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.).

Venoarterial extracorporeal membrane oxygenation is a viable option as a bridge to heart transplant.

OBJECTIVE: Venoarterial extracorporeal membrane oxygenation is a rescue therapy for patients in cardiogenic shock. We hypothesize that patients bridged to heart transplant with extracorporeal membrane oxygenation have decreased survival. METHODS: The United Network of Organ Sharing database was retrospectively reviewed from January 1, 1999, to March 31, 2018, for heart transplant recipients. Recipients bridged with any form of mechanical support and those without support were compared with recipients bridged with extracorporeal membrane oxygenation. The primary end point was restricted mean survival time through 16.7 years. RESULTS: Of 26,918 recipients, 15,076 required no pretransplant mechanical support (56.0%). Support patients included 9321 with left ventricular assist devices (34.6%), 53 with right ventricular assist devices (0.2%), 258 with total artificial hearts (1.0%), 686 with biventricular assist devices (2.6%), 1378 with intra-aortic balloon pumps (5.1%), and 146 who required extracorporeal membrane oxygenation (0.5%). In the first 16.7 years post-transplant, compared with recipients bridged with extracorporeal membrane oxygenation, estimated adjusted restricted mean survival time was higher in patients who required no mechanical support (16.6 months [14.0-19.4]) and patients with a left ventricular assist device (16.5 months [99% confidence interval, 13.9-19.2]), an intra-aortic balloon pump (11.2 months [8.3-14.7]), or a biventricular assist device (6.6 months [3.6-10.3]). Restricted mean survival time in patients with a right ventricular assist device or a total artificial heart was similar to patients with extracorporeal membrane oxygenation. CONCLUSIONS: Recipients bridged with extracorporeal membrane oxygenation were estimated to survive 16.6 months less than nonmechanical circulatory support recipients. Bridge to heart transplant with extracorporeal membrane oxygenation is a viable option, and these patients should be considered transplant candidates.

Matrix-Degrading Enzyme Expression and Aortic Fibrosis During Continuous-Flow Left Ventricular Mechanical Support.

BACKGROUND: The effects of nonphysiological flow generated by continuous-flow (CF) left ventricular assist devices (LVADs) on the aorta remain poorly understood. OBJECTIVES: The authors sought to quantify indexes of fibrosis and determine the molecular signature of post-CF-LVAD vascular remodeling. METHODS: Paired aortic tissue was collected at CF-LVAD implant and subsequently at transplant from 22 patients. Aortic wall morphometry and fibrillar collagen content (a measure of fibrosis) was quantified. In addition, whole-transcriptome profiling by RNA sequencing and follow-up immunohistochemistry were performed to evaluate CF-LVAD-mediated changes in aortic mRNA and protein expression. RESULTS: The mean age was 52 ± 12 years, with a mean duration of CF-LVAD of 224 ± 193 days (range 45-798 days). There was a significant increase in the thickness of the collagen-rich adventitial layer from 218 ± 110 µm pre-LVAD to 410 ± 209 µm post-LVAD (P < 0.01). Furthermore, there was an increase in intimal and medial mean fibrillar collagen intensity from 22 ± 11 a.u. pre-LVAD to 41 ± 24 a.u. post-LVAD (P < 0.0001). The magnitude of this increase in fibrosis was greater among patients with longer durations of CF-LVAD support. CF-LVAD led to profound down-regulation in expression of extracellular matrix-degrading enzymes, such as matrix metalloproteinase-19 and ADAMTS4, whereas no evidence of fibroblast activation was noted. CONCLUSIONS: There is aortic remodeling and fibrosis after CF-LVAD that correlates with the duration of support. This fibrosis is due, at least in part, to suppression of extracellular matrix-degrading enzyme expression. Further research is needed to examine the contribution of nonphysiological flow patterns on vascular function and whether modulation of pulsatility may improve vascular remodeling and long-term outcomes.

Advanced heart failure patients supported with ambulatory inotropic therapy: What defines success of therapy?

