Incidence and predictors of cardiogenic shock following surgical or transcatheter tricuspid valve intervention.

OBJECTIVE: The objective of this study was to evaluate the incidence of and risk factors associated with cardiogenic shock (CS) following surgery versus transcatheter tricuspid valve intervention (TTVI) for tricuspid regurgitation (TR). BACKGROUND: Surgical therapy for TR is associated with high rates of CS. Postprocedural shock has not been studied following TTVI. METHODS: We performed a single-center retrospective analysis of isolated tricuspid valve (TV) surgery or TTVI for TR. The primary outcome was postprocedural class D or E CS according to Society for Cardiovascular Angiography and Interventions (SCAI) CS classification scheme, and secondary outcome was in-hospital mortality. Multivariable logistic regression modeling was performed for primary and secondary outcomes. Support vector machine analysis was performed for sensitivity analysis. RESULTS: From 2008 to 2020, a total of 122 patients underwent isolated TV surgery (n = 58, 14 TV repair, and 44 TV replacement) or TTVI (n = 64, 36 TV repair, and 28 TV replacement). Surgical patients were significantly younger than TTVI patients (67.5 vs. 80 years, p < 0.0001). Multivariable modeling revealed an association between the primary outcome and surgery (odds ratio [OR]: 8.75, 95% confidence interval [CI]: 2.83, 27.03, p = 0.0002), as well as baseline central venous pressure (CVP, OR: 1.12, 95% CI: 1.02, 1.22, p = 0.016). Additionally, class DE CS was independently associated with in-hospital mortality (OR: 5.21, 1.35, 20.09, p = 0.016). CVP and surgery were found to have highest importance indices in support vector machine analysis. CONCLUSION: In patients undergoing TV intervention for TR, surgery versus TTVI and elevated CVP are associated with advanced postprocedural CS. Patients developing advanced CS are at increased risk of in-hospital mortality.

Position Paper on Global Extracorporeal Membrane Oxygenation Education and Educational Agenda for the Future: A Statement From the Extracorporeal Life Support Organization ECMOed Taskforce.

OBJECTIVES: The purpose of this position paper is two-fold: first, to describe the state of extracorporeal membrane oxygenation education worldwide, noting current limitations and challenges; and second, to put forth an educational agenda regarding opportunities for an international collaborative approach toward standardization. DESIGN: Relevant medical literature was reviewed through literature search, and materials from national organizations were accessed through the Internet. Taskforce members generated a consensus statement using an iterative consensus process through teleconferences and electronic communication. SETTING: In 2018, the Extracorporeal Life Support Organization convened the ECMOed Taskforce at two structured, face-to-face meetings of 40 healthcare practitioners and educators with expertise in caring for the extracorporeal membrane oxygenation patient and in extracorporeal membrane oxygenation education. PATIENTS: None. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The ECMOed Taskforce identified seven educational domains that would benefit from international collaborative efforts. Of primary importance, the Taskforce outlined actionable items regarding 1) the creation of a standardized extracorporeal membrane oxygenation curriculum; 2) defining criteria for an extracorporeal membrane oxygenation course as a vehicle for delivering the curriculum; 3) outlining a mechanism for evaluating the quality of educational offerings; 4) utilizing validated assessment tools in the development of extracorporeal membrane oxygenation practitioner certification; and 5) promoting high-quality educational research to guide ongoing educational and competency assessment development. CONCLUSIONS: Significant variability and limitations in global extracorporeal membrane oxygenation education exist. In this position paper, we outline a road map for standardizing international extracorporeal membrane oxygenation education and practitioner certification. Ongoing high-quality educational research is needed to evaluate the impact of these initiatives.

Extracorporeal Membrane Oxygenation for End-Stage Interstitial Lung Disease With Secondary Pulmonary Hypertension at Rest and Exercise: Insights From Simulation Modeling.

