Does glucagon have a positive inotropic effect in the human heart?

Glucagon is considered to exert cardiostimulant effects, most notably the enhancement of heart rate and contractility, due to the stimulation of glucagon receptors associated with Gs protein stimulation which causes adenylyl cyclase activation and the consequent increase in 3′,5′-cyclic adenosine monophosphate production in the myocardium. These effects have been extensively demonstrated in experimental studies in different animal species. However, efforts to extrapolate the experimental data to patients with low cardiac output states, such as acute heart failure or cardiogenic shock, have been disappointing. The experimental and clinical data on the cardiac effects of glucagon are described here.     

Emergency aorto-coronary venous bypass graft in cardiogenic shock

The mortality rate of shock complicating myocardial infarction is extremely high (80-100%) despite intensive medical management. Five patients with acute myocardial infarction and cardiogenic shock received an emergency aorto-coronary bypass graft, from three hours to five days after the onset of infarction and three to nine hours after the onset of shock. Selective coronary angiography was performed in all cases prior to operation. Four of the five patients survived and were discharged from hospital. Two cases with A-V dissociation and complete heart block reverted to normal sinus rhythm after the operation. This limited experience indicates that emergency aortocoronary bypass graft surgery can reduce mortality significantly in properly selected cases of cardiogenic shock.     

Shock Following Myocardial Infarction: A Clinical Survey of 140 Cases

All admissions for acute myocardial infarction to a metropolitan general hospital over a 10-year period have been reviewed. One hundred and forty patients developed complications meeting the criteria for cardiogenic shock. The mortality rate in this group of patients was 83%. The mortality rate in 95 patients who received treatment with intravenous noradrenaline was no different from that in 45 patients who did not receive this type of therapy (p = >0.8). Patients dying from cardiogenic shock were younger than those dying of other complications. Autopsy study of this group of shocked patients revealed a significantly lower incidence of previous healed myocardial infarction (p = <0.01).A decline in the annual incidence of cardiogenic shock was noted over the decade surveyed. It is suggested that this may be due to the earlier and more frequent use of intravenous noradrenaline. Despite the reduction in the incidence of shock, the annual mortality rate from myocardial infarction has remained unaltered.     

The acutely occluded left main coronary artery culprit in cardiogenic shock and initial percutaneous coronary intervention: a substudy of the Manitoba "no option" left main PCI registry

We aim to describe the in-hospital outcomes of the first reported Canadian cohort of patients with cardiogenic shock and acute myocardial infarction (MI) due to acute and total occlusion of the left main coronary artery, treated with initial percutaneous coronary intervention (PCI). Acute left main thromboses with cardiogenic shock were identified (N?= 8) from a retrospective consecutive cohort of high risk left main PCI (N?= 56) performed at our institution from 2004-2009. The mean age was 62.3?± 13.2?years, with 6 (75%) male patients. Successful PCI was performed in all patients, with thrombectomy utilized in 4 patients (50%), stenting in 7 patients (88%), and intra-aortic balloon pump augmentation in 7 patients (88%). Two patients (25%) required extracorporeal membrane oxygenation (ECMO) and 2 other patients required ventricular assist devices. Post-PCI coronary artery bypass grafting (CABG) was performed for 2 patients (25%). The mean SYNTAX score was 26.6?± 10.5. The mean logistic EuroSCORE was 30.4?± 12.6%. In-hospital mortality occurred in 3 patients (38%). Acute left main occlusion is a rare but devastating presentation of myocardial infarction, invariably with cardiogenic shock. Emergent PCI may be an effective method to acutely revascularize this subset of patients; however, aggressive post-PCI care including ECMO, CABG, and ventricular support may be required to improve patient survival.     

