Time course of reverse remodeling of the left ventricle during support with a left ventricular assist device

BACKGROUND: Support with a left ventricular assist device leads to normalization of left ventricular chamber geometry, regression of myocyte hypertrophy, alterations in left ventricular collagen content, and normalized expression of genes involved with excitation-contraction coupling in patients with heart failure. The objective of this study was to investigate the time course of these processes. METHODS: Passive left ventricular pressure-volume relationships were obtained from explanted hearts of 19 patients with heart failure undergoing transplantation without left ventricular assist device support, 25 patients with heart failure supported before transplantation (duration of support ranging between 8 and 155 days), and 5 normal human hearts not suitable for transplantation. Left ventricular size was indexed by the volume at which left ventricular pressure reached 30 mm Hg. Left ventricular tissue samples were probed for sarcoplasmic endoreticular calcium adenosine triphosphatase 2a expression and processed for analysis of myocyte diameter and relative myocardial collagen content. RESULTS: The volume at which left ventricular pressure reached 30 mm Hg was not significantly different between hearts without and with assist device support for less than 40 days. However, the volume at which left ventricular pressure reached 30 mm Hg in patients with assist devices supported for more than 40 days was significantly smaller than that of the hearts without assist devices but was larger than that of normal hearts. A similar pattern was observed for myocyte diameter. Sarcoplasmic endoreticular calcium adenosine triphosphatase 2a expression increased to normal levels by about 20 days of support with an assist device. Relative collagen content was significantly increased in hearts supported for more than 40 days. CONCLUSION: Maximum structural reverse remodeling by left ventricular assist devices is complete by about 40 days. Molecular reverse remodeling of sarcoplasmic endoreticular calcium adenosine triphosphatase 2a expression is quicker, being complete by about 20 days.     

Left ventricular function during support with an asynchronous pulsatile left ventricular assist device.

BACKGROUND: Left ventricular assist devices (LVADs) are frequently used to maintain patients with severe heart failure until heart transplantation becomes possible. Some patients may experience recovery of LV function during such support. Therefore, it is essential to be able to monitor changes in LV function in this setting. METHODS: We studied LV function in 10 patients (median age 34 years, 9 male) who had LVADs implanted because of severe heart failure due to dilated cardiomyopathy a median of 4 months previously. Median pre-implant ejection fraction was 27% and all patients had been on maximal medical therapy, including intravenous inotropic support, prior to insertion of the LVAD. RESULTS: During LVAD support there were cyclical variations in LV dimensions, fractional shortening (FS) and transmitral flow, related to changes in the phase relationship of the LV and the LVAD. The "best" FS occurred when LV systole coincided with device filling and the "worst" FS when LV systole coincided with device ejection. Median FS with the pump switched off was 18% (10% to 32%). Pump-off FS was significantly greater than the "worst" FS with the pump on (5%, p = 0.002), and similar to the "best" pump-on FS (19%, p = NS). CONCLUSIONS: LV function could be studied echocardiographically during LV support and brief periods of interruption in support. Function varied according to the phase relationship of the LV and LVAD. The "best" FS measured during LVAD support was more closely related to the FS with the device switched off than the "worst" pump on FS. The "best" pump-on LV function is therefore most representative of intrinsic LV performance and can be used as a guide to recovery and the potential need for pump-off studies.     

Endotoxaemia during left ventricular assist device insertion

Editor—We read with interest the excellent article byDr O’Malley and colleagues on 12 left ventricular assistdevice (LVAD) insertion patients, describing the associationbetween endotoxaemia     

Myocardium-sparing cannulation technique for left ventricular assist device support

The left atrium and the left ventricular apex are the most commonly used sites of inflow cannulation for postcardiotomy left ventricular support. A new cannulation technique that requires only an ascending aortotomy is introduced. This procedure can be undertaken with equipment present in any cardiac operating room and may prove to cause fewer complications than conventional cannulation techniques.     

Evaluation of myocardial function in patients with end-stage heart failure during support with the Jarvik 2000 left ventricular assist device.

In 2 patients with the Jarvik 2000 left ventricular assist device (LVAD), we assessed left ventricular systolic function through pressure-volume loops and E(max) at the beginning and end of the support period to potentially predict the possibility of pump removal without transplantation. Immediately before LVAD implantation and explantation, pressure and volume measurements were made with catheters and echocardiography, respectively, the E(max) being calculated from the slope of the pressure-volume loops, and the left ventricular ejection fraction (LVEF) being estimated by echocardiography. Transplantation was performed after 14 and 62 days, respectively, during which the LVEF increased by 75% (from 12% to 21%) in Patient 1 and remained unchanged (from 16% to 18%) in Patient 2, whereas the E(max) increased from 0.63 and 0.42 mm Hg/ml, respectively, to 1.31 and 1.07 mm Hg/ml, reflecting a 107% and 155% improvement. In these 2 cases, the E(max) was a more reliable indicator of intrinsic myocardial contractility than was the LVEF.     

Transcatheter closure of patent foramen ovale for hypoxemia during left ventricular assist device support.

A patent foramen ovale with right-to-left shunting was responsible, in part, for profound hypoxemia in a patient who required mechanical support with a left ventricular assist device for cardiogenic shock. The patent foramen ovale was detected with contrast transesophageal echocardiography, and the defect was closed successfully with a transcatheter septal defect closure device.     