Interstitial lung disease (ILD) represents a collection of lung disorders with a lethal trajectory with few therapeutic options with the exception of lung transplantation. Various extracorporeal membrane oxygenation (ECMO) configurations have been used for bridge to transplant (BTT), yet no optimal configuration has been clearly demonstrated. Using a cardiopulmonary simulation, we assessed different ECMO configurations for patients with end-stage ILD to assess the physiologic deficits and help guide the development of new long-term pulmonary support devices. A cardiopulmonary ECMO simulation was created, and changes in hemodynamics and blood gases were compared for different inflow and outflow anatomic locations and for different sweep gas and blood pump flow rates. The system simulated the physiologic response of patients with severe ILD at rest and during exercise with central ECMO, peripheral ECMO, and with no ECMO. The output parameters were total cardiac output (CO), mixed venous oxygen (O2) saturation, arterial pH, and O2 delivery (DO2)/O2 utilization (VO2) at different levels of exercise. The model described the physiologic state of progressive ILD and showed the relative effects of using various ECMO configurations to support them. It elucidated the optimal device configurations and required physiologic pump performance and provided insight into the physiologic demands of exercise in ILD patients. The simulation program was able to model the pathophysiologic state of progressive ILD with PH and demonstrate how mechanical support devices can be implemented to improve cardiopulmonary function at rest and during exercise. The information generated from simulation can be used to optimize ECMO configuration selection for BTT patients and provide design guidance for new devices to better meet the physiologic demands of exercise associated with normal activities of daily living.

The Starling Relationship and Veno-Arterial ECMO: Ventricular Distension Explained.

The use of veno-arterial (VA) extracorporeal membrane oxygenation (ECMO) to support patients with acute heart failure has been associated with ventricular distension and pulmonary edema, the mechanism of which is not fully understood. This study examined the impact of VA ECMO on left ventricular (LV) Starling curves to elaborate a framework for anticipating and treating LV distension. A previously developed and validated model of the cardiovascular system was used to generate pressure-volume (PV) loops and Starling curves while holding mean arterial pressure (mABP) constant at a range of values either by adjusting systemic resistance or by adding VA ECMO support. It was found that under all conditions of similar mAPB, the Starling curve was unchanged; therefore, the degree of LV distension is obligated by the mAPB (irrespective of whether controlled pharmacologically with or without ECMO support and independent of heart rate), LV contractility, and target stroke volume. The Starling relationship provides a conceptual framework for understanding the risk and treatment of LV distension during VA ECMO support.

Physiologic determinants of mitral inflow pattern using a computer simulation: insights into Doppler echocardiography in diverse phenotypes.

BACKGROUND: Although echo Doppler recordings of mitral inflow patterns are often employed clinically to identify "diastolic dysfunction," abnormal flow profiles may be seen in a diverse set of disorders in which the specific physiologic determinants are not well defined. METHODS: We used a validated cardiovascular simulation model to assess the effects of four hemodynamic parameters on Doppler measures of LV filling: (1) total blood volume, (2) diastolic stiffness (LV Beta), (3) systemic vascular resistance (SVR), and (4) pulmonary vascular resistance (PVR). In each simulation, we calculated instantaneous flow through the mitral valve as a function of time. RESULTS: Increases in blood volume led to an increase in the E:A ratio and a decrease in deceleration time (DT), such that for every 100 mL of volume, DT decreased by approximately 3 ms. Increases in LV Beta increased the E:A ratio and decreased DT such that for every 0.005 mmHg/mL increase in LV Beta, DT decreased by approximately 8 ms. While changes in SVR did not significantly alter the Doppler pattern, increases in PVR effected a prolongation of DT and an impaired relaxation E:A pattern. Increasing blood volume and LV Beta simultaneously was additive, while increasing PVR attenuated the effect of increasing volume on the E:A ratio. CONCLUSIONS: Computer simulations demonstrate that both blood volume and LV stiffness significantly impact the mitral inflow profile indicating that both filling pressure and intrinsic properties of the ventricle are contributors. These data confirm that there are multiple determinants of the Doppler mitral inflow pattern and suggest a new approach toward understanding complex physiologic interactions.

Severe pulmonary hypertension due to chronic echinococcal pulmonary emboli treated with targeted pulmonary vascular therapy and hepatic resection.

Hydatid disease (human echinococcosis) is a zoonotic infection caused by larval forms (metacestodes) of the genus Echinococcus. Although pulmonary hypertension (PH) due to hydatid disease has been described, it is quite rare. We report a patient with chronic echinococcal embolic PH in whom treatment with novel PH therapies permitted successful resection of the hepatic cyst with a good outcome.

A computational method of prediction of the end-diastolic pressure-volume relationship by single beat.

