The Utility of a Wireless Implantable Hemodynamic Monitoring System in Patients Requiring Mechanical Circulatory Support.

Proper timing of left ventricular assist device (LVAD) implantation in advanced heart failure patients is not well established and is an area of intense interest. In addition, optimizing LVAD performance after implantation remains difficult and represents a significant clinical need. Implantable hemodynamic monitoring systems may provide physicians with the physiologic information necessary to improve the timing of LVAD implantation as well as LVAD performance when compared with current methods. The CardioMEMS Heart sensor Allows for Monitoirng of Pressures to Improve Outcomes in NYHA Class III heart failure patients (CHAMPION) Trial enrolled 550 previously hospitalized patients with New York Heart Association (NYHA) class III heart failure. All patients were implanted with a pulmonary artery (PA) pressure monitoring system and randomized to a treatment and control groups. In the treatment group, physicians used the hemodynamic information to make heart failure management decisions. This information was not available to physicians for the control group. During an average of 18 month randomized follow-up, 27 patients required LVAD implantation. At the time of PA pressure sensor implantation, patients ultimately requiring advanced therapy had higher PA pressures, lower systemic pressure, and similar cardiac output measurements. Treatment and control patients in the LVAD subgroup had similar clinical profiles at the time of enrollment. There was a trend toward a shorter length of time to LVAD implantation in the treatment group when hemodynamic information was available. After LVAD implantation, most treatment group patients continued to provide physicians with physiologic information from the hemodynamic monitoring system. As expected PA pressures declined significantly post LVAD implant in all patients, but the magnitude of decline was higher in patients with PA pressure monitoring. Implantable hemodynamic monitoring appeared to improve the timing of LVAD implantation as well as optimize LVAD performance when compared with current methods. Further studies are necessary to evaluate these findings in a prospective manner.

Percutaneous Venoarterial Extracorporeal Membrane Oxygenation for Refractory Cardiogenic Shock Is Associated with Improved Short- and Long-Term Survival.

Mortality due to refractory cardiogenic shock (RCS) exceeds 50%. Venoarterial extracorporeal membrane oxygenation (VA-ECMO) has become an accepted therapy for RCS. The aim of our study was to evaluate outcomes of patients with RCS treated with percutaneous VA-ECMO (pVA-ECMO). Retrospective review of patients supported with VA-ECMO at our institution in 2012-2013. Clinical characteristics, bleeding, vascular complications, and outcomes including survival were assessed. A total of 37 patients were supported with VA-ECMO for RCS. The majority of VA-ECMO (76%) was placed in the catheterization laboratory. Nearly half (49%) of the patients presented with acute myocardial infarction. Seven patients (19%) underwent insertion of pVA-ECMO in the setting of cardiopulmonary resuscitation with mechanical chest compression device. Median duration of support was 5 days. Index hospitalization, 30-day, and 1-year survival were 65%, 65%, and 57%, respectively. Survival rate for discharged patients was 87.5% with a median follow-up of 450 days. Refractory cardiogenic shock supported with pVA-ECMO is associated with an improved survival in patients with a traditionally poor prognosis.

Relationship of right- and left-sided filling pressures in patients with advanced heart failure: a 14-year multi-institutional analysis.