Impact of pretransplant left ventricular assist device support duration on outcome after heart transplantation

 Open in a separate windowOBJECTIVESHeart transplantation after left ventricular assist device (LVAD) implantation remains challenging. It is still unclear whether its support duration impacts the outcome after transplantation. METHODSAll patients undergoing heart transplantation between 2010 and 2021 at a single department after previous left ventricular assistance were retrospectively reviewed and divided into 4 different study groups with regard to the duration of LVAD support to examine the impact on the postoperative morbidity and mortality.RESULTSA total of n = 198 patients were included and assigned to the 4 study groups (group 1: <90 days, n = 14; group 2: 90 days to 1 year, n = 31; group 3: 1–2 years, n = 29; group 4: >2 years, n = 24). Although there were no differences between the 4 groups concerning relevant mismatch between the recipients and donors, the incidence of primary graft dysfunction was numerically increased in patients with the shortest support duration, and also those patients with >1 year of support (group 1: 35.7%, group 2: 25.8%, group 3: 41.4%, group 4: 37.5%, P = 0.63). The incidence of acute graft rejection was by trend increased in patients of group 1 (group 1: 28.6%, group 2: 3.3%, group 3: 7.1%, group 4: 12.5%, P = 0.06). Duration of LVAD support did not impact on perioperative adverse events (infections, P = 0.79; acute kidney injury, P = 0.85; neurological events, P = 0.74; thoracic bleeding, P = 0.61), neither on postoperative survival (1-year survival: group 1: 78.6%, group 2: 66.7%, group 3: 80.0%, group 4: 72.7%, P = 0.74).CONCLUSIONWe cannot identify a significant impact of the duration of pretransplant LVAD support on postoperative outcome; therefore, we cannot recommend a certain timeframe for transplantation of LVAD patients.     

Disease-specific remodeling of cardiac mitochondria after a left ventricular assist device

BACKGROUND: Failing hearts can exhibit elements of structural and molecular "reverse remodeling" after support with a left ventricular assist device (LVAD). The present study examined LVAD-induced remodeling of cardiac mitochondria. METHODS: Left ventricular tissue from 20 failing and 21 LVAD-supported hearts, catagorized as ischemic (ICM) or dilated (DCM) cardiomyopathy and four nonfailing hearts were studied. Myocyte mitochondrial ultrastructure was assessed by high-performance liquid chromatography determination of cardiolipin, a specific lipid component of the inner membrane, and its three major molecular species: L4, L3O, and L2O2. RESULTS: Both failing and LVAD-supported hearts exhibited a reduction in cardiolipin content that was independent of the type of cardiomyopathy. However, in failing/ICM hearts, there was a 25% increase in the L4/L3O ratio and a 70% increase in the L4/L2O2 ratio, indicating a change in cardiolipin composition. These alterations were normalized by LVAD support. In sharp contrast, molecular species ratios in DCM hearts were the same as those in nonfailing hearts regardless of whether LVAD support had been used or not. CONCLUSIONS: These data demonstrate LVAD-induced reverse remodeling of myocyte cardiolipin composition in ICM but not DCM hearts.     

Left ventricular pressure and volume unloading during pulsatile versus nonpulsatile left ventricular assist device support

BACKGROUND: Nonpulsatile axial or centrifugal pumps are the latest generation of left ventricular assist devices (LVAD). Whether left ventricular (LV) unloading and outcome in these devices is similar to pulsatile LVADs during long-term support has not been investigated. We compared LV unloading and mortality between different types of LVAD support (pulsatile versus nonpulsatile). METHODS: In 31 patients undergoing long-term LVAD implantation (nonpulsatile = 10, pulsatile = 21) preoperative and postoperative echocardiographic and hemodynamic assessment with right heart catheterization had been obtained. RESULTS: All patients had similar echocardiographic, hemodynamic, and clinical heart failure characteristics at baseline. The degree of LV pressure unloading was the same in both device types, caused by similar reduction of mean pulmonary pressure (18.6 +/- 5.1 versus 18.3 +/- 7.5 mm Hg) and pulmonary capillary wedge pressure (8.9 +/- 4.4 versus 8.0 +/- 7.0 mm Hg). Left ventricular volume unloading was pronounced with a pulsatile device owing to a statistically significant higher pump output (5.1 +/- 1.0 L/min) in comparison with nonpulsatile LVADs (3.6 +/- 0.9 L/min, p < 0.001). Echocardiographic-determined end-systolic indicators confirm this augmentation in pulsatile LVADs. Etiology or the time interval of hemodynamic reassessment had no impact in left ventricular pressure unloading, but LV volume unloading decreased between day 60 and 120 in patients with nonpulsatile LVADs. The preoperative and postoperative transplant mortality was comparable in both groups. CONCLUSIONS: Left ventricular pressure unloading is similar in patients with nonpulsatile as compared with pulsatile implantable long-term assist devices. Left ventricular volume unloading is pronounced in pulsatile LVADs.     

Cardiac resurrection after bone-marrow-derived mononuclear cell transplantation during left ventricular assist device support

We describe a novel therapy of mononuclear cell transplantation combined with a left ventricular assist device (LVAD) for severe ischemic heart failure. Significant myocardial recovery by the LVAD rarely occurs in the severely failing heart. We undertook successful mononuclear cell transplantation in a patient who sustained an acute myocardial infarction that had resulted in the LVAD therapy. The heart regained good function after cell transplantation, and the LVAD was explanted 6 weeks later. These results suggest that this novel therapy could be an alternative to cardiac transplantation for severe ischemic heart failure.