Percutaneous left ventricular assist devices during cardiogenic shock and high-risk percutaneous coronary interventions

Left ventricular assist devices were developed to support the function of a failing left ventricle. Owing to recent technological improvements, ventricular assist devices can be placed by percutaneous implantation techniques, which offer the advantage of fast implantation in the setting of acute left ventricular failure. This article reviews the growing evidence supporting the clinical use of left ventricular assist devices. Specifically, we discuss the use of left ventricular assist devices in patients with cardiogenic shock, in patients with acute ST-elevation myocardial infarction without shock, and during high-risk percutaneous coronary interventions.

Influence of left ventricular relaxation on the pressure half time of aortic regurgitation

BACKGROUND The severity of aortic regurgitation can be estimated using pressure half time (PHT) of the aortic regurgitation flow velocity, but the correlation between regurgitant fraction and PHT is weak. AIM To test the hypothesis that the association between PHT and regurgitant fraction is substantially influenced by left ventricular relaxation. METHODS In 63 patients with aortic regurgitation, subdivided into a group without (n = 22) and a group with (n = 41) left ventricular hypertrophy, regurgitant fraction was calculated using the difference between right and left ventricular cardiac outputs. Left ventricular relaxation was assessed using the early to late diastolic Doppler tissue velocity ratio of the mitral annulus (E/ADTI), the E/A ratio of mitral inflow (E/AM), and the E deceleration time (E-DT). Left ventricular hypertrophy was assessed using the M mode derived left ventricular mass index. RESULTS The overall correlation between regurgitant fraction and PHT was weak (r = 0.36, p < 0.005). In patients without left ventricular hypertrophy, there was a significant correlation between regurgitant fraction and PHT (r = 0.62, p < 0.005), but not in patients with left ventricular hypertrophy. In patients with a left ventricular relaxation abnormality (defined as E/ADTI< 1, E/AM< age corrected lower limit, E-DT >/= 220 ms), no associations between regurgitant fraction and PHT were found, whereas in patients without left ventricular relaxation abnormalities, the regurgitant fraction to PHT relations were significant (normal E/AM: r = 0.57, p = 0.02; E-DT< 220 ms: r = 0.50, p < 0.001; E/ADTI < 1: r = 0.57, p = 0.02). CONCLUSIONS Only normal left ventricular relaxation allows a significant decay of PHT with increasing aortic regurgitation severity. In abnormal relaxation, which is usually present in left ventricular hypertrophy, wide variation in prolonged backward left ventricular filling may cause dissociation between the regurgitant fraction and PHT. Thus the PHT method should only be used in the absence of left ventricular relaxation abnormalities.

Inhibition of Fas-associated death domain-containing protein (FADD) protects against myocardial ischemia/reperfusion injury in a heart failure mouse model

AIM As technological interventions treating acute myocardial infarction (MI) improve, post-ischemic heart failure increasingly threatens patient health. The aim of the current study was to test whether FADD could be a potential target of gene therapy in the treatment of heart failure. METHODS Cardiomyocyte-specific FADD knockout mice along with non-transgenic littermates (NLC) were subjected to 30 minutes myocardial ischemia followed by 7 days of reperfusion or 6 weeks of permanent myocardial ischemia via the ligation of left main descending coronary artery. Cardiac function were evaluated by echocardiography and left ventricular (LV) catheterization and cardiomyocyte death was measured by Evans blue-TTC staining, TUNEL staining, and caspase-3, -8, and -9 activities. In vitro, H9C2 cells transfected with ether scramble siRNA or FADD siRNA were stressed with chelerythrin for 30 min and cleaved caspase-3 was assessed. RESULTS FADD expression was significantly decreased in FADD knockout mice compared to NLC. Ischemia/reperfusion (I/R) upregulated FADD expression in NLC mice, but not in FADD knockout mice at the early time. FADD deletion significantly attenuated I/R-induced cardiac dysfunction, decreased myocardial necrosis, and inhibited cardiomyocyte apoptosis. Furthermore, in 6 weeks long term permanent ischemia model, FADD deletion significantly reduced the infarct size (from 41.20 ± 3.90% in NLC to 26.83 ± 4.17% in FADD deletion), attenuated myocardial remodeling, improved cardiac function and improved survival. In vitro, FADD knockdown significantly reduced chelerythrin-induced the level of cleaved caspase-3. CONCLUSION Taken together, our results suggest FADD plays a critical role in post-ischemic heart failure. Inhibition of FADD retards heart failure progression. Our data supports the further investigation of FADD as a potential target for genetic manipulation in the treatment of heart failure.

