Burkhoff, D., Naidu, S. S.
Patients in a variety of cardiovascular disease states may benefit from temporary percutaneous cardiac support, including those in acute decompensated heart failure, fulminant myocarditis, acute myocardial infarction with or without cardiogenic shock and those undergoing high-risk percutaneous coronary intervention. The ideal percutaneous cardiac support device is safe, easy to use and versatile enough to meet the needs of various clinical situations and patient cohorts. In addition, it should provide maximal hemodynamic support and protection against myocardial ischemia. With these goals in mind, the scientific principles that govern hemodynamic effectiveness and myocardial protection as they pertain to acute support devices are reviewed.
Verma, S., Burkhoff, D., O’Neill, W. W.
The rate of performing primary percutaneous coronary intervention in patients with complex coronary artery disease is increasing. The use of percutaneous mechanical circulatory support devices provides critical periprocedural hemodynamic support. Mechanical support has increased the safety and efficacy of interventional procedures in this high-risk patient population. Predicting patient response to the selected intervention can be clinically challenging. Here we demonstrate a case where complete hemodynamic collapse during PCI was avoided by mechanical support provided by the Impella device. Further, we employ a comprehensive cardiovascular model to predict ventricular function and patient hemodynamics in response to the procedure. New computational tools may help interventionists visualize, understand, and predict the multifaceted hemodynamic aspects of these high risk procedures in individual patients.
Remmelink, M., Sjauw, K. D., Henriques, J. P., de Winter, R. J., Vis, M. M., Koch, K. T., Paulus, W. J., de Mol, B. A., Tijssen, J. G., Piek, J. J., Baan, J., Jr.
OBJECTIVES: We studied online left ventricular (LV) dynamic effects of mechanical LV unloading directly after percutaneous coronary intervention (PCI). BACKGROUND: Limited clinical information is available on the direct LV dynamic consequences of LV unloading in patients undergoing high-risk PCI and primary PCI for acute ST-elevation myocardial infarction. METHODS: The effects of the Impella LP2.5 device on LV dynamics were studied in 11 patients (elective high-risk PCI, n = 6; primary PCI, n = 5). LV pressure and volume were continuously assessed by a pressure-conductance catheter at 4 different support levels of the Impella, from 0 L/min at baseline to 2.5 L/min at maximal support. RESULTS: The response to increased LV unloading was not different between both groups of patients. The pooled data showed no change on global and systolic LV function during increased LV unloading, while diastolic function showed improvement as indicated by an increased LV compliance in all patients. There was a decrease in end-diastolic pressure from 22 +/- 12 to 13 +/- 9 mm Hg (P = 0.0001), in end-diastolic elastance from 0.134 +/- 0.060 to 0.091 +/- 0.064 mm Hg/mL (P = 0.009), and in end-diastolic wall stress from 84 +/- 50 to 47 +/- 39 mm Hg (P = 0.004). CONCLUSIONS: LV unloading decreases end-diastolic wall stress and improves diastolic compliance dose-dependently. Our results indicate beneficial LV unloading effects of Impella during high-risk and primary PCI.
Delepine, S., Furber, A. P., Beygui, F., Prunier, F., Balzer, P., Le Jeune, J. J., Geslin, P.
The goal of this study was to assess the regional variations of end-systolic wall stress in patients with reperfused Q wave acute myocardial infarction (AMI), with the use of a three-dimensional (3-D) approach. Fifteen normal volunteers and fifty patients with reperfused AMI underwent cardiac MRI that used a short-axis fast-gradient-echo sequence. The end-systolic wall stress was calculated with the use of the Grossman formula with the radius and the wall thickness defined with a 3-D approach using the tridimensional curvature. The mean wall stress was significantly increased at each level of the short-axis plane only in patients with anterior AMI. When calculated at a regional level in patients with anterior AMI, wall stress significantly increased in anterior sector as well as normal sector. In patients with inferior AMI, wall stress significantly increased only in inferior and lateral sectors. In conclusion, the quantification of regional wall stress by cardiac MRI is better with the 3D approach than other methods for precise evaluation in patients with AMI. Despite early reperfusion, the wall stress remained high in patients with anterior AMI.
Di Napoli, P., Taccardi, A. A., Grilli, A., Felaco, M., Balbone, A., Angelucci, D., Gallina, S., Calafiore, A. M., De Caterina, R., Barsotti, A.
