Syndrome in a Patient with Mechanical Circulatory Support


Study


MCS type


N=


Pre-implantation renal function


Follow up


Post-implantation renal function


Conclusion


Sandner SE, et al. Ann Thorac Surg. 2009;87(4):1072–8.


CF


86


Group with eGFR > 60 mL/min/1.73 m 2


BUN: 21 ± 7 mg/dL


Cr: 1.0 ± 0.1 mg/dL


Group with eGFR < 60 mL/min/1.73 m 2


BUN: 44 ± 20 mg/dL


Cr: 1.6 ± 0.4 mg/dL


1, 3 and 6 months


Patients with eGFR <60 mL/min/1.73 m2 manifested an overall improvement of eGFR from implant to 1,3 and 6 months


Patients with eGFR >60 mL/min/1.73 m2 exhibited only an early improvement of eGFR from implant to month 1


Renal function improves after LVAD implantation


Russell SD, et al. Circulation. 2009;120(23):2352–7


CF


309


BUN: 29 ± 16 mg/dL


Cr: 1.4 ± 0.5 mg/dL


1, 3, 5, 7, 11, 14, and 21 days


1 to 6 months


After a slight early increase in Cr, renal function improved in patients with kidney dysfunction, stabilizing by approximately 1–2 months of LVAD support. No significant changes in patients with normal kidney function


LVAD improves renal function in patients with baseline dysfunction and does not impair renal function in patients with normal renal function at baselines


Hasin T, et al. J Am Coll Cardiol. 2012;59(1):26–36


CF


83


eGFR: 53 ± 21 mL/min/1.73 m2


1, 3 and 6 months


eGFR increased significantly at 1 month and remained above pre-LVAD values at 3 and 6 months


Renal dysfunction is reversible and probably related to poor renal perfusion


Kirklin JK, et al. J Heart Lung Transplant. 2013;32(12):1205–13


CF


4917


Mild or no renal dysfunction (n = 3160)


Moderate renal dysfunction (n = 1475)


Severe renal dysfunction (n = 282)


1 week, 1, 3, 6, 12, 18, and 24 months


Surviving patients manifested significant improvements in renal function parameters within 1 month, which remained stable afterwards


Renal function improves early after LVAD implantation


Gupta S, et al. Heart, Lung & Circulation. 2014;23(10):963–9


CF


53


Cr: 109 ± 43 μmol/L


3 months


Cr decreased significantly


LVAD support improves renal function


Deo SV, et al. Heart, Lung & Circulation. 2014;23(3):229–33


CF


126


BUN: 27 [20–40] mg/dL


Cr: 1.4 [1.2–1.9] mg/dL


eGFR: 52 ± 20 mL/min/1.73 m2


1, 6 and 12 months


After an initial reduction of Cr at 1 month, a gradual increase was noted over the study period


Renal function exhibits early improvement and then remains stable


Raichlin E, et al. ASAIO Journal. 2016;62(3):261–7


CF


165


BUN: 23 ± 10 mg/dL


Cr: 1.3 ± 0.5 mg/dL


eGFR: 64 ± 24 mL/min/1.73 m2


1, 3, and 6 months


1 year


Patients with eGFR >40 mL/min/1.73 m2 exhibited a significant early eGFR increase at 1 month and then a gradual decrease (1 year follow-up eGFR did not differ significantly from the pre-LVAD level).


Patients with eGFR ≤40 mL/min/1.73 m2 demonstrated significant early renal function improvement after 1 and 3 months, followed by stable eGFR values


Renal function in patients with eGFR ≤40 mL/min/1.73 m2 benefit from LVAD support


Yoshioka D, et al. Ann Thorac Surg. 2017;103(3):717–24


CF


469


BUN: 37 ± 18 mg/dL


Cr: 1.5 ± 0.6 mg/dL


eGFR:58 ± 28 mL/min/1.73 m2


1 and 6 months


1, 2 and 3 years


Renal function was significantly improved 1 month after LVAD implantation and gradually declined thereafter


LVAD improves renal function transiently with return to baseline after prolonged support


Brisco MA, et al. Circ Heart Fail. 2014;7(1):68–75


PF/CF


3363


Cr: 1.5 ± 0.8 mg/dL


eGFR: 60 ± 35 mL/min/1.73 m2


1 week


1, 3, and 6 months


1 year


eGFR improved transiently and by 1 year, it was only slightly above the pre-LVAD value


Early improvement in renal function after LVAD support is probably transient


Khot UN, et al. J Am Coll Cardiol. 2003;41(3):381–5


PF


18


Cr: 4.0 ± 0.7 mg/dL


VAD placement, transplantation, 1, 3, and 6 months post-transplantation


Renal function improvement


In severe renal insufficiency complicating cardiogenic shock, early mechanical support with VAD resulted in long-term recovery of renal function


