CO2 content difference (C(v-a)CO2). Hence, the VCO2/VO2 ratio can be expressed as the ratio of C(v-a)CO2/C(a-v)O2. CO2 content has a curvilinear relationship to CO2 tension (PCO2), and this relationship is affected by O2 saturation (Haldane effect) and acidosis (12). CO2 content is further increased at low flow states due to the phenomenon of CO2 stagnation. At higher CO2 content, the CO2 content–PCO2 relationship flattens, resulting in greater PCO2 per unit change in CO2 content. In this study, we used CO2 tension difference (ΔPCO2) as a surrogate for C(v-a)CO2, as: CO2 tension is linearly related to CO2 content over the physiological range (steep part of the CO2 dissociation curve), ΔPCO2 is greater at low output states, and calculation of CO2 content is cumbersome and more susceptible to error (13). By extension the ratio of ΔPCO2/C(a-v)O2 ratio was used as a marker of global anaerobic metabolism (14).

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Acid–base quantification

We quantified the metabolic acid–base disorder in cardiogenic shock using the base-excess (BE) method described by Gilfix et al. (15), which was based on the fundamental principles of Stewart physicochemical model (16). In brief, the physicochemical model identified strong ions, weak acids, and partial pressure of CO2 as the three independent determinants of acid–base disorders. Accordingly, the Gilfix method proposed that non-respiratory acid–base disturbances may be attributed to: changes in strong ions due to free water deficit or excess (determined by changes in sodium concentration) and changes in chloride (Cl) concentration; changes in protein charges (mainly albumin); and presence of organic unmeasured anions. Hence,

where BEmeas is the measured BE;

BEfw is the free water-related BE = 0.3 × ([Na]-140);

BECl is the chloride-related BE = 102-corrected Cl;

(corrected Cl = (140/[Na]) × [Cl])

BEalb is the albumin-related BE = 0.34 × (42-[Albumin])

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Statistical analysis

Continuous variables are reported as mean ± standard deviation (SD) or median (interquartile range, IQR) and categorical variables as proportions. Characteristics of the 2 groups of patients (AMI and ESHF) were compared by t test or Mann–Whitney U test for parametric and non-parametric data respectively. Fisher exact test was used for categorical variables. All statistical analyses were performed using R (version 3.1.1) and a two-sided P value of <0.05 was considered statistically significant.

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RESULTS

This study included 68 patients (26 AMI and 42 ESHF) with cardiogenic shock who underwent MCS. Of the 42 patients with ESHF, 12 and 30 patients had underlying ischemic and nonischemic dilated cardiomyopathy respectively. The causes of the nonischemic cardiomyopathy were idiopathic in the majority (28/30) and chemotherapy-related in the remaining 2 patients. The median duration of heart failure was 19 (17–23) months. All the patients with AMI underwent percutaneous revascularization to the left anterior descending artery, and additional intervention to the left main stem in three patients and at least one other coronary artery in eight patients. Patients with ESHF had lower LVEF but no significant difference in CI or cardiac power index compared with patients with AMI (Table 1). Right and left-sided filling pressures and pulmonary artery pressures were higher in patients with ESHF compared with AMI (Fig. 2), resulting in higher pulmonary vascular resistance (3.72 ± 0.52 vs 2.23 ± 0.23 WU, P < 0.001) and lower pulmonary capacitance (1.33 ± 0.20 vs 2.18 ± 0.28 mL/mm Hg, P < 0.001). A greater proportion of patients with ESHF were supported with biventricular assist devices.

Table 1

Table 1

Fig. 2

Fig. 2

There were also differences in acid–base balance due to differences in strong ions, albumin, and unmeasured anions between patients with ESHF and AMI (Table 2). Patients with cardiogenic shock due to ESHF had greater “dilutional acidosis” (excess-free water) and unmeasured anions, which were balanced by hypochloremic alkalosis and hypoalbuminemia, resulting in relatively modest acidemia. In contrast, patients with cardiogenic shock due to AMI had greater acidemia driven largely by unmeasured anions (Fig. 3).