BACKGROUND: Apoptosis has been implicated as a possible mechanism in the development of heart failure (HF), but the mechanisms involved remain unclear. In patients with severe dilated cardiomyopathy, we evaluated cardiomyocyte apoptosis in relation to the transmural distribution of Bax and Bcl-2 proteins (2 molecules inhibiting or promoting apoptosis, respectively) and left ventricular wall stresses. METHODS: We studied the presence and distribution of cardiomyocyte apoptosis in 90 tissue samples obtained from 8 patients who were undergoing left ventricular reduction with the Batista (ventricular remodeling) operation. Apoptosis was assessed in tissue samples taken from the entire left ventricular thickness (subdivided in subepicardial, midmyocardial, and subendocardial sections) with the terminal deoxynucleotidyl transferase mediated dUTP-biotin nick-end labeling (TUNEL) technique and DNA agarose gel electrophoresis. The expression of Bcl-2 and Bax proteins were determined with both Western analysis and immunohistochemistry. RESULTS: TUNEL-positive cells (apoptotic index) were 2.3% +/- 1.4%. Apoptotic cells were predominantly distributed in the subendocardium, where higher levels of Bax protein were detected. The ratio of Bax to Bcl-2 proteins (Bax/Bcl-2) was similar in the midmyocardium or subepicardium, but increased in the subendocardium, where it was directly related to systolic wall stress (y = 0.009x – 0.629; r2 = 0.85, P <.001). The apoptotic index was also directly related to systolic and end-diastolic stresses calculated from hemodynamic and echocardiographic data (r2 = 0.77, P <.001 and r2 = 0.40, P <.01, respectively). CONCLUSIONS: In patients with dilated cardiomyopathy, in whom cardiomyocyte apoptosis is an important cause of cell loss, apoptosis is more extensively localized in the subendocardium and strictly related to ventricular wall stresses and the Bax/Bcl-2 ratio.
Ezekowitz, J. A., Kaul, P., Bakal, J. A., Armstrong, P. W., Welsh, R. C., McAlister, F. A.
OBJECTIVES: The purpose of this study was to examine the long-term incidence of heart failure (HF) in elderly patients with myocardial infarction (MI). BACKGROUND: In-hospital HF is common after MI and is associated with poor short-term prognosis. Limited data exist concerning the long-term incidence or prognosis of HF after MI, particularly in the era of coronary revascularization. METHODS: A population-based cohort of 7,733 patients > or = 65 years of age hospitalized for a first MI (International Classification of Diseases-9th Revision-Clinical Modification code 410.x) and without a prior history of HF was established between 1994 and 2000 in Alberta, Canada, and followed up for 5 years. RESULTS: During the index MI hospitalization, 2,831 (37%) MI patients were diagnosed with new HF and 1,024 (13%) died. Among hospital survivors who did not have HF during their index hospitalization (n = 4,291), an additional 3,040 patients (71%) developed HF by 5 years, 64% of which occurred in the first year. In total, 5,871 (76%) elderly patients who survived their first MI developed HF over 5 years. Among those who survived the index hospitalization, the 5-year mortality rate was 39.1% for those with HF during the index MI hospitalization compared with 26.7% among those without HF (p < 0.0001) during the index MI hospitalization. Over the study period, the 5-year mortality rate after MI decreased by 28%, whereas the 5-year rate of HF increased by 25%. CONCLUSIONS: In this large cohort of elderly patients without a history of HF, HF developed in three-quarters in the 5 years after their first MI; this proportion increased over time as peri-MI mortality rates declined. New-onset HF significantly increases the mortality risk among these patients.
Patrick Horn, Malte Kelm, and Ralf Westenfeld
A 79-year-old woman was admitted in the emergency department as late comer in cardiogenic shock due to subacute nonST-elevation myocardial infarction, which clinically occurred 8 days prior. Coronary angiography depicted occlusion of a small circumflex artery. Revascularization was deemed unreasonable in the light of normal CK and elevated LDH/troponin serum levels. The patient was haemodynamically compromised with elevated lactate and imminent renal and liver failure. Acute Physiology and Chronic Health Evaluation (APACHE II) Score was 25 points corresponding to an in-hospital mortality of 51%. Percutaneous mechanical circulatory support (Impella CP) was implanted and haemodynamics stabilized over 48 h along with
Flaherty, M. P., Pant, S., Patel, S. V., Kilgore, T., Dassanayaka, S., Loughran, J. H., Rawasia, W., Dawn, B., Cheng, A., Bartoli, C. R.
Acute kidney injury (AKI) is common during high-risk percutaneous coronary intervention (PCI), particularly in those with severely reduced left ventricular ejection fraction. The impact of partial hemodynamic support with a microaxial percutaneous left ventricular assist device (pLVAD) on renal function after high-risk PCI remains unknown.