BACKGROUND: Jugular venous pressure (JVP) is assessed to estimate volume status in patients with heart failure because right atrial pressure (RAP) reflects pulmonary capillary wedge pressure (PCWP). In a large cohort of heart failure patients spanning 14 years, we sought to further characterize the relationship between RAP and PCWP, including identifying temporal trends, to optimize estimates of PCWP by JVP. We also sought to determine whether the RAP to PCWP relationship impacts post-transplant mortality. METHODS: Hemodynamic data were obtained from 4,079 patients before cardiac transplantation. Elevated RAP was defined as ≥10 mm Hg and elevated PCWP ≥22 mm Hg. Hemodynamics were "concordant" when both RAP and PCWP were elevated or when both were not elevated. The frequency of concordant hemodynamics was assessed over 3 eras (1993 to 1997, 1998 to 2002, 2003 to 2007). Baseline characteristics were compared among quartiles of the ratio (RAP+1)/PCWP. The association of (RAP+1)/PCWP with 2-year mortality after cardiac transplantation was assessed using multivariate models. RESULTS: The frequency of concordant hemodynamics over time was stable (74%, 72%, 73%; p = 0.4). Increasing (RAP+1)/PCWP was associated with the following variables: female gender; cardiomyopathy etiology besides ischemic or non-ischemic; prior sternotomies; and lower creatinine clearance (p < 0.01 for all). Elevated (RAP+1)/PCWP was associated with post-transplant mortality (relative risk 1.2, 95% confidence interval 1.02 to 1.37, p = 0.02). CONCLUSIONS: [corrected] RAP and PCWP remain concordant in most heart failure patients, supporting the ongoing use of JVP to estimate PCWP. Easily identifiable patient characteristics were associated with an increased RAP/PCWP ratio, and their presence should alert clinicians that PCWP may be overestimated by JVP assessment. A higher RAP/PCWP ratio was an adverse risk factor for post-cardiac transplant survival.

The impact of prolonged rotary ventricular assist device support upon ventricular geometry and flow kinetics.

BACKGROUND: The aim of this study was to determine the impact of prolonged left ventricular assist device (VAD) support on cardiac ventricular geometry and VAD flow kinetics. METHODS: Nineteen patients with end-stage heart failure underwent the implantation of HeartMate II rotary flow VADs. Left and right ventricular geometry and VAD flow kinetics were assessed by transthoracic echocardiography early (7 ± 1 days) and late (113 ± 21 days) after VAD implantation. RESULTS: Left ventricular end-diastolic internal dimension decreased by 21% and 35%, respectively, early and late after VAD implantation (n = 19; P < .001 vs before VAD implantation). Right ventricular end-diastolic internal dimension did not decrease at either time. Hemodynamic trends were similar. VAD inflow obstruction by myocardium was observed in eight patients, seven of whom demonstrated significantly increased variation of VAD inflow during the cardiac cycle ("pulsatility") detected by Doppler studies. Medical or surgical intervention returned VAD flow patterns toward baseline in seven of eight patients with VAD obstructions. CONCLUSIONS: Prolonged rotary VAD support unloads the left ventricle, with modest effects on the right ventricle. These changes are often associated with alterations of VAD flow kinetics, requiring therapeutic intervention. These findings indicate the usefulness of echocardiographic surveillance in patients undergoing prolonged VAD support.

Door-to-VAD time: an expedient management strategy for cardiogenic shock.

PURPOSE OF REVIEW: Emerging devices are now providing full hemodynamic support and may improve survival in patients who present with cardiogenic shock. This manuscript will present the framework strategy for utilizing current advancements in temporary device therapy for acutely decompensated patients with cardiogenic shock, as a stabilizing bridge-to-decision (BTD) modality. We identify criteria for the clinical presentation of cardiogenic shock and a list of factors that suggest inferior outcomes. RECENT FINDINGS: Cardiogenic shock continues to be associated with significant morbidity and mortality. The observed poor outcomes are usually impacted by delayed recognition and limited pharmacologic options. Initial therapeutic responses are often temporarily successful, but fail to adequately resuscitate many patients who ultimately die of multiorgan system or septic deaths. SUMMARY: We will describe essential clinical components to assist in identifying such patients for short-term circulatory support as a BTD for advanced durable ventricular assist devices. Improved outcomes of patients with cardiogenic shock may be achieved by both early clinical recognition and early strategic implementation of sustainable temporary circulatory support.

Continuous aortic flow augmentation: a pilot study of hemodynamic and renal responses to a novel percutaneous intervention in decompensated heart failure.