Table 2

Table 2

Fig. 3

Fig. 3

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Oxygen delivery, ΔPCO2/C(a-v)O2 ratio, and clinical outcomes

Global oxygen delivery, DO2 was lower in patients with ESHF due to lower Hb. The lower DO2 in ESHF was partly compensated by greater O2 extraction, facilitated by the higher P50 (Table 3). DO2 was inversely related to P50 (r = −0.563, P < 0.001) in patients with ESHF. The veno-arterial PCO2 difference was greater in patients with ESHF, primarily due to higher venous PCO2. The higher PCO2 gradient, coupled with greater O2 extraction, resulted in significantly higher ΔPCO2/C(a-v)O2 ratio in patients with ESHF compared with AMI. The ΔPCO2/C(a-v)O2 ratio correlated with lactate (r = 0.290, P = 0.016) and inversely with DO2 (r = −0.550, P < 0.001), but no significant correlation with cardiac power index.

Table 3

Table 3

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Clinical outcomes

The 68 patients underwent a total of 94 temporary MCS procedures. Twenty-two patients underwent more than one temporary MCS bridging—6 patients with AMI and 16 with ESHF. Twenty-five of the 68 patients suffered complications that required surgical intervention. Two vascular complications led to below-knee amputations, both in patients on VA-ECMO support. Three patients with ESHF (none in the AMI group) suffered severe pulmonary oedema, who required LV decompression. There were no lower limb amputations related to Impella. Twenty, nine, and seven patients were bridged to transplantation, LVAD and recovery respectively. Thirty-five (27 and 8 patients with ESHF and AMI, respectively) of the 68 patients died (including 2 post-transplant and 1 post-LVAD).

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DISCUSSION

To our knowledge, this is the first study to characterize the phenotype of patients with cardiogenic shock based on the aetiology. This study has shown that patients with cardiogenic shock due to ESHF have a phenotype that was distinct from AMI. First, patients with ESHF had lower Hb, which resulted in lower DO2 compared with AMI. Anaemia is well recognized in patients with chronic HF (17), and has been attributed to a number of different causes. Hemodilution may be contributory in a significant proportion of patients (18), and may be relevant in our patients in light of the higher filling pressures and hyponatremia. Other possible causes include antagonism of the renin–angiotensin system (19) (angiotensin II has direct stimulatory effect on bone marrow erythrocyte precursors (20)), coexisting chronic renal impairment (21), and activation of pro-inflammatory cytokines in HF (22) (with consequent inhibition of erythropoiesis (23)).

Second, the lower DO2 that was partially compensated by increased O2 extraction. Reduced oxygen–hemoglobin affinity is a recognized compensatory mechanism in HF, facilitated by increase in 2,3 diphosphoglycerate (24, 25). However, this adaptive response could not fully compensate for the marked reduction in DO2, which was associated with higher ΔPCO2/C(a-v)O2 ratio. The higher ΔPCO2/C(a-v)O2 ratio was, to a large extent, related to higher PvCO2. The higher PvCO2 is likely to be multifactorial. Regional differences in blood flow and perfusion are common in shocked states, and low flow and hypoperfused regions may contribute disproportionately to increased CO2 content due to the combination of acidosis, CO2 stagnation, and the Haldane effect (26). The CO2 content–PCO2 relationship is relatively flat at higher CO2 content levels, which results in further disproportionate increase in PCO2. Differences in CO2 production may also be contributory and cannot be excluded in the absence of direct CO2 production measurements.

Based on previous studies (27), higher ΔPCO2/C(a-v)O2 ratio would suggest greater anaerobic metabolism. The finding of lower lactate levels in patients with ESHF compared with AMI may appear inconsistent with this suggestion of greater anaerobic metabolism. However, lactatemia may not simply reflect anaerobic glycolysis. Indeed, adrenergic stimulation with catecholamines and beta-blocker therapy are associated with increase and decrease in lactatemia respectively (28, 29). It is possible that neurohormonal antagonists and beta-blocker use in patients with ESHF may have contributed to the lower lactatemia in ESHF.