We tested the hypothesis that partial hemodynamic support with the Impella 2.5 microaxial pLVAD during high-risk PCI protected against AKI.
METHODS AND RESULTS:
In this retrospective, single-center study, we analyzed data from 230 patients (115 consecutive pLVAD-supported and 115 unsupported matched-controls) undergoing high-risk PCI with ejection fraction ≤35%. The primary outcome was incidence of in-hospital AKI according to AKI network criteria. Logistic regression analysis determined the predictors of AKI. Overall, 5.2% (6) of pLVAD-supported patients versus 27.8% (32) of unsupported control patients developed AKI (P<0.001). Similarly, 0.9% (1) versus 6.1% (7) required postprocedural hemodialysis (P<0.05). Microaxial pLVAD support during high-risk PCI was independently associated with a significant reduction in AKI (adjusted odds ratio, 0.13; 95% confidence intervals, 0.09-0.31; P<0.001). Despite preexisting CKD or a lower ejection fraction, pLVAD support protection against AKI persisted (adjusted odds ratio, 0.63; 95% confidence intervals, 0.25-0.83; P=0.04 and adjusted odds ratio, 0.16; 95% confidence intervals, 0.12-0.28; P<0.001, respectively).
Impella 2.5 (pLVAD) support protected against AKI during high-risk PCI. This renal protective effect persisted despite the presence of underlying CKD and decreasing ejection fraction.
WILLIAM W. O ’NEILL, THEODORE SCHREIBER, DAVID H. W. WOHNS, CHARANJIT RIHAL, SRIHARI S. NAIDU, ANDREW B. CIVITELLO, SIMON R. DIXON, JOSEPH M. MASSARO, BRIJESHWAR MAINI, E. MAGNUS OHMAN
Prompt revascularization with percutaneous coronary intervention (PCI) has signiﬁcantly reduced the incidence of cardiogenic shock (CS) and improved survival in the setting of acute myocardial infarction (AMI).1,2 However, when it occurs, CS remains a highly fatal complication following an AMI,3 despite aggressive revascularization and other adjunctive therapies.3,4 Percutaneous ventricular assist devices (pVADs) have been shown to provide superior hemodynamic support compared to intraaortic balloon pump (IABP) counterpulsation.4,5 In light of the recently reported studies that have failed to show a hemodynamicorsurvivalbeneﬁtofIABPinthesetting ofpost‐AMICS,6–10physiciansmightadoptareﬂexive strategytousepVADsinthissettingmoreoften.While prospective randomized and adequately powered clinicaltrialsremainwarrantedtoevaluatethepotential beneﬁts of these new devices, real‐world observational data can be useful to provide clinical insights on their use in daily routine practice. In the present study, we sought to evaluate the current use of Impella 2.5 in patients with conﬁrmed CS complicating an AMI undergoing PCI. In particular, we were interested in evaluating the outcomes of patients who received hemodynamic support with Impella 2.5 (Abiomed, Inc., Danvers, MA, USA), prior to PCI versus those who received Impella 2.5 after PCI.
James Udelson, Harry P. Selker, Robin Ruthazer, Holger Thiele, Manesh R Patel, E. Magnus Ohman, Akiko Maehara, Paul L. Jenkins, Melissa Nichols, Ori Ben-Yehuda, Gregg W. Stone
Infarct size (IS) after MI is related to long-term outcomes. Whether a change in IS from an intervention is related to the intervention’s effect on outcomes is unknown. A therapy-induced change in IS is related in direction and/or magnitude to the outcome effect of that therapy. We combined patient-level data from 10 randomized clinical trials of therapies for STEMI. IS was assessed by sestamibi imaging or cardiac MR with analysis in core labs. Each patient within a trial was assigned a variable to represent a treatment’s mean effect on IS. Cox proportional hazards models estimated the association of treatment-related IS to one-year adjudicated clinical outcomes of hospitalization for HF and all-cause mortality. The 10 trials included 2,458 patients, 24% women. IS was measured at median 5 days post-MI. Mean trial IS in the control groups in the 10 trials ranged from 12% – 35% of the LV, and from 12% – 40% among treatment groups. There was a significant relation of treatment effect on IS to treatment effect on one-year HF hospitalization (HR 0.83, 95% CI 0.75 to 0.93, p<0.001). There was no significant relation between treatment effect on IS to treatment effect on one-year mortality (HR 1.04, 95% CI 0.94 to 1.15). The relation to HF hospitalization was stable in sensitivity analyses adjusting for time from MI to IS assessment, and for considering HF as the main outcome and death as a competing risk. This patient-level analysis of randomized placebo-controlled trials of multiple therapeutics for STEMI suggests that a treatment-induced effect on IS is related in direction and quantifiable magnitude to a treatment effect on HF hospitalizations. The data enable the consideration of incorporating infarct size assessment into novel trial analytic approaches as a surrogate endpoint to assess new therapeutics.