Butler J, et al. Ann Thorac Surg. 2006;81(5):1745–51


PF


220


BUN: 35 ± 21 mg/dL


Cr: 1.5 ± 0.8 mg/dL


CrCl: 77 ± 46 mL/min


1–4 weeks


CrCl improvement


Renal function improves with LVAD use


Singh M, et al. Ann Thorac Surg. 2011;91(5):1348–54


PF/CF (BiVAD/LVAD)


116


CrCl: 58 mL/min pre-MCS


CrCl: 70 mL/min pre-transplantation


2 weeks +1, 3, and 6 months post-MCS


Pre-transplantation


2 weeks +1, 3, 6, and 12 months post-transplantation


Significant early improvement in CrCl, no further improvement beyond 1 month. After transplantation worsening renal function that was most pronounced after 2 weeks


MCS use leads to improvements in renal function



BiVADs biventricular ventricular assist device, BUN blood urea nitrogen, CF continuous flow, Cr creatinine, CrCl creatinine clearance, eGFR estimated glomerular filtration rate, MCS mechanical circulatory support, PF pulsatile flow, VAD ventricular assist device




Hasin et al., in a retrospective study of 83 consecutive patients who underwent continuous flow LVAD implantation, monitored the estimated GFR on admission and during follow-up (after 1, 3, and 6 months) and reported a significant improvement of renal function [40]. Furthermore, the authors reported that an increase in estimated GFR (from 40 ± 12 to 55 ± 18 mL/min/1.73 m2) with optimal medical treatment before surgery was found to be a positive prognostic marker of improved renal function after LVAD implantation. Gupta et al. retrospectively reviewed 53 consecutive patients who received a HeartWare centrifugal continuous flow LVAD implantation [42]. They reported a significant decrease of creatinine values compared to baseline at 3 months post-implantation (p < 0.001).


Brisco et al. examined 3363 patients with MCS from the INTERMACS registry and reported a post-MCS early (during the first month) significant improvement of the estimated GFR (median improvement, 49%; p < 0.001) [43] compared to baseline values. However, this improvement after the first month, continued as a descending trajectory for up to 1 year of follow-up (median improvement, 7%; p < 0.001). Moreover, the investigators highlighted the adverse survival in patients who demonstrated substantial early or late changes in renal function (whether improvements or worsening). Russell et al. examined 309 advanced heart failure patients undergoing LVAD implantation as a BTT and analysed the effects of HeartMate II on renal and hepatic function [44]. The population enrolled in the study was divided into two groups based upon the pre-implantation renal (creatinine and blood urea nitrogen) and hepatic (aspartate transaminase, alanine transaminase, and total bilirubin) laboratory values. A significant improvement with time (up to 6 months) was observed in the group with abnormal values at baseline, whereas laboratory values remained unchanged in those with normal values at baseline. Another interesting study investigated the long-term effects of continuous flow LVAD devices on hepatic and renal function of advanced heart failure patients [45]. Regarding the entire cohort, the authors reported a significant decrease of serum creatinine at 1-month post-implantation (p < 0.0001) followed by a gradual increase over 1 year (p = 0.0038 from 1 to 6 months and p = 0.05 from 6 to 12 months). On the contrary, serum bilirubin demonstrated a descending trajectory throughout the study. Creatinine values at 1 year were significantly lower compared to the pre-procedure values (p = 0.0003). Regarding the high-risk cohort (defined as serum creatinine >1.9 mg/dL or serum bilirubin >1.5 mg/dL), the researchers observed a significant drop in creatinine at the end of 1-month follow-up (p < 0.0005) followed by a further decrease until 6 months (p = 0.01) and a stable course until the end of the study (1 year). Similarly to the entire cohort, the 1-year creatinine levels were significantly lower compared to the baseline values (p = 0.0005). The long-term effects of continuous flow LVADs on renal and hepatic function were also the scope of the study by Yoshioka et al. [46]. Regarding the subgroup of patients with pre-procedural estimated GFR <60 mL/min/1.73 m2, the initial estimated GFR increase 1-month post-implantation (p < 0.05 versus pre-operative values) was followed by a gradual estimated GFR decrease resulting in values comparable to baseline after 3 years. On the contrary, hepatic function (transaminases, bilirubin, MELD-IX score) remained normal in LVAD patients during the 3 years of follow-up. Raichlin et al., in a series of 165 consecutive heart failure patients who received HeartMate II LVADs, reported that patients with baseline estimated GFR >40 mL/min/1.73 m2 (n = 135) exhibited a significant estimated GFR increase during the first month after implantation and subsequently a gradual decrease, resulting in 1-year follow-up values similar to those manifested before the operation, whereas patients with baseline estimated GFR ≤40 ml/min/1.73 m2 (n = 30) demonstrated significant renal function improvement at 1 and 3 months, followed by stable estimated GFR values, albeit higher compared to the pre-procedural ones, until 1 year post-implantation [47]. Taken all together, although the use of LVADs is accompanied by favourable short-term improvements in renal function, there is uncertainty about the long-terms impact.


