Stulak, John M.

Pump thrombosis is a major adverse event in patients supported on continuous-flow left ventricular assist devices (CF-LVAD). The aim of this systematic review and meta-analysis was to determine the outcomes of various treatment approaches for pump thrombosis, including surgical as compared to medical therapy. Electronic search was performed to identify all studies in the English literature addressing surgical and medical management of pump thrombosis in the modern CF-LVAD era. All identified articles were systematically assessed for inclusion and exclusion criteria. In the meta-analysis, because of significant overlap of the data, reports based on trials, registries, and individual cohort studies were analyzed separately. Forty-three studies were included in the analysis (2 trials, 4 registry reports, and 37 individual cohort studies). 2,281/28,728 (10.6%) patients developed pump thrombosis, of which 44.4% and 55.1% were supported on the HeartWare and HeartMate II, respectively. To avoid overlap in studies and to seek more granular data, pooled individual cohort studies were found to be representative of the entire population, and further in-depth analysis of this category was performed. Of the 610/5,545 (11.8%) patients with pump thrombosis in these individual cohort studies, 225 patients had surgical pump exchange, and 186 were treated medically. Surgical therapy resulted in higher success as compared to medical therapy (81.3% vs. 45.4%; p < 0.001), lower 30 day mortality rate (16.7% vs. 34.5%; p = 0.013) and recurrence rate (11.8% vs. 38.3%; p < 0.001). Meta-regression of all studies demonstrates a possible temporal increase of pump thrombosis rate (p = 0.040). Surgical pump exchange is superior to medical therapy with a higher success rate of pump thrombosis resolution, lower mortality rate, and lower recurrence rate. Randomized controlled prospective studies are needed to compare these clinical approaches and their resultant outcomes to guide decision-making for the management of CF-LVAD thrombosis.

Abstract Aims Type 2 diabetes (T2D) is strongly associated with cardiovascular morbidity and mortality in patients. Vascular large conductance Ca2+-activated potassium (BK) channels, composed of four pore-forming α subunits (BK-α), and four regulatory β1 subunits (BK-β1), are densely expressed in coronary arterial smooth muscle cells (SMCs) and play an important role in regulating vascular tone and myocardial perfusion. However, the role of BK channels in coronary microvascular dysfunction of human subjects with diabetes is unclear. In this study, we examined BK channel function and protein expression, and BK channel-mediated vasodilation in freshly isolated coronary arterioles from T2D patients. Methods and results Atrial tissues were obtained from 16 patients with T2D and 25 matched non-diabetic subjects during cardiopulmonary bypass procedure. Microvessel videomicroscopy and immunoblot analysis were performed in freshly dissected coronary arterioles and inside-out single BK channel currents was recorded in enzymatically isolated coronary arteriolar SMCs. We found that BK channel sensitivity to physiological Ca2+ concentration and voltage was downregulated in the coronary arteriolar SMCs of diabetic patients, compared with non-diabetic controls. BK channel kinetics analysis revealed that there was significant shortening of the mean open time and prolongation of the mean closed time in diabetic patients, resulting in a remarkable reduction of the channel open probability. Functional studies showed that BK channel activation by dehydrosoyasaponin-1 was diminished and that BK channel-mediated vasodilation in response to shear stress was impaired in diabetic coronary arterioles. Immunoblot experiments confirmed that the protein expressions of BK-α and BK-β1 subunits were significantly downregulated, but the ratio of BK-α/BK-β1 was unchanged in the coronary arterioles of T2D patients. Conclusions Our results demonstrated for the first time that BK channel function and BK channel-mediated vasodilation were abnormal in the coronary microvasculature of diabetic patients, due to decreased protein expression and altered intrinsic properties of BK channels.

Left ventricular assist device (LVAD) pump thrombosis occurs in up to 8.4% of patients within 3-months postimplantation. Thromboelastography (TEG) could be used to signal hypercoagulability at LVAD implantation to predict patients at high risk for thrombosis. We sought to evaluate whether TEG maximum amplitude (MA) hypercoagulability (MA ≥69 mm) at the time of LVAD implantation predicts pump thrombosis. A single center, retrospective, nested case–control study was conducted using patients from January 1, 2005, to March 31, 2015. Each pump thrombosis case was matched to two control subjects based on age ± 5 years, sex, and duration of follow-up. A multivariable logistic regression analysis was performed on the matched sets; the odds ratio with 95% confidence interval (CI) was calculated to estimate the relative risk. Thirty-seven age- and sex-matched case–control sets were included for a total of 111 study participants. TEG-MA hypercoagulability occurred in 10.8% of the case group versus 6.8% of controls. There was no association between TEG-MA hypercoagulability and device thrombosis (odds ratio 1.71, 95% confidence interval 0.42–7.05, p = 0.46). Utilization of baseline TEG-MA hypercoagulability to detect individuals at risk for LVAD thrombosis is a novel concept. This study found no significant association between TEG-MA and LVAD thrombosis.