老年急性心肌梗死并心源性休克冠状动脉介入治疗的临床效果分析

目的:对比分析介入治疗和保守治疗对急性心梗合并心源性休克的老年患者的治疗效果。方法:回顾性分析急性心肌梗死并心源性休克患者,共入选230例,按照医生评估进行分组治疗,分为介入治疗组和非介入治疗组,介入组患者120例,接受冠脉介入治疗;非介入组患者110例,接受非介入治疗。对比分析危险因素以及治疗效果。结果:介入组中心肌梗死病史及心衰病史患者明显高于非介入组(24.2%vs 20%P<0.05;25%vs 17.3%,P<0.05),经皮冠状动脉介入治疗与非介入治疗相比能显著降低急性心梗合并心源性休克的老年患者住院病死率(40.8%vs 71.8%,P<0.05),非介入治疗组心律失常发生率高于介入治疗组(26.7%vs 21.8%,P<0.05),同时非介入治疗组肺部感染及肾衰的发病率较高(11.8%vs 5.8%P<0.05;8.2%vs 2.0%,P<0.05)。结论:针对急性心梗合并心源性休克的老年患者制定治疗方案时,虽然介入治疗存在更多的并发症,但是可以显著改善患者预后。     

Extracorporeal life support in cardiogenic shock: indications and management in current practice

Veno-arterial extracorporeal life support (VA-ECLS) provides circulatory and respiratory stabilisation in patients with severe refractory cardiogenic shock. Although randomised controlled trials are lacking, the use of VA-ECLS is increasing and observational studies repeatedly have shown treatment benefits in well-selected patients. Current clinical challenges in VA-ECLS relate to optimal management of the individual patient on extracorporeal support given its inherent complexity. In this review article we will discuss indications, daily clinical management and complications of VA-ECLS in cardiogenic shock refractory to conventional treatment strategies.     

The Effectiveness of Inodilators in Reducing Short Term Mortality among Patient with Severe Cardiogenic Shock: A Propensity-Based Analysis

Background

The best catecholamine regimen for cardiogenic shock has been poorly evaluated. When a vasopressor is required to treat patients with the most severe form of cardiogenic shock, whether inodilators should be added or whether inopressors can be used alone has not been established. The purpose of this study was to compare the impact of these two strategies on short-term mortality in patients with severe cardiogenic shocks.

Methods and Results

Three observational cohorts of patients with decompensated heart failure were pooled to comprise a total of 1,272 patients with cardiogenic shocks. Of these 1,272 patients, 988 were considered to be severe because they required a vasopressor during the first 24 hours. We developed a propensity-score (PS) model to predict the individual probability of receiving one of the two regimens (inopressors alone or a combination) conditionally on baseline-measured covariates. The benefit of the treatment regimen on the mortality rate was estimated by fitting a weighted Cox regression model. A total of 643 patients (65.1%) died within the first 30 days (inopressors alone: 293 (72.0%); inopressors and inodilators: 350 (60.0%)). After PS weighting, we observed that the use of an inopressor plus an inodilator was associated with an improved short-term mortality (HR: 0.66 [0.55–0.80]) compared to inopressors alone.

Conclusions

In the most severe forms of cardiogenic shock where a vasopressor is immediately required, adding an inodilator may improve short-term mortality. This result should be confirmed in a randomized, controlled trial.     

Statement of the ad hoc committee on the laboratory diagnosis of infectious and serum hepatitis.

A prospective study was carried out to determine the prognostic factors in patients with second-degree and complete heart block following acute myocardial infarction and to re-examine the indications for artificial transvenous pacing. Of the 117 consecutive patients with proved acute myocardial infarction, 15 developed advanced heart block (second degree and complete). The presence of the following factors, either alone or in combinations, were attended with poor prognosis: preceding Stokes-Adams syndrome, cardiogenic shock, congestive heart failure, complications secondary to cardiac arrest, anterior infarction and wide QRS complex. In the nine cases requiring artificial transvenous pacemaker because of Stokes-Adams attacks, congestive heart failure or frequent multifocal ventricular ectopic beats, there were five deaths. The remaining six patients, who were without complications and were not paced, all survived; these patients had normal QRS duration with heart rates above 60 per minute. This study indicates that prophylactic transvenous catheter insertion in acute heart block does not appear justified unless specific indication(s) arise. Postmortem studies revealed significant narrowing of all the major coronary vessels in all five fatalities. The overall mortality in this series of cases of acute heart block was 33%.     