Acute Kidney Injury and Left Ventricular Assist Devices


A number of criteria have been proposed for the definition of acute kidney injury (AKI) [48]. According to the most recent Kidney Disease: Improving Global Outcomes (KDIGO) criteria, AKI is defined as any of the following: (a) Increase in serum creatinine by ≥0.3 mg/dL (≥26.5 μmol/l) within 48 h; or (b) Increase in serum creatinine to ≥1.5 times its baseline, which is known or presumed to have occurred within the prior 7 days; or (c) Urine volume < 0.5 mL/kg/h for 6 h [49]. Interestingly, WRF is usually defined as a serum creatinine increase of ≥0.3 mg/dL compared to the admission value [30]. A recent study defined WRF as a change in serum creatinine ≥0.3 mg/dL during the first 5 days after admission [50].


Several pre-operative factors (serum creatinine >1.5 mg/dL, impaired right ventricular function, high CVP, older age, higher LVAD score, INTERMACS score 1 or 2, low albumin and total protein, low left ventricular end-diastolic diameters, kidney size <10 cm, use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers), intra-operative factors (longer cardiopulmonary bypass time, number of blood transfusions, bleeding >1 L), and post-operative factors (need for reoperation within 48 h, intra-aortic balloon pump, liver dysfunction, sepsis) have been associated with the development of AKI post-operatively [51, 52]. The aetiology for the development of AKI in LVAD patients is multifactorial and includes pre-renal (hypovolemia, heart failure exacerbation, cardiogenic shock, sepsis, renal arterial disease and drugs such as non-steroidal anti-inflammatory drugs or angiotensin-converting enzyme inhibitors), intrinsic renal (hemolysis, sepsis) and post-renal causes (tumors, stones, hematoma) [53]. However, a recent study has challenged the traditional perspective which perceives AKI in advanced heart failure patients as the result of reduced renal perfusion [54]. The authors examined 575 heart failure patients from the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) and investigated the association between their cardiac index and estimated GFR. They found an inverse correlation between the cardiac index and the estimated GFR (r = −0.12; p = 0.02) and no association between the cardiac index and the blood urea nitrogen or the blood urea nitrogen to creatinine ratio. Therefore, the authors concluded that impaired cardiac output is not the leading cause of renal dysfunction in patients with advanced heart failure.


Acute kidney injury is a frequent finding in advanced heart failure patients after LVAD implantation. The incidence of AKI post-LVAD implantation ranges from 7% to 56%, and it is accompanied by high short- and long-term mortality rates ranging from 57% to 93% [55]. The large variation in AKI incidence may be due to different definitions used for AKI, the baseline severity of heart failure (INTERMACS level), and the incidence and severity of pre-implantation CKD [50]. Alba et al. observed a significantly lower short-term survival rate at 15, 30, 90 and 130 days post-implantation (p < 0.01) in the group of patients who manifested AKI as defined by the RIFLE criteria [56] after LVAD implantation [57]. Another interesting study revealed the close inverse association between AKI (defined as renal failure requiring renal replacement therapy) and the 6-month survival for patients treated with an MCS as a BTT (p < 0.01) [58]. Regarding long-term outcomes, Topkara et al. followed retrospectively 201 patients who received LVADs, between 1996 and 2004, and reported that those who needed continuous veno-venous haemodialysis due to severe AKI manifested significantly worse survival rates at 1, 3, 5 and 7 years compared to those who did not (p < 0.001) [59]. Genovese et al. retrospectively analysed the early adverse outcomes and their association with 1-year mortality, in a series of 163 advanced heart failure patients who underwent MCS device implantation (LVADs or biventricular assist devices) between 1996 and 2008 and concluded that AKI (defined as abnormal kidney function requiring renal replacement therapy in patients who did not require this procedure before implant or a rise in serum creatinine >3 times normal baseline values or > 5 mg/dL) was the only significant and independent predictor of increased 1-year mortality. In particular, patients exhibiting AKI early after MCS device implantation manifested a three-fold increased risk of death during the first year after the procedure [60]. Similarly, Aik et al. examined the relationship between risk factors and adverse outcomes in 157 patients who received MCS. The investigators reported that AKI (defined as a ≥ 50% increase in serum creatinine over the first 7 post-procedure days) was a significant predictor of 30-day and 365-day mortality. An interesting study examined the natural history of heart failure patients who developed severe renal failure after continuous flow LVAD implantation requiring renal replacement therapy either by continuous veno-venous hemofiltration dialysis (CVVHD) or hemodialysis, or both [61]. The investigators observed that patients who recovered from the operation and showed clinical improvement (New York Heart Association functional class I), managed to wean from the renal replacement therapy successfully. In conclusion, AKI not infrequently occurs after LVAD implantation and it is an independent risk factor of adverse short- and long-term prognosis.