The gold standard for noninvasive blood pressure (BP) measurement, the Doppler technique, does not provide systolic blood pressure (SBP) and diastolic blood pressure (DBP) and may limit therapy outcomes. To improve patient care, we tested specifically designed experimental BP (ExpBP) monitor and the Doppler technique by comparing noninvasive measures to the intraarterial (I-A) BP in 31 patients with end-stage heart failure (4 females) 2.6 ± 3.4 days post-LVAD implantation (20 HeartMate II and 11 HeartWare). Bland–Altman plots revealed that the ExpBP monitor overestimated mean arterial pressure (MAP) by 1.2 (4.8) mm Hg (mean difference [standard deviation]), whereas the Doppler by 6.7 (5.8) mm Hg. The ExpBP SBP was overestimated by 0.8 (6.1) mm Hg and DBP by 1.9 (5.3) mm Hg compared with the respective I-A pressures. Both techniques achieved similar measurement reliability. In the measurement “success rate” expressed as a frequency (percent) of readable BP values per measurement attempts, Doppler accomplished 100% vs. 97%, 97%, and 94% of successful detections of MAP, SBP, and DBP provided by the ExpBP monitor. The ExpBP monitor demonstrated higher accuracy in the MAP assessment than the Doppler in addition to providing SBP and DBP in majority of subjects. Improved BP control may help to mitigate related neurologic adverse event rates.

Background and aim Thoracic radiation therapy (XRT) for cancer is associated with the development of significant coronary artery disease that may require coronary artery bypass grafting surgery (CABG). Contemporary acute surgical outcomes and long-term postoperative survival of patients with prior XRT have not been well characterised. Methods This was a retrospective, single-centre study of patients with a history of thoracic XRT who required CABG and who were propensity matched against 141 controls who underwent CABG over the same time period. The objectives were to assess early CABG outcomes and long-term survival in patients with prior XRT. Results Thirty-eight patients with a history of previous thoracic XRT underwent CABG from 1994 to 2013. The median time from XRT exposure to surgery was 7.9 years (IQR: 2.5–18.4 years). Perioperative adverse events were similar in the XRT group and controls; however, there was a trends lower utilisation of internal mammary artery (IMA) grafts in the XRT group (89%vs98%, P=0.13). After a median postoperative follow-up of 5.4 years (IQR 0.9–9.4 years), no difference in long-term all-cause mortality was observed. Conclusion Patients with prior thoracic XRT who undergo CABG have similar long-term all-cause mortality compared with controls. Isolated CABG after thoracic XRT is not associated with higher perioperative complications, but IMA graft use may be limited by prior XRT.

Objective Female sex is a known risk factor for cardiac surgery, and tricuspid valve (TV) disease is more common in women. There are few data on sex-stratified surgical outcomes for isolated TV surgery. An administrative database was used to compare acute in-hospital outcomes between men and women undergoing isolated TV surgery. Methods Patients aged >18 who underwent TV repair or replacement from 2004 to 2013 were identified using the National Inpatient Sample. Patients were excluded if they had congenital heart disease, endocarditis, or were undergoing concomitant cardiac surgeries except coronary bypass. Results were weighted to represent national averages. Sex-stratified analysis was performed using propensity score matching to compare in-hospital mortality, postoperative complications and hospital costs. Results Over 10 years, women represented 58% of the 5005 TV surgeries performed. With propensity matching, hospital mortality (7.9% vs 7.7%; P=0.99) and median length of stay (11 vs 11 days; P=0.99) were similar between men and women. However, median hospital charges were higher for men ($166 000 vs $155 000; P=0.04). Conclusion Isolated TV surgery is rare, but women more commonly undergo the procedure. In-hospital mortality was similar between men and women after propensity matching, but remains markedly high for both men and women in comparison to that reported for left-sided isolated valve surgery.