Intra-Aortic Balloon Pump Counterpulsation during Primary Percutaneous Coronary Intervention for ST-Elevation Myocardial Infarction and Cardiogenic Shock: Insights from the British Columbia Cardiac Registry

Background

Cardiogenic shock complicating ST-elevation myocardial infarction (STEMI) is associated with significant morbidity and mortality. In the primary percutaneous coronary intervention (PPCI) era, randomized trials have not shown a survival benefit with intra-aortic balloon pump (IABP) therapy. This differs to observational data which show a detrimental effect, potentially reflecting bias and confounding. Without robust and valid risk adjustment, findings from non-randomized studies may remain biased.

Methods

We compared long-term mortality following IABP therapy in patients with cardiogenic shock undergoing PPCI during 2008–2013 from the British Columbia Cardiac Registry. We addressed measured and unmeasured confounding using propensity score and instrumental variable methods.

Results

A total of 12,105 patients with STEMI were treated with PPCI during the study period. Of these, 700 patients (5.8%) had cardiogenic shock. Of the patients with cardiogenic shock, 255 patients (36%) received IABP therapy. Multivariable analyses identified IABP therapy to be associated with increased mortality up to 3 years (HR = 1.67, 95% CI:1.20–2.67, p<0.001). This association was lost in propensity-matched analyses (HR = 1.23, 95% CI: 0.84–1.80, p = 0.288). When addressing measured and unmeasured confounders, instrumental variable analyses demonstrated that IABP therapy was not associated with mortality at 3 years (Δ = 16.7%, 95% CI: -12.7%, 46.1%, p = 0.281). Subgroup analyses demonstrated IABP was associated with increased mortality in non-diabetics; patients not undergoing multivessel intervention; patients without renal disease and patients not having received prior thrombolysis.

Conclusions

In this observational analysis of patients with STEMI and cardiogenic shock, when adjusting for confounding, IABP therapy had a neutral effect with no association with long-term mortality. These findings differ to previously reported observational studies, but are in keeping with randomized trial data.     

Intraaortic Balloon Pumping Assist Following Open Heart Surgery for Coronary Artery Disease

Intraaortic balloon pump (IABP) assist was employed in 36 patients after surgical operation for coronary artery disease. In 31 patients, the aid of IABP was required because cardiopulmonary bypass could not be terminated without it. In three of these patients, IABP assist was started before the surgical procedure because these patients were in cardiogenic shock due to myocardial infarction. In the remaining five patients, IABP assist was applied for refractory cardiogenic shock in the early postoperative period.The overall survival rate was 58 percent. IABP assist was used in 13 patients with an ejection fraction of 0.1 to 0.2 (normal 0.7). Nine of these patients survived.From our experience, it would appear that this temporary mechanical circulatory support provides a significant advantage in saving patients who might otherwise die after surgical procedures involving the coronary artery.     

Repairing a "broken heart" with hormone replacement therapy: case report of cardiogenic shock due to undiagnosed pituitary insufficiency

ObjectivesTo indicate cardiogenic shock as a very rare but serious clinical consequence of untreated panhypopituitarism attributable to Sheehan syndrome; to emphasize the importance of eliciting a detailed endocrine and obstetric history in women presenting with idiopathic heart failure; to highlight the diagnostic shortcomings of screening for thyroid dysfunction solely with thyroidstimulating hormone determinations; and to report the reversibility of severe heart failure induced by longterm pituitary insufficiency.MethodsDescribed is a case report of a 35yearold woman who presented with severe congestive heart failure, hypotension, and confusion. Her 2dimensional echocardiogram revealed appreciable systolic and diastolic dysfunction. In screening for possible endocrine causes of heart failure, a normal thyroidstimulating hormone level of 0.72 mIU/L (reference range, 0.35 to 5.5) was unremarkable; however, a profoundly low free thyroxine level of 0.12 ng/dL (reference range, 0.9 to 1.8) led clinicians to pursue a workup of central hypothyroidism.ResultsEndocrine testing confirmed the presence of panhypopituitarism and adrenal insufficiency. Magnetic resonance imaging of the brain revealed empty sella syndrome. Further questioning of the patient revealed a history of extensive postpartum bleeding 15 years earlier, failure to lactate, and secondary amenorrhea—all consistent with undiagnosed Sheehan syndrome. In the hospital, the patient was treated with intravenously administered corticosteroids and levothyroxine. Her mental status and symptomatic heart failure improved dramatically. After 9 months of oral levothyroxine and glucocorticoid therapy, the patient remained asymptomatic, and repeated echocardiography indicated completely normalized cardiac function.ConclusionSevere heart failure and cardiogenic shock can be a very rare (but fortunately reversible) complication of longstanding panhypopituitarism resulting from undiagnosed Sheehan syndrome. (Endocr Pract. 2012;18:e26e31)     