Different Types of Mechanical Circulatory Support and Renal Function


The impact of different types of MCS devices on renal function is a conundrum (Table 16.2). For example, Welp et al. examined prospectively the impact of the LVAD type (pulsatile vs. non-pulsatile) on the plasma renin activity (PRA) and aldosterone levels in 20 advanced heart failure patients undergoing LVAD implantation [62]. The investigators found that the levels of PRA decreased to near normal values after 21 days of support both in pulsatile (EXCOR LVAD) and non-pulsatile (INCOR LVAD) devices. Interestingly, these levels remained stable until the end of the study (day 70). However, the group on pulsatile LVAD exhibited significantly lower PRA compared to the non-pulsatile group after 21 days of support, and this difference remained unchanged until the end of the study. Similar results were found concerning aldosterone levels. In particular, although aldosterone levels significantly dropped after the initial 3 weeks on both types of MCS and remained at near normal levels until day 70, the levels of aldosterone in the pulsatile group was significantly lower compared with the non-pulsatile group after 21 days of LVAD support and this difference didn’t change until the end of the study. Apart from RAAS activation, several other pathophysiological mechanisms have been implicated in the development of renal impairment as the result of chronic non-pulsatile MCS exposure, including smooth muscle cell hypertrophy of renal cortex arteries and kidney peri-arteritis [43, 63, 64]. Nevertheless, it has been reported that even though the pulsatility is low in heart failure patients receiving continuous flow LVADs, the baroreflex sensitivity is preserved [65]. The study by Brisco et al. found no difference regarding the estimated GFR trajectory (significant early improvement followed by a late decline) post-implantation between continuous and pulsatile flow LVAD recipients [43]. Another study compared the renal outcomes of patients receiving continuous versus pulsatile flow LVADs as a BTT [66]. Both groups manifested a significant improvement of renal function (defined by estimated GFR) 1, 4, and 12 weeks post-LVAD implantation. Interestingly, no significant difference was observed as far as post-implantation renal function adverse outcomes between continuous and pulsatile LVADs. Yoshioka et al. showed that perioperative mortality in patients undergoing LVAD implantation depends more on the preoperative GFR than the type of LVAD device used (Nipro LVAD vs. other types of LVADs) [32]. Nadziakiewicz and colleagues compared the effects of continuous (HeartMate II or HeartWare) versus pulsatile (Polvad MEV) LVADs on renal function the first 30 days after implantation [67] and found no significant differences between the two groups [67]. A study examined retrospectively 58 advanced heart failure patients divided into three groups based on the LVAD type that they had received (centrifugal, axial, and pulsatile) [68]. The authors reported a significant improvement of renal function compared to baseline at month 1 and 3 after the LVAD implantation and concluded that centrifugal, axial and pulsatile LVADs provide adequate support on end-organ function in advanced heart failure patients. On the contrary, Slaughter et al. enrolled, in a randomized manner, 134 and 66 patients who underwent continuous and pulsatile flow LVADs implantation, respectively [69] and reported a significantly lower rate of renal failure (defined as abnormal kidney function requiring renal replacement therapy in patients who did not require this procedure prior to implant) in advanced heart failure patients receiving continuous flow LVADs in comparison to those who had received pulsatile flow LVADs (p < 0.001). Notably, this study demonstrated no significant difference with respect to adverse hemorrhagic events (hemorrhagic stroke, bleeding requiring packed red blood cells, bleeding requiring surgery). Lastly, Jacobs et al. reported an improvement of renal function 3 months after full (continuous flow LVAD) or partial (Synergy micropump) mechanical support devices implantation [70]. A significant renal improvement was observed in the group of patients with pre-operative impaired renal function (defined as an estimated GFR <60 mL/min/1.73 m2). This study underscores the beneficial effects of the Synergy micropump, a miniaturized LVAD used mostly as partial support in patients with renal dysfunction, 3 months after implantation. In conclusion the results of the above-mentioned studies are inconsistent. However, the evidence derived from the randomized HeartMate II versus HeartMate XVE trial indicates an advantage with continuous flow versus pulsatile flow LVADs with respect to adverse renal events.


Table 16.2

Comparison of different types of mechanical circulatory support (MCS) and their impact on renal function

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Oct 30, 2020 | Posted by in Uncategorized | Comments Off on Syndrome in a Patient with Mechanical Circulatory Support

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