A Physiological Controller for Turbodynamic Ventricular Assist Devices Based on a Measurement of the Left Ventricular Volume

The current article presents a novel physiological control algorithm for ventricular assist devices (VADs), which is inspired by the preload recruitable stroke work. This controller adapts the hydraulic power output of the VAD to the end-diastolic volume of the left ventricle. We tested this controller on a hybrid mock circulation where the left ventricular volume (LVV) is known, i.e., the problem of measuring the LVV is not addressed in the current article. Experiments were conducted to compare the response of the controller with the physiological and with the pathological circulation, with and without VAD support. A sensitivity analysis was performed to analyze the influence of the controller parameters and the influence of the quality of the LVV signal on the performance of the control algorithm. The results show that the controller induces a response similar to the physiological circulation and effectively prevents over- and underpumping, i.e., ventricular suction and backflow from the aorta to the left ventricle, respectively. The same results are obtained in the case of a disturbed LVV signal. The results presented in the current article motivate the development of a robust, long-term stable sensor to measure the LVV.

Implantation of the continuous flow HeartWare(R) left ventricular assist device

Recent outstanding clinical advances with new mechanical circulatory systems have led to additional strategies in the treatment of end-stage heart failure. Heart transplantation can be postponed and for certain patients even replaced by smaller implantable left ventricular assist devices (LVADs). Mechanical support of the failing left ventricle enables appropriate haemodynamic stabilization and recovery of secondary organ failure, often seen in these severely ill patients. These new devices may be of great help to bridge patients until a suitable cardiac allograft is available but are also discussed as definitive treatment for patients who do not qualify for transplantation. Main indications for LVAD implantation are bridge to recovery, bridge to transplantation or destination therapy. An LVAD may be an important tool for patients with an expected prolonged period on the waiting list, for instance those with blood group O or B, with high or low body weight and those with potentially reversible secondary organ failure and pulmonary artery hypertension. However, LVAD implantation means an additional heart operation with inherent perioperative risks and complications during the waiting period. Finally, cardiac transplantation in patients with prior implantation of an LVAD represents a surgical challenge. The care of patients after the implantation of miniaturized LVADs, such as the HeartWare® system, seems to be easier than following pulsatile devices. The explantation of such devices at the time of transplantation is technically more comfortable than after HeartMate II implantation.

Percutaneous left-ventricular support with the Impella-2.5-assist device in acute cardiogenic shock: results of the Impella-EUROSHOCK-registry