OBJECTIVE: The objective of this study was to describe the profiles and outcomes of a cohort of advanced heart failure patients on ambulatory inotropic therapy (AIT). BACKGROUND: With the growing burden of patients with end-stage heart failure, AIT is an increasingly common short or long-term option, for use as bridge to heart transplant (BTT), bridge to ventricular assist device (BTVAD), bridge to decision regarding advanced therapies (BTD) or as palliative care. AIT may be preferred by some patients and physicians to facilitate hospital discharge. However, counseling patients on risks and benefits is critically important in the modern era of defibrillators, durable mechanical support and palliative care. METHODS: We retrospectively studied a cohort of 241 patients on AIT. End points included transplant, VAD implantation, weaning of inotropes, or death. The primary outcomes were survival on AIT and ability to reach intended goal if planned as BTT or BTVAD. We also evaluated recurrent heart failure hospitalizations, incidence of ventricular arrhythmias (VT/VF) and indwelling line infections. Unintended consequences of AIT, such reaching unintended end point (e.g. VAD implantation in BTT patient) or worse than expected outcome after LVAD or HT, were recorded. RESULTS: Mean age of the cohort was 60.7 ± 13.2 years, 71% male, with Class III-IV heart failure (56% non-ischemic). Average ejection fraction was 19.4 ± 10.2%, pre-AIT cardiac index was 1.5 ± 0.4 L/min/m2 and 24% had prior ventricular arrhythmias. Overall on-AIT 1-year survival was 83%. Hospitalizations occurred in 51.9% (125) of patients a total of 174 times for worsening heart failure, line complication or ventricular arrhythmia. In the BTT cohort, only 42% were transplanted by the end of follow-up, with a 14.8% risk of death or delisting for clinical deterioration. For the patients who were transplanted, 1-year post HT survival was 96.7%. In the BTVAD cohort, 1-year survival after LVAD was 90%, but with 61.7% of patients undergoing LVAD as INTERMACS 1-2. In the palliative care cohort, only 24.5% of patients had a formal palliative care consult prior to AIT. CONCLUSIONS: AIT is a strategy to discharge advanced heart failure patients from the hospital. It may be useful as bridge to transplant or ventricular assist device, but may be limited by complications such as hospitalizations, infections, and ventricular arrhythmias. Of particular note, it appears more challenging to bridge to transplant on AIT in the new allocation system. It is important to clarify the goals of AIT therapy upfront and continue to counsel patients on risks and benefits of the therapy itself and potential unintended consequences. Formalized, multi-disciplinary care planning is essential to clearly define individualized patient, as well as programmatic goals of AIT.

Predicting post-LVAD outcome: Is there a role for cognition?

BACKGROUND: Cognition has been found to influence risk of stroke and death for a variety of patient groups but this association has not been examined in heart failure (HF) patients undergoing left ventricular assist device (LVAD) implant. We aimed to study the relationship between cognition, stroke, and death in a cohort of patients who received LVAD therapy. It was hypothesized that cognitive test results obtained prior to LVAD placement would predict stroke and death after surgery. METHODS: We retrospectively identified 59 HF patients who had cognitive assessment prior to LVAD placement. Cognitive assessment included measures of attention, memory, language, and visualmotor speed and were averaged to produce one z-score variable per patient. Survival analyses, censored for transplant, evaluated predictors for stroke and death within a follow-up period of 900 days. RESULTS: For patients with stroke or death during the follow up period, the average cognitive z-score predicted post-LVAD stroke (HR = 0.513, 95% CI = 0.31-0.86, p = 0.012) and death (HR = 0.166, 95% CI = 0.06-0.47, p = 0.001). Cognitive performances were worse in the patients who suffered stroke or died. No other variable predicted stroke and death within the follow up period when the cognitive variable was in the model. CONCLUSION: Cognitive performance was predictive of post-LVAD risk of stroke and death. Results are consistent with findings from other studies in non-LVAD samples and may reflect early signs of neurologic vulnerability. Further studies are needed to clarify the relationship between cognition and LVAD outcomes in order to optimize patient selection, management, and advanced care planning.

Association between splenic volume and pulsatility index in patients with left ventricular assist devices.

The spleen serves as a blood volume reservoir for systemic volume regulation in heart failure (HF) patients. Changes are seen in spleen size in advanced HF patients after left ventricular assist device (LVAD) implantation. The pulsatility index (PI) is an indicator of native heart contractility with hemodynamic changes in patients using LVAD. We hypothesized that the splenic volume was associated with the PI, reflecting the hemodynamics in advanced HF patients with LVADs. Herein, we investigated the relationship between splenic volume and PI in these patients. Forty-four patients with advanced HF underwent implantation of HeartMate II® (Abbott, Chicago, IL, USA) as a bridge to heart transplantation at the Nagoya University Hospital between October 2013 and June 2019. The data of 27 patients (21 men, median age 46 years) were analyzed retrospectively. All patients underwent blood tests, echocardiography, right heart catheterization, and computed tomography (CT). Spleen size was measured via CT volumetry; the splenic volume (median: 190 mL) correlated with right arterial pressure (r = 0.431, p = 0.025) and pulmonary capillary wedge pressure (r = 0.384, p = 0.048). On multivariate linear regression analysis, the heart rate (ß = -0.452, p = 0.003), pump power (ß = -0.325, p = 0.023), and splenic volume (ß = 0.299, p = 0.038) were independent determinants of PI. The splenic volume was associated with PI, reflecting the cardiac preload in advanced HF patients with LVADs. Thus, spleen measurement using CT may help estimate the systemic volume status and understand the hemodynamic conditions in LVAD patients.