急性心肌梗死后血糖变化对预后的影响研究

目的：探讨急性心肌梗死后血糖变化对患者预后的影响。方法：对314例急性心肌梗死患者于入院后第2日早晨测空腹血糖值后,并进行回顾性对比分析。结果：随着血糖水平的逐渐升高,心力衰竭及心源性休克的发生率和病死率逐渐升高（P〈0.05）,严重心律失常的发生率逐渐升高,但差异无统计学意义（P〉0.05）。结论：急性心肌梗死患者伴应激性血糖升高者,随着血糖水平升高,其心力衰竭及心源性休克的发生率和病死率升高。血糖正常组预后明显好于血糖升高组。     

Effects of Phenoxybenzamine in Shock due to Myocardial Infarction

Treatment of cardiogenic shock with vasodilator drugs has been advocated on the basis of experimental work showing that a fall in peripheral resistance allows the cardiac output to increase without any increase in cardiac work.Seven patients suffering from shock secondary to myocardial infarction were treated with phenoxybenzamine. In two cases there was dramatic improvement in the signs and symptoms of shock, but in six of the seven cases there were severe adverse effects on respiration, including the development of wheezing and rales and rhonchi.     

Impaired Lignocaine metabolism in patients with myocardial infarction and cardiac failure.

Plasma concentrations of lignocaine were measured during and after infusion of lignocaine at 1.4 mg/min for 36-46 hours in 12 patients with myocardial infarction and one patient with cardiac failure due to uncontrolled ventricular tachycardia. In six patients without cardiac failure the plasma concentrations of lignocaine rose progressively during the infusion and the mean lignocaine half life was 4.3 hours compared with 1.4 hours in healthy subjects. Mean plasma lignocaine concentrations were significantly higher in seven patients with cardiac failure, and concentrations also rose during the infusion and the half life was considerably prolonged to 10.2 hours. Lignocaine concentrations rose rapidly to toxic levels when cardiogenic shock developed in one patient and did not fall when the infusion was stopped. The mean plasma antipyrine half life was moderately prolonged (19.4 hours) in a larger group of patients with myocardial infarction and cardiac failure but returned to normal during convalescence (13.2 hours). The metabolism of lignocaine is grossly abnormal in patients with cardiac failure and cardiogenic shock after myocardial infarction.     

The Acute Phase of Experimental Cardiogenic Shock Is Counteracted by Microcirculatory and Mitochondrial Adaptations

The mechanisms contributing to multiorgan dysfunction during cardiogenic shock are poorly understood. Our goal was to characterize the microcirculatory and mitochondrial responses following ≥10 hours of severe left ventricular failure and cardiogenic shock. We employed a closed-chest porcine model of cardiogenic shock induced by left coronary microembolization (n = 12) and a time-matched control group (n = 6). Hemodynamics and metabolism were measured hourly by intravascular pressure catheters, thermodilution, arterial and organ specific blood gases. Echocardiography and assessment of the sublingual microcirculation by sidestream darkfield imaging were performed at baseline, 2±1 and 13±3 (mean±SD) hours after coronary microembolization. Upon hemodynamic decompensation, cardiac, renal and hepatic mitochondria were isolated and evaluated by high-resolution respirometry. Low cardiac output, hypotension, oliguria and severe reductions in mixed-venous and hepatic O₂ saturations were evident in cardiogenic shock. The sublingual total and perfused vessel densities were fully preserved throughout the experiments. Cardiac mitochondrial respiration was unaltered, whereas state 2, 3 and 4 respiration of renal and hepatic mitochondria were increased in cardiogenic shock. Mitochondrial viability (RCR; state 3/state 4) and efficiency (ADP/O ratio) were unaffected. Our study demonstrates that the microcirculation is preserved in a porcine model of untreated cardiogenic shock despite vital organ hypoperfusion. Renal and hepatic mitochondrial respiration is upregulated, possibly through demand-related adaptations, and the endogenous shock response is thus compensatory and protective, even after several hours of global hypoperfusion.     