Michael Cohen, James M. Downey
Patients with AMI are treated with P2Y12 receptor antagonists to suppress platelet aggregation. Although P2Y12 antagonists are used for their anticoagulant effect, our studies reveal that they are also potent postconditioning-mimetics. The latter properties are influencing pre-clinical and clinical searches for adjunctive cardioprotective interventions in unexpected ways. In situ monkey, rabbit, and rat hearts were subjected to ischemia/reperfusion after which hearts were removed, areas at risk determined, and infarct size measured by triphenyltetrazolium chloride staining. Animals were given cangrelor, an intravenous P2Y12 antagonist, starting 10 min before reperfusion to simulate treatment of patients with AMI prior to angioplasty. Infarction was approximately half that seen in untreated animals. This cardioprotection was abrogated by inhibitors of signaling used by postconditioning including wortmannin, LY294002, PD98059, 5-hydroxydecanoate, 8-sulfophenyltheophylline, MRS1754, and 2-mercaptopropionylglycine suggesting that cangrelor protects by a similar mechanism. None restored platelet reactivity indicating that protection was independent of anti-coagulation. Our hypothesis was further strengthened by failure of ischemic pre- or postconditioning to potentiate cangrelor’s cardioprotection. Similar results were seen with clopidogrel and ticagrelor, other P2Y12 antagonists, indicating a class effect. We propose that much of the ability of P2Y12 inhibitors to improve outcomes in AMI can be attributed to direct infarct size reduction from conditioning rather than prevention of stent thrombosis. Because patients treated with P2Y12 antagonists prior to revascularization are already postconditioned, adding another conditioning intervention will be futile. This would explain why recent large trials of ischemic postconditioning or the postconditioning-mimetic cyclosporine in AMI patients were unsuccessful in spite of strong preclinical results. Additional protection in today’s patients will require an intervention not dependent on the conditioning mechanism. Any such intervention must first demonstrate additive protection in animals that have additionally been treated with a P2Y12 antagonist before clinical trials are considered.
Byung-Soo Ko, Iosif Taleb, Ryan Larsen, Anwar Tandar, Tae Soo Kang, Stephen McKellar, Josef Stehlik, Greg Stoddard, Antigone Koliopoulou, Edward M. Gilbert, Jose Nativi-Nicolau, James Fang, Craig Selzman, Frederick Welt, Stavros G. Drakos
The diversity in both the etiology and the clinical course of refractory cardiogenic shock makes the management of this critical condition challenging. Although a multidisciplinary team based approach has been recommended, it has not been widely adopted. We sought to investigate the feasibility and effectiveness of a multidisciplinary team approach in patients with RCS. A multidisciplinary “SHOCK TEAM”, comprised of a heart failure cardiologist, an interventional cardiologist, an intensivist, and a cardiothoracic surgeon, was established in April 2015 as a part of the Utah Cardiac Recovery-SHOCK program. The program prospectively investigates the management and outcomes of consecutive RCS patients who (i) require temporary percutaneous mechanical circulatory support (MCS) based on predefined criteria and clinical protocol, and (ii) are being managed by the SHOCK TEAM. Nineteen patients who have been enrolled since the launch of the program were compared with the immediately preceding 40 consecutive patients who presented with RCS requiring percutaneous MCS (control group). Baseline characteristics including age (56 vs. 55 in control), comorbidities, presenting hemodynamics, duration of shock before reaching the tertiary care center were comparable between the two groups. We found a marginally significant lower 30-day mortality in the SHOCK TEAM group in a Cox regression model (38.9% vs. 60% in control group; HR, 0.65, p=0.07). ICU stay and hospital stay also tended to be shorter in the SHOCK TEAM group (mean ± SD, 13 ± 13 vs. 27 ± 59 days in control, p=0.33 and 16 ± 15 vs. 31 ± 59 days in control, p=0.30). Furthermore, “Door-to-MCS implementation” time was compared between the groups to evaluate whether the team approach would lead to delays in management, and there was no significant difference. A multidisciplinary shock team approach seems to be feasible, practical, and may improve outcomes of patients with RCS.