Bridge to heart transplantation in patients with cardiogenic shock: a 20-year experience with two different surgical strategies.

AIMS: We aimed to describe how treatment of patients in cardiogenic shock bridged to heart transplantation with mechanical circulatory support, using either biventricular assist devices (BVADs) or extracorporeal life support (ECLS), has evolved in the last 20 years in our centre. METHODS: Since 1998, 72 patients with refractory heart failure and indication for heart transplantation have received mechanical circulatory support: 40 had an ECLS system and 32 a BVAD. RESULTS: Early mortality was similar (17.5 vs. 9.4%, P = 0.25) regardless of the type of support. After a median support time of 8 (1-27) vs. 34 (0-385) days (P < 0.01), 70 vs. 65.6% (P = 0.69) of patients underwent transplantation in the two groups. Prior to transplantation, BVAD patients were more stable with lower need for mechanical ventilation (9 vs. 57%, P < 0.01) and dialysis (0 vs. 38%, P < 0.01). Thirty-day mortality after transplantation was similar (18 vs. 14%, P = 0.53). Patients with extracorporeal support had higher rates of renal (P = 0.02) and respiratory failure (P = 0.03), infections (P = 0.02), atrial fibrillation (P = 0.03) and longer ICU stay (P = 0.01). Late survival was similar, while 5-year freedom from coronary vasculopathy was higher in those with BVAD (P = 0.03). CONCLUSION: Although ECLS provides faster and simpler assistance compared with BVADs, no differences in early and medium-term outcomes in the last 20 years were observed in patients with cardiogenic shock. However, BVADs provided longer duration of support, better multiorgan recovery allowing more adequate graft selection, resulting in a lower rate of posttransplant complications.

Practical Management of ECPELLA.

Veno-arterial extracorporeal membrane oxygenation (ECMO) is a strong mechanical circulatory device for patients with hemodynamic deterioration due to cardiogenic shock, but its drawback is an increase in left ventricular afterload. The Impella axial-flow transcatheter left ventricular assist device is a recently developed promising device to mechanically unload the left ventricle, although its support flow may not necessarily be sufficient to support shock vital. Recently, ECMO and concomitant Impella support (ECPELLA) is increasingly being used to treat cardiogenic shock by maintaining systemic circulation and unloading the left ventricle. There are several pitfalls to maintaining ECPELLA, and one useful tool is the pulmonary artery pulsatility index. The clinical advantages of ECPELLA compared to conventional ECMO alone should be demonstrated in larger scale studies in the near future.

Serially Measured Cytokines and Cytokine Receptors in Relation to Clinical Outcome in Patients With Stable Heart Failure.

In this prospective cohort study of 250 stable heart failure patients with trimonthly blood sampling, we investigated associations of 17 repeatedly measured cytokines and cytokine receptors with clinical outcome during a median follow-up of 2.2 (25th-75th percentile, 1.4-2.5) years. Sixty-six patients reached the primary end point (composite of cardiovascular mortality, heart failure hospitalization, heart transplantation, left ventricular assist device implantation). Repeatedly measured levels of 8 biomarkers correlated with clinical outcomes independent of clinical characteristics. Rates of change over time (slopes of biomarker evolutions) remained independently associated with outcome for 15 biomarkers. Thus, temporal patterns of cytokines and cytokine receptors, in particular tumour necrosis factor ligand superfamily member 13B and interleukin-1 receptor type 1, might contribute to personalized risk assessment.

A Case of TAVR Complicated by Severe Functional Mitral Regurgitation.

Mitral regurgitation (MR) is a known complication of transcatheter aortic valve replacement (TAVR). We report a case of a 90-year-old man with severe symptomatic aortic stenosis who underwent elective TAVR. The procedure was complicated by severe functional MR from left ventricular stunning and dilatation caused by hypotension throughout the procedure. An Impella CP (Abiomed, Inc, Danvers, MA) was inserted to unload the left ventricle and decrease its size with subsequent improvement in MR severity, which was sustained after Impella CP removal. In conclusion, we present the first case of successful management of post-TAVR severe functional MR with an Impella CP.