Third, there were notable differences in base deficits and acidemia between patients with ESHF and AMI. Chloride as a strong anion is a determinant of acid–base balance. Hypochloremia relative to total cations increases strong ion difference with resultant alkalosis and compensated for the accumulation of unmeasured anions, resulting in more modest base deficits and acidemia. Hypochloremia in patients with ESHF in this study is consistent with other reports of patients with advanced HF and likely to be multifactorial (30, 31). Hypochloremia may have a direct pathophysiological role in the modulation of the cardiorenal axis and congestion in HF, as chloride suppresses plasma renin activity via direct action on the macular densa (32), and decreases the availability of both sodium–potassium–chloride cotransporter and sodium chloride cotransporter (33). However, hypochloremia may also be a marker of neurohormonal activation, water retention, and diuretic therapy. Arterial “underfilling” triggers sympathetic activation, renin–angiotensin system, and nonosmotic release of arginine vasopressin, with consequent alteration in renal hemodynamics and water retention (34). In addition, loop diuretics inhibit the sodium-potassium-chloride cotransporter and reduce reabsorption of sodium and chloride, which contributes to hypochloremia (35).

Our approach to MCS in severe cardiogenic shock has previously been described (36). The pulmonary hemodynamics in patients with AMI described in our study are comparable to that reported by the SHOCK trial (37), indicating dominant left ventricular failure. In contrast, patients with ESHF had more severe biventricular dysfunction. The more severe right heart failure is evidenced by the higher right-sided filling pressures, which may be related to chronic elevation in pulmonary vascular resistance. As a result, biventricular support modalities were used more frequently in patients with ESHF. The more invasive biventricular support may have contributed to the higher incidence of vascular and bleeding complications and the poorer outcomes in ESHF. In addition, more patients with ESHF underwent multiple MCS bridging, as none of the patients demonstrated recovery of cardiac function, unlike some of the patients with AMI. These differences highlight the complexities of MCS in patients with ESHF compared with AMI.

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Study limitations

There are a number of notable limitations to this study. First, this is a single-center study with a relatively small number of highly selected patients. Nonetheless, the current study is one of the largest series of meticulously characterized patients with cardiogenic shock due to ESHF. Second, this was not a prospective or randomized study of the timing and/or the modality of MCS. Future studies should evaluate the use of MCS based on the ΔPCO2/C(a-v)O2 ratio. Third, we included only “surgical” complications. Other complications such as bleeding that did not require intervention or infections treated with antimicrobial therapy were not included. Therefore, the impact of these complications on outcome could not be determined.

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CONCLUSION

Patients with cardiogenic shock due to ESHF have a phenotype that is distinct from AMI, characterized by higher filling and pulmonary artery pressures, lower DO2, partially compensated by higher P50 and more severe anaerobic metabolism but less severe metabolic acidosis due to hypochloremia. Understanding these phenotypic differences may guide intervention based on the underling aetiology of cardiogenic shock.