BACKGROUND Acute cardiogenic shock after myocardial infarction is associated with high in-hospital mortality attributable to persisting low-cardiac output. The Impella-EUROSHOCK-registry evaluates the safety and efficacy of the Impella-2.5-percutaneous left-ventricular assist device in patients with cardiogenic shock after acute myocardial infarction. METHODS AND RESULTS This multicenter registry retrospectively included 120 patients (63.6±12.2 years; 81.7% male) with cardiogenic shock from acute myocardial infarction receiving temporary circulatory support with the Impella-2.5-percutaneous left-ventricular assist device. The primary end point evaluated mortality at 30 days. The secondary end point analyzed the change of plasma lactate after the institution of hemodynamic support, and the rate of early major adverse cardiac and cerebrovascular events as well as long-term survival. Thirty-day mortality was 64.2% in the study population. After Impella-2.5-percutaneous left-ventricular assist device implantation, lactate levels decreased from 5.8±5.0 mmol/L to 4.7±5.4 mmol/L (P=0.28) and 2.5±2.6 mmol/L (P=0.023) at 24 and 48 hours, respectively. Early major adverse cardiac and cerebrovascular events were reported in 18 (15%) patients. Major bleeding at the vascular access site, hemolysis, and pericardial tamponade occurred in 34 (28.6%), 9 (7.5%), and 2 (1.7%) patients, respectively. The parameters of age >65 and lactate level >3.8 mmol/L at admission were identified as predictors of 30-day mortality. After 317±526 days of follow-up, survival was 28.3%. CONCLUSIONS In patients with acute cardiogenic shock from acute myocardial infarction, Impella 2.5-treatment is feasible and results in a reduction of lactate levels, suggesting improved organ perfusion. However, 30-day mortality remains high in these patients. This likely reflects the last-resort character of Impella-2.5-application in selected patients with a poor hemodynamic profile and a greater imminent risk of death. Carefully conducted randomized controlled trials are necessary to evaluate the efficacy of Impella-2.5-support in this high-risk patient group.

Left ventricular torsion abnormalities in septic shock and corrective effect of volume loading: a pilot study

BACKGROUND Ventricular torsion is an important component of cardiac function. The effect of septic shock on left ventricular torsion is not known. Because torsion is influenced by changes in preload, we compared the effect of fluid loading on left ventricular torsion in septic shock with the response in matched healthy control subjects. METHODS We assessed left ventricular torsion parameters using transthoracic echocardiography in 11 patients during early septic shock and in 11 age- and sex-matched healthy volunteers before and after rapid volume loading with 250 mL of a Ringer's lactate solution. RESULTS Peak torsion and peak apical rotation were reduced in septic shock (10.2 ± 5.2° and 5.6 ± 5.4°) compared with healthy volunteers (16.3 ± 4.5° and 9.6 ± 1.5°; P = 0.009 and P = 0.006 respectively). Basal rotation was delayed and diastolic untwisting velocity reached its maximum later during diastole in septic shock patients than in healthy volunteers (104 ± 16% vs 111 ± 14% and 13 ± 5% vs 21 ± 10%; P = 0.03 and P = 0.034, respectively). Fluid challenge increased peak torsion in both groups (septic shock, 10.2 ± 5.3° vs 12.6 ± 3.9°; healthy volunteers, 16.3 ± 4.5° vs 18.1 ± 6°; P = 0.01). Fluid challenge increased left ventricular stroke volume in septic shock patients (P = 0.003). CONCLUSIONS Compared with healthy volunteers, left ventricular torsion is impaired in septic shock patients. Fluid loading attenuates torsion abnormalities in parallel with increasing stroke volume. Reduced torsional motion might constitute a relevant component of septic cardiomyopathy, a notion that merits further testing in larger populations.

Progressive regression of left ventricular hypertrophy two years after bariatric surgery.

BACKGROUND: Obesity is a systemic disorder associated with an increase in left ventricular mass and premature death and disability from cardiovascular disease. Although bariatric surgery reverses many of the hormonal and hemodynamic derangements, the long-term collective effects on body composition and left ventricular mass have not been considered before. We hypothesized that the decrease in fat mass and lean mass after weight loss surgery is associated with a decrease in left ventricular mass. METHODS: Fifteen severely obese women (mean body mass index [BMI]: 46.7+/-1.7 kg/m(2)) with medically controlled hypertension underwent bariatric surgery. Left ventricular mass and plasma markers of systemic metabolism, together with body mass index (BMI), waist and hip circumferences, body composition (fat mass and lean mass), and resting energy expenditure were measured at 0, 3, 9, 12, and 24 months. RESULTS: Left ventricular mass continued to decrease linearly over the entire period of observation, while rates of weight loss, loss of lean mass, loss of fat mass, and resting energy expenditure all plateaued at 9 [corrected] months (P <.001 for all). Parameters of systemic metabolism normalized by 9 months, and showed no further change at 24 months after surgery. CONCLUSIONS: Even though parameters of obesity, including BMI and body composition, plateau, the benefits of bariatric surgery on systemic metabolism and left ventricular mass are sustained. We propose that the progressive decrease of left ventricular mass after weight loss surgery is regulated by neurohumoral factors, and may contribute to improved long-term survival.