The end-diastolic pressure-volume relation (EDPVR) is an important descriptor of passive cardiac pump properties. However, clinical utility has been limited by the need for measurement of pressures and volumes over relatively large ranges. In this protocol, we describe an algorithm to estimate the entire EDPVR in humans from a single measured pressure-volume (P-V) point. This algorithm was developed from observations made from accurately measured EDPVRs of human hearts, which indicated that when normalized by appropriate left ventricular volume scaling (to arrive at volume-normalized EDPVRs, EDPVR(n)) EDPVR(n)s were nearly identical in all patients. In this protocol, we demonstrate how to use EDPVR(n)s to predict a second P-V point on the EDPVR, in which case the entire EDPVR can then be predicted. With recent advances for accurate noninvasive measurement of end-diastolic pressure and volumes, this protocol permits the assessment of passive properties in a broader range of research and clinical settings.

Single-beat estimation of end-diastolic pressure-volume relationship: a novel method with potential for noninvasive application.

Whereas end-systolic and end-diastolic pressure-volume relations (ESPVR, EDPVR) characterize left ventricular (LV) pump properties, clinical utility of these relations has been hampered by the need for invasive measurements over a range of pressure and volumes. We propose a single-beat approach to estimate the whole EDPVR from one measured volume-pressure (Vm and Pm) point. Ex vivo EDPVRs were measured from 80 human hearts of different etiologies (normal, congestive heart failure, left ventricular assist device support). Independent of etiology, when EDPVRs were normalized (EDPVRn) by appropriate scaling of LV volumes, EDPVRns were nearly identical and were optimally described by the relation EDP = An.EDV (Bn), with An = 28.2 mmHg and Bn = 2.79. V0 (the volume at the pressure of approximately 0 mmHg) was predicted by using the relation V0 = Vm.(0.6 - 0.006.Pm) and V30 by V30 = V0 + (Vm,n - V0)/(Pm/An) (1/Bn). The entire EDPVR of an individual heart was then predicted by forcing the curve through Vm, Pm, and the predicted V0 and V30. This technique was applied prospectively to the ex vivo human EDPVRs not used in determining optimal An and Bn values and to 36 in vivo human, 12 acute and 14 chronic canine, and 80 in vivo and ex vivo rat studies. The root-mean-square error (RMSE) in pressure between measured and predicted EDPVRs over the range of 0-40 mmHg was < 3 mmHg of measured EDPVR in all settings, indicating a good predictive value of this approach. Volume-normalized EDPVRs have a common shape, despite different etiology and species. This allows the entire curve to be predicted by a new method with a potential for noninvasive application. The results are most accurate when applied to groups of hearts rather than to individual hearts.

Mechanical unloading during left ventricular assist device support increases left ventricular collagen cross-linking and myocardial stiffness.

BACKGROUND: Left ventricular assist devices (LVADs) induce reverse remodeling of the failing heart except for the extracellular matrix, which exhibits additional pathophysiological changes, although their mechanisms and functional consequences are unknown. METHODS AND RESULTS: Hearts were obtained at transplant from patients with idiopathic dilated cardiomyopathy (DCM) not requiring LVAD support (n=30), patients requiring LVAD support (n=16; LVAD duration, 145+/-33 days), and 5 nonfailing hearts. Left (LV) and right ventricular (RV) ex vivo pressure-volume relationships were measured, and chamber and myocardial stiffness constants were determined. Myocardial tissue content of total and cross-linked collagen, collagen types I and III, MMP-1, MMP-9, TIMP-1, and angiotensin (Ang) I and II were measured. LV size, mass, and myocyte diameter decreased after LVAD compared with DCM without LVAD (P<0.05). Total and cross-linked collagen and ratio of type I to III collagen increased in DCM compared with nonfailing hearts and increased further after LVAD (P<0.05 versus DCM and nonfailing). Concomitantly, chamber and myocardial stiffness increased with LVAD. The ratio of MMP-1 to TIMP-1 increased in DCM and almost normalized after LVAD, favoring decreased collagen degradation. Tissue Ang I and II also increased during LVAD. There was no significant change in the RV of LVAD-supported heart compared with DCM. CONCLUSIONS: LVAD support increases LV collagen cross-linking and the ratio of collagen type I to III, which is associated with increased myocardial stiffness. Decreased tissue MMP-1-to-TIMP-1 ratio (decreased degradation) and increased Ang levels (stimulants of synthesis) are likely mechanisms for these changes. Lack of significant effects on the RV suggest that hemodynamic unloading of the LV (not provided to the RV) might be the primary factor that regulates these extracellular matrix changes.