Don't Drive Blind: Driving Pressure to Optimize Ventilator Management in ECMO.

INTRODUCTION: Driving pressure (DP) while on ECMO has been studied in acute respiratory distress syndrome (ARDS) but no studies exist in those on ECMO without ARDS. We aimed to study association of mortality with DP in all patients on ECMO and compare change in DP before and after initiation of ECMO. METHODS: Consecutive patients placed on ECMO either veno-arterial ECMO or veno-venous ECMO between August 2010 and February 2017 were reviewed. The outcomes were compared based on DP before and after ECMO initiation. RESULTS: A total of 192 patients were included: 68 (35%) had ARDS while 124 (65%) did not. There were 70 individuals for whom DP was available, 33 (47%) had a decrease in DP, whereas 32 (46%) had an increase in DP and 5 (7%) had no change in DP after ECMO initiation. Those with an increase in DP had a higher initial PEEP (14 vs 9 cm H2O, p < 0.001) and a higher PEEP decrease after ECMO (6.4 cm H2O vs by 2.5 cm H2O, p < 0.001). Those with an increase in DP had a significantly longer stay on ECMO than those without (p = 0.022). On multivariable analysis, higher DP 24 h after ECMO initiation was associated with an increase in 30-day mortality (OR 1.15, 75% CI 1.07-1.24, p ≤ 0.001). CONCLUSION: A significant proportion of patients experienced an increase in driving pressure and decrease in compliance after initiation of ECMO. Higher driving pressure after initiation of ECMO is associated with increased adjusted 30-day mortality. Individualized ventilator strategies are needed to reduce mechanical stress while on ECMO.

How to Manage Temporary Mechanical Circulatory Support Devices in the Critical Care Setting: Translating Physiology to the Bedside.

The incidence of cardiogenic shock and the utilization of mechanical circulatory support devices are increasing in the US. In this review we discuss the pathophysiology of cardiogenic shock through basic hemodynamic and myocardial energetic principles. We also explore the commonly used platforms for temporary mechanical circulatory support, their advantages, disadvantages and practical considerations relating to implementation and management. It is through the translation of underlying physiological principles that we can attempt to maximize the clinical utility of circulatory support devices and improve outcomes in cardiogenic shock.

The Total Artificial Heart: Where Are We?

The total artificial heart (TAH) is a device that replaces the failing ventricles. There have been numerous TAHs designed over the last few decades, but the one with the largest patient experience is the SynCardia temporary TAH. The 50-mL and 70-mL sizes have been approved in the United States, Europe, and Canada as a bridge to transplantation. It is indicated in patients with severe biventricular failure or structural heart issues that preclude the use of a left ventricular assist device. The majority of the patients implanted are Interagency Registry for Mechanically Assisted Circulatory Support profile 1 or 2. The 1-year survival in experienced centers that have implanted over 10 TAHs is 73%. The risk factors for death include older age, need for preimplantation dialysis, and malnutrition. The most common causes of death are multiple organ failure, usually the result of physiologic deterioration before implantation, and neurologic dysfunction. The device allows the patient to be discharged home and managed as an outpatient. Proper patient selection, the timing of intervention, patient care, and device management are essential for a suitable outcome. In addition, the CARMAT TAH is another device that will soon be studied in a clinical trial in the United States. The BiVACOR TAH is a revolutionary design utilizing electromagnetic levitation that is expected to enter a clinical trial in the next few years.

How to Bail Out Patients with Severe Acute Myocardial Infarction.

Cardiogenic shock (CS) is the most serious complication of acute myocardial infarction (AMI). The practice of early revascularization by percutaneous coronary intervention, and advances in pharmacotherapy have reduced the rate of complications of CS. However, when CS is combined with AMI, mortality from AMI is still high, and many clinicians are wondering how to treat CS with AMI. In recent years, mechanical circulatory support (MCS) devices have improved the clinical outcome in AMI patients with CS. For best outcome, treatment of AMI with CS should always consider treatments that improve the prognosis of the patients.

Acute Decompensated Heart Failure in Patients with Heart Failure with Reduced Ejection Fraction.

Acute decompensated heart failure (ADHF) requires immediate treatments because it impairs perfusion to systemic organs and their function. Half of all patients with ADHF are diagnosed with heart failure with reduced left ventricular ejection fraction (HFrEF). The initial goal of management for ADHF is to stabilize hemodynamic status. Pulmonary edema is treated with vasodilators or diuretics. Inhibitors of the renin-angiotensin-aldosterone system and ß-blockers should be started and/or increased to meet the maximum dose, ideally the target dose, that the patient can tolerate as a treatment of HFrEF. Patients with severe circulatory failure need inotropic drugs or mechanical circulatory support.