Cross-linked hemoglobin (XL-Hb) infused into dogs increases mean arterial pressure (MAP) but decreases blood flow to the renal (RBF), mesenteric (MBF), and iliac (IBF) circulations. These actions differ markedly from dextran infusion (which increases RBF, MBF, and IBF without altering MAP) and may be due to scavenging of nitric oxide by XL-Hb. However, because the hormonal milieu regulating regional circulation is altered during hemorrhage (when XL-Hb may be used), we studied whether systemic hemodynamics, RBF, MBF, IBF, and renal excretory function in hemorrhaged dogs was altered when resuscitated with XL-Hb compared with dextran ( n = 6 each). Hemorrhage decreased MAP by 25% due to a 75% decline in cardiac output. RBF, MBF, and IBF all fell by 33, 64, and 72%, respectively ( P < 0.05 each). There was also a fall in glomerular filtration rate (GFR), urinary flow, and sodium excretion ( P < 0.05 each). After resuscitation, MAP, cardiac output, RBF, MBF, IBF, and GFR all recovered to basal values with either XL-Hb or dextran. Urinary flow and sodium excretion increased to above basal levels with dextran (both by 3.5-fold; P < 0.05) or XL-Hb (by 7.5- and 10-fold, respectively; P < 0.05). We conclude that resuscitation with XL-Hb after hemorrhage not only increases MAP, but also restores RBF, MBF, IBF, GFR, and urinary sodium and volume excretion analogously to dextran. The results contrast with those in normal dogs and suggest that nitric oxide inhibition does not impair hemodynamic and renal function recovery during hemorrhage.

It is well known that hemoglobin binds nitric oxide (NO) and produces a pronounced vasoconstriction in isolated arteries. However, it is debatable whether such an effect takes place in whole animals, because hemoglobin also catalyzes the formation of prostaglandins from arachidonic acid. Short-term studies were performed to evaluate the effects induced by intravenous infusion of cross-linked hemoglobin (XL-Hb) on blood pressure (BP) and renal, iliac, and mesenteric flows, and on renal function in six anesthetized dogs. A similar volume-matched expansion with 6% dextran was used as a control (n = 6). Glomerular filtration rate (GFR), urinary flow, and total and fractional sodium excretion were measured before and after XL-Hb or dextran infusion to evaluate possible renal function changes. XL-Hb administration resulted in a 29% elevation in BP and a significant decrease of blood flow (30-37%) to the three vascular beds. XL-Hb did not alter GFR or sodium excretion, despite the increase in BP. In contrast, the administration of dextran did not significantly alter BP but induced a significant increase (6-13%) of blood flow in the three vascular beds. These changes were accompanied by threefold increases in urinary flow and sodium excretion without alterations in GFR. The binding effect of XL-Hb on NO was studied in isolated renal arteries in organ chambers. These in vitro studies showed that XL-Hb blunted the endothelium-mediated vasodilator response to calcium ionophore A-23187 and to acetylcholine. Our results demonstrate that XL-Hb administration is followed by hypertension, vasoconstriction, and blunted natriuresis. All these effects are compatible with the scavenging effect on NO attributed to XL-Hb.

Background Diabetes mellitus (DM) is a risk factor for morbidity and mortality in patients with heart failure. The effect of DM on post–left ventricular assist device (LVAD) implantation outcomes is unclear. This study sought to investigate whether patients with DM had worse outcomes than patients without DM after LVAD implantation and whether LVAD support resulted in a better control of DM. Methods and Results We retrospectively reviewed 341 consecutive adults who underwent implantation of LVAD from 2007 to 2016. Patient characteristics and adverse events were studied and compared between patients with and without DM. One hundred thirty-one patients (38%) had DM. Compared with patients without DM, those with DM had higher rates of ischemic cardiomyopathy, LVAD implantation as destination therapy, and increased baseline body mass index. In a proportional hazards (Cox) model with adjustment for relevant covariates and median follow-up of 16.1 months, DM was associated with increased risk of all-cause mortality (hazard ratio, 1.73; 95% confidence interval: 1.18–2.53; P =0.005) and increased risk of nonfatal LVAD-related complications, including a composite of stroke, pump thrombosis, and device infection (hazard ratio, 2.1; 95% confidence interval: 1.35–3.18; P =0.001). Preoperative hemoglobin A1c was not significantly associated with mortality or adverse events among patients with DM. LVAD implantation resulted in a remarkable decrease in hemoglobin A1c levels (7.4±1.9 pre-LVAD versus 6.0±1.5 and 6.3±1.4 after 3 and 12 months post-LVAD, respectively; P <0.0001) and a significant reduction in requirements of DM medications. Conclusions DM is associated with increased rates of all-cause mortality and major adverse events despite favorable glycemic control after LVAD implantation.