Surenjav Chimed, Batmyagmar Khuyag
Intra‐aortic balloon pump (IABP) is the most widely used form of mechanical circulatory support in patients with cardiogenic shock. However, usefulness of IABP in this high risk patient population is conflicting. We examined whether the patient prognosis in Taiwan treated with IABP has improved when IABP was actively used for mechanical circulatory support. We used Taiwan’s National Health Insurance Research Database to retrospectively review 3145 (2358 men [75%]) cardiogenic shock patients who treated primary PCI due to acute myocardial infarction (AMI) between 2000 and 2012. Primary outcome was all cause mortality and secondary outcome was heart failure. A total of 1417 patients who received IABP therapy and 1728 patients who not received non-IABP were selected in this study. The mean age of IABP group and non-IABP group was 68.1±13.1 years and 67±13.3 years, respectively (p=0.02). Median follow-up time for death was 1.51 years in non-IABP group and 1.07 years in IABP group (p<0.0001). Median follow-up time for heart failure was 0.28 years in non-IABP group and 0.09 years in IABP group (p<0.0001). During follow-up period, the adjusted hazard ratio for overall mortality was 1.22 (CI 95% 1.10-1.35, p<0.0001) and for overall heart failure was 1.24 (CI 95% 1.08-1.41, p<0.001). Risk factors for all-cause mortality were previous heart failure, diabetes, chronic kidney disease and hypertension. In this nationwide, population-based, retrospective cohort study, we found that mortality rate and heart failure rate not declined in cardiogenic shock patients who underwent primary PCI plus IABP therapy. Therefore, new type of mechanical circulatory support such as Impella should be considered for high risk, cardiogenic shock patients with AMI.
Surenjav Chimed, Batmyagmar Khuyag, Amarjargal Baldandorj, Lkhagvasuren Zundui, Narantuya Davaakhuu
Acute pulmonary edema (APE) is common complication after ST elevation myocardial infarction (STEMI) and often associated with poor prognosis. It is usually caused by decreases of left ventricular contractility and subsequent increase of left ventricular afterload. In this study we aimed to determine association between left ventricular global longitudinal strain (GLS) parameter and APE caused by increased left ventricular afterload. We chose patients with STEMI and who were treated by primary PCI in this study. Two dimensional speckle tracking echocardiography was used to assess left ventricular GLS. Study endpoint was APE caused by increased left ventricular afterload. Univariable and multivariable logistic regression analysis was used to determine association between GLS and APE. A total of 524 patients were enrolled. Mean age was 60 ± 13 years old and majority of patients were male 444 (84.7%). During admission, APE was occurred in 15 (2.9%) patients. Univariable logistic regression analysis showed GLS is significantly associated with APE and every 1 unit change of GLS is associated with 1.34 times increased probability of having APE (OR 1.34, 95% CI 1.17-1.53, p<0.001). After adjustment of clinical, angiographic and conventional echocardiographic indices, left ventricular GLS was independently associated with APE (OR 1.25, 95% CI 1.06-1.46, p<0.01). Predictive capacity of left ventricular GLS was better than LVEF (c-statistic 0.824, 95% CI 0.719-0.929, p<0.001). Speckle tracking derived GLS is strong and independent predictor of APE caused by increased left ventricular afterload in patients with STEMI after primary PCI. Prognostic capacity of GLS is better than LVEF.
Dagmar M. Ouweneel, Krischan D. Sjauw, Esther M.A. Wiegerinck, Alexander Hirsh, Jan Baan Jr, Bas A.J.M. de Mol, Wim K. Lagrand, R. Nils Planken, José P.S. Henriques
Maintaining correct Impella position is a key factor for optimal functioning of the Impella device. The aortic valve is an important landmark for correct positioning. It would be of great value if the device position could be determined accurately by plain supine chest X-ray in the intensive care unit. The aim was to develop a ratio-based tool for determination of the aortic valve location on plain supine X-ray which can be used to monitor Impella position in the intensive care unit. Supine anterior-posterior chest X-ray of patients with an aortic valve prosthesis (n=473) were analyzed to determine the location of the aortic valve. We calculated several ratios with the potential to determine the position of the aortic valve. The Aortic Valve Location (AVL) ratio, defined as the distance between the carina and the aortic valve, divided by the thoracic width, was found to be the best performing ratio. The AVL ratio determines the location of the aortic valve caudal to the carina, at a distance of 0.25±0.05 times the thoracic width for male patients and 0.28±0.05 times the thoracic width for female patients. The AVL ratio was validated using computed tomography images of patients with angina pectoris without known valvular disease (n=95). There was a good correlation between the Impella position assessed with the AVL ratio and with echocardiography (n=53). The Aortic Valve Location Ratio enables accurate and reproducible localization of the aortic valve on supine chest X-ray. This tool is easily applicable and can be used for assessment of cardiac device position in patients on the ICU.