BACKGROUND: Diminished aortic flow may induce adverse downstream vascular and renal signals. Investigations in a heart failure animal model have shown that continuous aortic flow augmentation (CAFA) achieves hemodynamic improvement and ventricular unloading, which suggests a novel therapeutic approach to patients with heart failure exacerbation that is inadequately responsive to medical therapy. METHODS AND RESULTS: We studied 24 patients (12 in Europe and 12 in the United States) with heart failure exacerbation and persistent hemodynamic derangement despite intravenous diuretic and inotropic and/or vasodilator treatment. CAFA (mean+/-SD 1.34+/-0.12 L/min) was achieved through percutaneous (n=19) or surgical (n=5) insertion of the Cancion system, which consists of inflow and outflow cannulas and a magnetically levitated and driven centrifugal pump. Hemodynamic improvement was observed within 1 hour. Systemic vascular resistance decreased from 1413+/-453 to 1136+/-381 dyne.s.cm(-5) at 72 hours (P=0.0008). Pulmonary capillary wedge pressure decreased from 28.5+/-4.9 to 19.8+/-7.0 mm Hg (P<0.0001), and cardiac index (excluding augmented aortic flow) increased from 1.97+/-0.44 to 2.27+/-0.43 L.min(-1).m(-2) (P=0.0013). Serum creatinine trended downward during treatment (overall P=0.095). There were 8 complications during treatment, 7 of which were self-limited. Hemodynamics remained improved 24 hours after CAFA discontinuation. CONCLUSIONS: In patients with heart failure and persistent hemodynamic derangement despite intravenous inotropic and/or vasodilator therapy, CAFA improved hemodynamics, with a reduction in serum creatinine. CAFA represents a promising, novel mode of treatment for patients who are inadequately responsive to medical therapy. The clinical impact of the observed hemodynamic improvement is currently being explored in a prospective, randomized, controlled trial.

Differential activation of stress-response signaling in load-induced cardiac hypertrophy and failure.

Hypertrophic growth of the myocardium occurs in most forms of heart failure and may contribute to the pathogenesis of the failure state. Little is known about the regulatory mechanisms governing the often-coexisting phenotypes of hypertrophy, systolic failure, and diastolic stiffness that characterize clinical disease. We hypothesized that intracellular signaling pathways are differentially activated by graded degrees of hemodynamic stress. To test this, we developed models of graded pressure stress in mice and used them to directly compare compensated hypertrophy and pressure-overload heart failure. Surgical interventions were designed to be similar, on either side of a threshold separating compensated from decompensated responses. Our findings revealed two dramatically different hypertrophic phenotypes with only modest differences in the activation of relevant intracellular signaling pathways. Furthermore, we uncovered a functional requirement of calcineurin signaling in each model such that calcineurin suppression blunted hypertrophic growth. Remarkably, in each case, suppression of calcineurin signaling was not associated with clinical deterioration or increased mortality. Profiles of stress-response signaling and Ca2+ handling differ between the steady-state, maintenance phases of load-induced cardiac hypertrophy and failure. This information may be useful in identifying novel targets of therapy in chronic disease.

Targeted inhibition of calcineurin in pressure-overload cardiac hypertrophy. Preservation of systolic function.

Calcineurin is a Ca(2+)/calmodulin-activated protein phosphatase that transduces hypertrophic stimuli to regulate transcriptional control of myocyte transformation. It is not known whether overexpression of MCIP1, a recently described endogenous inhibitor of calcineurin, impacts the hypertrophic response to pathophysiologically relevant pressure overload. Further, the functional consequences of calcineurin inhibition by MCIP1 under conditions of hemodynamic stress are unknown. Transgenic mice expressing a human cDNA encoding hMCIP1 in the myocardium were subjected to thoracic aortic banding. Transgenic mice and wild type littermates tolerated pressure overload equally well. Wild type mice developed left ventricular hypertrophy, but the hypertrophic response in transgenics was significantly blunted. An isoform of MCIP1 transcript was up-regulated by pressure stress, whereas MCIP2 transcript was not. Expression patterns of fetal genes were differentially regulated in banded MCIP1 hearts compared with wild type. Echocardiography performed at 3 weeks and 3 months revealed preservation of both left ventricular size and systolic function in banded MCIP1 mice despite the attenuated hypertrophic response. These data demonstrate attenuation of hypertrophic transformation when calcineurin is inhibited by MCIP1. Further, these data suggest that activation of hypertrophic marker genes may not be directly dependent on calcineurin activity. Finally, they demonstrate that ventricular performance is preserved despite attenuation of compensatory hypertrophy.