Inoperable aortic stenosis in the elderly: benefit from percutaneous transluminal valvuloplasty.

Eight patients with severe symptomatic calcific aortic stenosis were considered to be unsuitable for valve replacement. Four were admitted with pulmonary oedema and three in cardiogenic shock and one had angina at rest. With the use of echocardiographic and radiographic guidance percutaneous transluminal aortic valvuloplasty was carried out. Aortic gradients were reduced by an average of 40%. All four patients who presented with cardiac failure improved immediately and remained well six months later. The patient with angina was symptom free at nine months. Two of the three patients who presented in cardiogenic shock improved immediately and were well nine and three months later. The other patient died four hours after the procedure. Doppler echocardiographic studies showed a slight initial increase in aortic incompetence, but this did not worsen and valvar gradients remained improved three and six months later. Percutaneous valvuloplasty of the aortic valve is an effective therapeutic option in patients with severe calcific aortic stenosis who are unfit for surgery. Its role as an alternative to surgery has not been considered and should be investigated in a controlled clinical trial.     

Role of endothelins in septic,cardiogenic, and hemorrhagic shock

Shock is a condition where blood flow is inadequate for tissue needs. In all forms of shock, the concentrations of endothelins (ETs) are elevated, and they are especially high in septic shock. The rise in ETs plasma levels may initially have some positive homeostatic effects, for ETs can help restore normal vascular tone. However, high levels of ETs compromise the appropriate matching of flow to tissue needs and contribute to the pathophysiology of shock. Attempts at regulating the effects of ETs by the use of pharmacological blockers is made complicated by important interactions between the ETA and ETB receptors and potentially different effects on different tissues. We conclude that antagonism of ET receptors is unlikely to be helpful for cardiogenic or hemorrhagic shock. Furthermore, selective blockade is unlikely to be helpful. However, moderate doses of a mixed ET receptor antagonist may be of use for the management of septic patients.     

Assisted circulation following myocardial infarction: a review of 25 patients treated before 1971

Twenty-five patients with impending death from myocardial infarction were treated with assisted circulation. Of these, 19 had suffered cardiac arrest from which they could not be resuscitated and six were in severe, intractable and expectedly terminal cardiogenic shock.All patients were treated by venoarterial bypass employing a bubble oxygenator. Assistance was continued for an average duration of one hour and 45 minutes at a flow rate between two and four litres per minute. The patients all showed improved cerebral, pulmonary and renal function and acid-base values returned to normal.Five patients survived for at least one month and two were improved; hence 28% of these otherwise terminal patients were helped by this technique of assisted circulation.     

Hemodynamic monitoring in acute myocardial infarction.

The main cause of in-hospital death in patients with acute myocardial infarction is the "power failure syndrome". Hemodynamic monitoring provides precise and current data on the filling and output status of the left ventricle and, when indicated, the right ventricle. The information obtained is used to determine the hemodynamic status more precisely than is possible from conventional clinical assessment. It permits categorization of patients by hemodynamic status; the hemodynamic subset classification of Forrester, Diamond and Swan is a powerful tool in guiding therapy and establishing prognosis in individual patients. In addition to guiding the initiation of therapy, hemodynamic monitoring is useful in the continuing assessment of potent and complex treatment. This therapy is directed at resolving hemodynamic derangements without unfavourably altering the myocardial oxygen supply-demand relationship. Specific clinical indications for hemodynamic monitoring may include confusing or complicated clinical situations in which diagnostic problems exist, complicating mechanical derangements, severe congestive heart failure, cardiogenic shock and clinical research in acute myocardial infarction.     

Insertion of the Impella 5.0 left ventricular assist device via right anterior mini-thoracotomy: a novel practical approach

The Impella 5.0 microaxial pump is a miniaturized left ventricular assist device commonly used for circulatory support in acute cardiogenic shock. The catheter-based pump is designed to be inserted either into a peripheral artery or directly into the ascending aorta. We report the first case in which the Impella 5.0 device was placed directly into the ascending aorta via a small right anterior thoracotomy in a patient following acute myocardial infarction complicated by cardiogenic shock.