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REFERENCES

1. Lim HS, Howell N, Ranasinghe A. Extracorporeal life support physiological concepts and clinical outcomes. J Card Fail 23 2: 181–196, 2017.
2. Morelli A, Ertmer C, Westphal M, Rehberg S, Kampmeier T, Ligges S, Orecchioni A, D’Ippoliti F, Raffone C, Venditti M, et al. Effect of heart rate control with esmolol on hemodynamic and clinical outcomes in patients with septic shock: a randomized clinical trial. JAMA 310 16: 1683–1691, 2013.
3. Hutcheon DE, Vincent ME, Sandhu RS. Renal electrolyte excretion pattern in response to bumetanide in healthy volunteers. J Clin Pharmacol 21 (11–12 pt 2):604–609, 1981.
4. Atkinson TM, Ohman EM, O’Neill WW, Rab T, Cigarroa JE. A practical approach to mechanical circulatory support in patients undergoing percutaneous coronary intervention. An interventional perspective. JACC Cardiovasc Interv 9 9: 871–873, 2016.
5. Mekontso-Dessap A, Castelain V, Anguel N, Bahloul M, Schauvliege F, Richard C, Teboul JL. Combination of venoarterial PCO2 difference with arteriovenous O2 content difference to detect anaerobic metabolism in patients. Intensive Care Med 28 3: 272–277, 2002.
6. Mallat J, Lemyze M, Meddour M, Pepy F, Gasan G, Barrailler S, Durville E, Temime J, Vangrunderbeeck N, Tronchon L, et al. Ratios of central venous-to-arterial carbon dioxide content or tension to arteriovenous oxygen content are better markers of global anaerobic metabolism than lactate in septic shock patients. Ann Intensive Care 6: 10–18, 2016.
7. Lim HS. The effect of Impella CP on cardiopulmonary physiology during venoarterial extracorporeal membrane oxygenation support. Artif Organs 41 12: 1109–1112, 2017.
8. Wernovsky G, Wypij D, Jonas RA, Mayer JE Jr, Hanley FL, Hickey PR, Walsh AZ, Chang AC, Castaneda AR, Newburger JW, et al. Postoperative course and hemodynamic profile after the arterial switch operation in neonates and infants. A comparison of low-flow cardiopulmonary bypass and circulatory arrest. Circulation 92 8: 2226–2235, 1995.
9. Lim HS, Zaphiriou A. Sodium nitroprusside in patients with mixed pulmonary hypertension and left heart disease: hemodynamic predictors of response and prognostic implications. J Card Fail 22 2: 117–124, 2016.
10. Fincke R, Hochman JS, Lowe AM, Menon V, Slater JM, Webb JG, LeJemtel TH. Cotter G SHOCK Investigators. Cardiac power is the strongest hemodynamic correlated of mortality in cardiogenic shock: a report from the SHOCK Trial Registry. J Am Coll Cardiol 44 2: 340–348, 2004.
11. Severinghaus JW. Simple, accurate equations for human blood oxygen dissociation computations. J Appl Physiol 46 3: 599–602, 1979.
12. Teboul JL, Scheeren T. Understanding the Haldane effect. Intensive Care Med 43 1: 91–93, 2017.
13. Jakob SM, Groeneveld ABJ, Teboul JL. Venous–arterial CO2 to arterial–venous O2 difference ratio as a resuscitation target in shock states? Intensive Care Med 41 5: 936–938, 2015.
14. Dres M, Monnet X, Teboul JL. Hemodynamic management of cardiovascular failure by using PCO2 venous-arterial difference. J Clin Monit Comput 26 5: 367–374, 2012.
15. Gilfix BM, Bique M, Magder S. A physical chemical approach to the analysis of acid-base balance in the clinical setting. J Crit Care 8 4: 187–197, 1993.
16. Fencl V, Leith DE. Stewart's quantitative acid-base chemistry: applications in biology and medicine. Respir Physiol 91 1: 1–16, 1993.
17. Ezekowitz JA, McAlister FA, Armstrong PW. Anemia is common in heart failure and is associated with poor outcomes: insights from a cohort of 12 065 patients with new-onset heart failure. Circulation 107 2: 223–225, 2003.
18. Androne AS, Katz SD, Lund L, LaManca J, Hudaihed A, Hryniewicz K, Mancini DM. Hemodilution is common in patients with advanced heart failure. Circulation 107 2: 226–229, 2003.