A genetically engineered, adherent smooth muscle cell lining for left ventricular assist devices

Due to the clinical success of left ventricular assist devices (LVADs) used for short term "bridge to transplant" and the limited availability of donor organs, heart assist devices are being considered for long term implantation as an alternative to heart transplantation. In an effort to improve biocompatibility, a nonthrombogenic cellular lining was developed from genetically engineered smooth muscle cells (GE-SMC) for the Thermocardiosystems Heartmate$\sp{\rm TM}$ LVAD. SMCs have been transduced with the genes for endothelial nitric oxide synthase (NOS III) and GTP cyclohydrolase (GTPCH) with subsequent stable expression of the NOS III protein via an Epstein Barr based DNA expression vector. Transduced SMCs produce nitric oxide at concentrations that reduce platelet deposition and smooth muscle cell proliferation when tested in vitro. In addition, the adhesive capabilities of GE-SMC linings were also examined, and optimized in physical environments mimicking typical in vivo LVAD operation. Preliminary investigations examining cell adhesion during constant shear stress exposure demonstrated an acute phase of cell loss corresponding to cytoskeletal F-actin rearrangement. Subsequently, an in vitro circulatory loop was designed to expose cell lined LVADs to in vivo operating conditions. Cumulative cell loss from cell lined LVADs was less than 10% after 24 hours of flow. Using a protocol for "preconditioning" the cell lining within the mock circulatory loop, the first implantation of an LVAD containing a genetically engineered SMC lining was successfully implemented in a bovine model. Results from this 24 hour study indicate that the flow-conditioned cellular lining remained intact with no evidence of thromboembolization and only minimal changes in coagulation studies. ^

Left ventricular growth from age 8 to 18 and its anthropometric determinants: Longitudinal results from Project Heartbeat!

Left ventricular mass (LVM) is a strong predictor of cardiovascular disease (CVD) in adults. However, normal growth of LVM in healthy children is not well understood, and previous results on independent effects of body size and body fatness on LVM have been inconsistent. The purpose of this study was (1) to establish the normal growth curve of LVM from age 8 to age 18, and evaluate the determinants of change in LVM with age, and (2) to assess the independent effects of body size and body fatness on LVM.^ In Project HeartBeat!, 678 healthy children aged 8, 11 and 14 years at baseline were enrolled and examined at 4-monthly intervals for up to 4 years. A synthetic cohort with continuous observations from age 8 to 18 years was constructed. A total of 4608 LVM measurements was made from M-mode echocardiography. The multilevel linear model was used for analysis.^ Sex-specific trajectories of normal growth of LVM from age 8 to 18 was displayed. On average, LVM was 15 g higher in males than females. Average LVM increased linearly in males from 78 g at age 8 to 145 g at age 18. For females, the trajectory was curvilinear, nearly constant after age 14. No significant racial differences were found. After adjustment for the effects of body size and body fatness, average LVM decreased slightly from age 8 to 18, and sex differences in changes of LVM remained constant.^ The impact of body size on LVM was examined by adding to a basic LVM-sex-age model one of 9 body size indicators. The impact of body fatness was tested by further introducing into each of the 9 LVM models (with one or another of the body size indicators) one of 4 body fatness indicators, yielding 36 models with different body size and body fatness combinations. The results indicated that effects of body size on LVM can be distinguished between fat-free body mass and fat body mass, both being independent, positive predictors. The former is the stronger determinant. When a non-fat-free body size indicator is used as predictor, the estimated residual effect of body fatness on LVM becomes negative. ^