Mechanisms of heart failure with well preserved ejection fraction in dogs following limited coronary microembolization.

OBJECTIVE: It has been suggested that in some settings, heart failure (HF) may occur with normal ejection fraction (EF) as a consequence of undetected systolic dysfunction. However, others have argued that this can only occur in the presence of diastolic dysfunction. We therefore sought to determine the contribution of diastolic dysfunction in an animal model of HF with normal EF. METHODS AND RESULTS: Limited myocardial injury was induced in 21 dogs chronically instrumented to measure hemodynamics and LV properties by daily coronary microembolization ( approximately 115 microm beads) until LV end diastolic pressure (LVEDP) was > or =16 mm Hg. Nine dogs developed HF within 16+/-6 days (LVEDP 12+/-2 vs. 21+/-2 mm Hg, p<0.001) with no significant change in dP/dt(max) (2999+/-97 vs. 2846+/-189 mm Hg/s), mean arterial pressure (103+/-4 vs. 100+/-4 mm Hg), EF (57+/-5% vs. 53+/-4%) or E(es) (end-systolic elastance, 3.1+/-0.9 vs. 2.9+/-0.8 mm Hg/ml) but with an approximately 10 ml increase in V(o) (14+/-12 vs. 25+/-16 ml; p<0.01). The EDPVR and time constant of relaxation (tau, 25+/-3 vs. 28+/-3 ms) did not change significantly. These animals were hemodynamically stable out to 3 1/2 months. Neurohormonal activation occurred (elevations of NE, AngII, BNP) and there was intravascular volume expansion by approximately 16% (p<0.05). CONCLUSIONS: A small amount of myocardial injury can lead to neurohormonal activation with intravascular volume expansion and elevation of LVEDP in the absence of reductions in dP/dt(max) or EF and without diastolic dysfunction. Thus, HF with preserved EF does not a priori equate with diastolic heart failure.

Transesophageal echocardiography guided placement of a coronary sinus pacing lead.

Cardiac resynchronization therapy for the treatment of medically refractory heart failure requires coronary sinus lead placement for left ventricular pacing. Coronary sinus lead placement is technically difficult with success rates reported between 53% to 98% and implantation times ranging from 90 minutes to 5 hours. We report the use of intraoperative transesophageal echocardiography to guide coronary sinus lead placement when conventional fluoroscopy failed. Transesophageal echocardiography may improve the success rate with coronary sinus lead placement and decrease the operative time required. This should be used with caution, however, as sedation, possible intubation, and esophageal manipulation have potentially morbid consequences in patients with advanced congestive heart failure.

Cardiac contractility modulation by electric currents applied during the refractory period.

Inotropic effects of electric currents applied during the refractory period have been reported in cardiac muscle in vitro using voltage-clamp techniques. We investigated how electric currents modulate cardiac contractility in normal canine hearts in vivo. Six dogs were instrumented to measure regional segment length, ventricular volume (sonomicrometry), and ventricular pressure. Cardiac contractility modulating (CCM) electric currents (biphasic square pulses, amplitude +/-20 mA, total duration 30 ms) were delivered during the refractory period between pairs of electrodes placed on anterior and posterior walls. CCM significantly increased index of global contractility (E(es)) from 5.9 +/- 2.9 to 8.3 +/- 4.6 mmHg/ml with anterior CCM, from 5.3 +/- 1.8 to 8.9 +/- 4.0 mmHg/ml with posterior CCM, and from 6.1 +/- 2.6 to 11.0 +/- 7.0 mmHg/ml with combined CCM (P < 0.01, no significant change in volume axis intercept). End-systolic pressure-segment length relations showed contractility enhancement near CCM delivery sites, but not remotely. Relaxation was not influenced. CCM increased mean aortic pressure, but did not change peripheral resistance. Locally applied electrical currents enhanced global cardiac contractility via regional changes in myocardial contractility without impairing relaxation in situ.