19. Ishani A, Weinhandl E, Zhao Z, Gilbertson DT, Collins AJ, Yusuf S, Herzog CA. Angiotensin-converting enzyme inhibitor as a risk factor for the development of anemia, and the impact of incident anemia on mortality in patients with left ventricular dysfunction. J Am Coll Cardiol 45 3: 391–399, 2005.
20. Mrug M, Stopka T, Julian BA, Prchal JF, Prchal JT. Angiotensin II stimulates proliferation of normal early erythroid progenitors. J Clin Invest 100 9: 2310–2314, 1997.
21. Dries DL, Exner DV, Domanski MJ, Greenberg B, Stevenson LW. The prognostic implications of renal insufficiency in asymptomatic and symptomatic patients with left ventricular systolic dysfunction. J Am Coll Cardiol 35 3: 681–689, 2000.
22. Rauchhaus M, Doehner W, Francis DP, Davos C, Kemp M, Liebenthal C, Niebauer J, Hooper J, Volk HD, Coats AJ, et al. Plasma cytokine parameters and mortality in patients with chronic heart failure. Circulation 102 25: 3060–3067, 2000.
23. Iversen PO, Woldbaek PR, Tonnessen T, Christensen G. Decreased hematopoiesis in bone marrow of mice with congestive heart failure. Am J Physiol Regul Integr Comp Physiol 282 1:R166–172, 2002.
24. Metcalfe J, Dhindsa DS, Edwards MJ, Mourdjinis A. Decreased affinity of blood for oxygen in patients with low-output heart failure. Circ Res 25 1: 47–51, 1969.
25. Bersin RM, Kwasman M, Lau D, Klinski C, Tanaka K, Khorrami P, DeMarco T, Wolfe C, Chatterjee K. Importance of oxygen-hemoglobin binding to oxygen transport in congestive heart failure. Br Heart J 70 5: 443–447, 1993.
26. Vallet B, Teboul JL, Cain S, Curtis S. Venoarterial CO2 difference during regional ischemic or hypoxic hypoxia. J Appl Physiol 89 4: 1317–1321, 2000.
27. Mallat J, Lemyze M, Meddour M, Pepy F, Gasan G, Barrailler S, Durville E, Temime J, Vangrunderbeeck N, Tronchon L, et al. Ratios of central venous-to-arterial carbon dioxide content or tension to arteriovenous oxygen content are better markers of global anaerobic metabolism than lactate in septic shock patients. Ann Intensive Care 6 1: 10–18, 2016.
28. Garcia-Alvarez M, Marik P, Bellomo R. Stress hyperlactataemia: present understanding and controversy. Lancet Diabetes Endocrinol 2 4: 339–347, 2014.
29. James JH, Luchette FA, McCarter FD, Fischer JE. Lactate is an unreliable indicator of tissue hypoxia in injury or sepsis. Lancet 345 9177: 505–508, 1999.
30. Grodin JL, Simon J, Hachamovitch R, Wu Y, Jackson G, Halkar M, Starling RC, Testani JM, Tang WH. Prognostic role of serum chloride levels in acute decompensated heart failure. J Am Coll Cardiol 66 6: 659–666, 2015.
31. Grodin JL, Verbrugge FH, Ellis SG, Mullens W, Testani JM, Tang WH. Importance of abnormal chloride homeostasis in stable chronic heart failure. Circ Heart Fail 9 1:e002453, 2016.
32. Lorenz JN, Kotchen TA, Ott CE. Effect of Na and Cl infusion on loop function and plasma renin activity in rats. Am J Physiol 258 (5 pt 2):F1328–F1335, 1990.
33. Ponce-Coria J, San-Cristobal P, Kahle KT, Vazquez N, Pacheco-Alvarez D, de Los Heros P, Juárez P, Muñoz E, Michel G, Bobadilla NA, et al. Regulation of NKCC2 by a chloride-sensing mechanism involving the WNK3 and SPAK kinases. Proc Natl Acad Sci USA 105 24: 8458–8463, 2008.
34. Schrier RW, Abraham WT. Hormones and hemodynamics in heart failure. N Engl J Med 341 8: 577–585, 1999.
35. Ellison DH. The physiologic basis of diuretic synergism: its role in treating diuretic resistance. Ann Intern Med 114 10: 886–894, 1991.
36. Musa T, Chue C, Lim HS. Mechanical circulatory support for decompensated heart failure. Curr Heart Fail Rep 14 5: 365–375, 2017.
37. Jeger RV, Lowe AM, Buller CE, Pfisterer ME, Dzavik V, Webb JG, Hochman JS, Jorde UP. Investigators SHOCK. Hemodynamic parameters are prognostically important in cardiogenic shock but similar following early revascularization or initial medical stabilization: a report from the SHOCK trial. Chest 132 6: 1794–1803, 2007.
Keywords:

Cardiogenic shock; heart failure; mechanical circulatory support

© 2018 by the Shock Society