Contemporary Management of Acute Decompensated Heart Failure and Cardiogenic Shock.

Cardiogenic shock (CS) is a life-threatening condition characterized by end-organ hypoperfusion and hypoxia primarily due to cardiac dysfunction and low cardiac output. Unfortunately, the mortality and morbidity associated with CS have remained high despite notable advances in heart failure management. Treatment should be carefully guided by hemodynamics assessment. Although inotropes, vasopressors, mechanical circulatory support, and catheter intervention for critical valve lesion are not always recommended, they are helpful in selected patients. Early diagnosis, accurate hemodynamic assessment, and prompt therapeutic intervention are crucial in the management of acute decompensated heart failure with CS.

Non-invasive assessment of arterial pulsatility in patients with continuous-flow left ventricular assist devices.

INTRODUCTION: Long-term use of continuous-flow left ventricular assist devices may have negative consequences for autonomic, cardiovascular and gastrointestinal function. It has thus been suggested that non-invasive monitoring of arterial pulsatility in patients with a left ventricular assist device is highly important for ensuring patient safety and longevity. We have developed a novel, semi-automated frequency-domain-based index of arterial pulsatility that is obtained during suprasystolic occlusions of the upper arm: the 'cuff pulsatility index'. PURPOSE: The purpose of this study was to evaluate the relationship between the cuff pulsatility index and invasively determined arterial pulsatility in patients with a left ventricular assist device. METHODS: Twenty-three patients with a left ventricular assist device with end-stage heart failure (six females: age = 65 ± 9 years; body mass index = 30.5 ± 3.7 kg m-2) were recruited for this study. Suprasystolic occlusions were performed on the upper arm of the patient's dominant side, from which the cuff pressure waveform was obtained. Arterial blood pressure was obtained from the radial artery on the contralateral arm. Measurements were obtained in triplicate. The relationship between the cuff pressure and arterial blood pressure waveforms was assessed in the frequency-domain using coherence analysis. A mixed-effects approach was used to assess the relationship between cuff pulsatility index and invasively determined arterial pulsatility (i.e. pulse pressure). RESULTS: The cuff pressure and arterial blood pressure waveforms demonstrated a high coherence up to the fifth harmonic of the cardiac frequency (heart rate). The cuff pulsatility index accurately tracked changes in arterial pulse pressure within a given patient across repeated measurements. CONCLUSIONS: The cuff pulsatility index shows promise as a non-invasive index for monitoring residual arterial pulsatility in patients with a left ventricular assist device across time.

Haemodynamic evaluation of the new pulsatile-flow generation method in vitro.

Continuous-flow ventricular-assist devices are widely used to support patients with advanced heart failure, because continuous-flow ventricular-assist devices are more durable, have smaller sizes and have better survival rates for patients compared to the pulsatile-flow ventricular-assist devices. Nevertheless, continuous-flow ventricular-assist devices often cause complications such as gastrointestinal bleeding, haemorrhagic stroke, and aortic insufficiency and have a negative impact on the microcirculation for both long-time implantable and short-time extracorporeal systems. The aim of this study is the evaluation of the pulsatile-flow generation method in continuous-flow ventricular-assist device without pump speed changes. The method may be used for short-time extracorporeal continuous-flow mechanical circulatory support and long-time implantable mechanical circulatory support. A shunt with a controlled adjustable valve, that clamps periodically, is connected in parallel to the continuous-flow ventricular-assist device. We compared the continuous-flow ventricular-assist device operating with and without the shunt on the mock circulation loop. The continuous-flow ventricular-assist device-shunt system was connected according to the left ventricle-aorta circuit and worked in phase with the ventricle. Heart failure was simulated on the mock circulation circuit. Rotaflow (Maquet Inc.) was used as the continuous-flow pump. Haemolysis studies of the system for generating a pulse flow were carried out at a flow rate of 5 L/min and a pressure drop of 100 mm Hg. To compare the haemodynamic efficiency, we used the aortic pulsation index Ip, the equivalent energy pressure and the surplus haemodynamic energy. These indexes were higher in the pulsatile mode (Ip - 4 times, equivalent energy pressure by 7.36% and surplus haemodynamic energy - 10 times), while haemolysis was the same. The normalised index of haemolysis was 0.0015 ± 0.001. The results demonstrate the efficiency of the pulsatile-flow generation method for continuous-flow ventricular-assist devices without impeller rotation rate changes.