Defining levels of care in cardiogenic shock.

Background: Expert opinion and professional society statements have called for multi-tier care systems for the management of cardiogenic shock (CS). However, little is known about how to pragmatically define centers with different levels of care (LOC) for CS. Methods: Eleven of 23 hospitals within our healthcare system sharing a common electronic health record were classified as different LOC according to their highest mechanical circulatory support (MCS) capabilities: Level 1 (L-1)-durable left ventricular assist device, Level 1A (L-1A)-extracorporeal membrane oxygenation, Level 2 (L-2)-intra-aortic balloon pump and percutaneous ventricular assist device; and Level 3 (L-3)-no MCS. All adult patients treated for CS (International Classification of Diseases, ICD-10 code R57.0) between 2016 and 2022 were included. Etiologies of CS were identified using associated diagnostic codes. Management strategies and outcomes across LOC were compared. Results: Higher LOC centers had higher volumes: L-1 (n = 1): 2,831 patients, L-1A (n = 4): 3,452, L-2 (n = 1): 340, and L-3 (n = 5): 780. Emergency room admissions were more common in lower LOC (96% at L-3 vs. 46% L-1; p < 0.001), while hospital transfers were predominant at higher LOC (40% at L-1 vs. 2.7% at L-3; p < 0.001). Men comprised 61% of the cohort. Patients were younger in the higher LOC [69 (60-78) years at L-1 vs. 77 (67-85) years at L-3; p < 0.001]. Patients with acute myocardial infarction (AMI)-CS and acute heart failure (AHF)-CS were concentrated in higher LOC centers while other etiologies of CS were more common in L-2 and L-3 (p < 0.001). Cardiac arrest on admission was more prevalent in lower LOC centers (L-1: 2.8% vs. L-3: 12.1%; p < 0.001). Patients with AMI-CS received more percutaneous coronary intervention in lower LOC (51% L-2 vs. 29% L-1; p < 0.01) but more coronary arterial bypass graft surgery at higher LOC (L-1: 42% vs. L-1A: 23%; p < 0.001). MCS use was consistent across levels for AMI-CS but was more frequent in higher LOC for AHF-CS patients (L-1: 28% vs. L-2: 10%; p < 0.001). Despite increasing in-hospital mortality with decreasing LOC, no significant difference was seen after multivariable adjustment. Conclusion: This is the first report describing a pragmatic classification of LOC for CS which, based on MCS capabilities, can discriminate between centers with distinct demographics, practice patterns, and outcomes. This classification may serve as the basis for future research and the creation of CS systems of care.

Hemolysis and Nonhemorrhagic Stroke During Venoarterial Extracorporeal Membrane Oxygenation.

BACKGROUND: Hemolysis, even at low levels, activates platelets to create a prothrombotic state and is common during mechanical circulatory support. We examined the association of low-level hemolysis (LLH) and nonhemorrhagic stroke during venoarterial extracorporeal membrane oxygenation (VA ECMO) support. METHODS: A single-center retrospective review of all adult patients placed on VA ECMO from January 2012 to September 2017 was conducted. To determine the association between LLH and nonhemorrhagic stroke, patients were categorized as those with and without LLH. LLH was defined by 48-hour plasma free hemoglobin (PFHb) of 11 to 50 mg/dL after VA ECMO implantation. RESULTS: Of 201 patients who underwent VA ECMO placement, 150 (75%) met inclusion criteria and comprised the study population. They were 55 ± 14 years of age and 50 (33%) were women. Sixty-two (41%) patients had LLH. Patients with LLH had a higher likelihood of incident nonhemorrhagic stroke during VA ECMO support (20 [32%] versus 4 [5%]; adjusted hazard ratio [HR], 7.6; 95% confidence interval [CI], 2.2 to 25.9; p = 0.001). The severity of LLH was associated with an incrementally higher likelihood of a nonhemorrhagic stroke (PFHb 26 to 50 mg/dL: HR, 11.3; 95% CI, 3.6 to 35.1; p = 0.001; PFHb 11 to 25 mg/dL: HR, 4.4; 95% CI, 1.36 to 14.85; p = 0.014) in comparison with no LLH. Those with LLH had a 2-fold greater increase in mean platelet volume after VA ECMO placement (0.98 ± 1.1 fL versus 0.49 ± 0.96 fL; p = 0.03). Patients with a nonhemorrhagic stroke had a higher operative mortality (20 [83%] versus 57 [45%]; adjusted HR, 3.1; 95% CI, 1.8 to 5.3; p < 0.001). CONCLUSIONS: Hemolysis at low levels during VA ECMO support is associated with subsequent nonhemorrhagic stroke.

Seroreversion of positive anti-hepatitis C virus antibodies in left ventricular assist device recipients: Now you see them, now you don't.

The clinical significance of positive anti-hepatitis C virus (anti-HCV) antibody tests in recipients of left ventricular assist devices remains unclear. In light of emerging evidence suggesting the possibility of persistent low-level HCV infection in patients with positive anti-HCV antibody test but negative HCV ribonucleic acid, it is very important to distinguish the truly false positive HCV antibodies, in recipients of continuous flow left ventricular assist devices, from those suggestive of a prior clinically resolved infection or one where a low-level viremia may have persisted. We conducted a retrospective analysis of left ventricular assist device recipients at our institution. While the total incidence of positive HCV antibody with concomitantly negative HCV ribonucleic acid test (19.2%) was in keeping with the incidences reported in prior cross-sectional studies, we longitudinally followed our patients and observed a 100% seroreversion. Seroreversion, which has not been reported in other studies, occurred either during continued left ventricular assist device support (10 out of 26) or after heart transplant (7 out of 26). Hundred percent seroreversion strongly suggested that the anti-HCV antibodies were truly false positive.

Noninvasive Measures of Pulsatility and Blood Pressure During Continuous-Flow Left Ventricular Assist Device Support.

The reliability and validity of a palpable pulse and other noninvasive measures of pulsatility in patients on continuous-flow (CF) left ventricular assist device (LVAD) support have not been rigorously evaluated. We prospectively enrolled 23 patients who had CF-LVAD and an arterial catheter for blood pressure (BP) monitoring. Pulse pressure (PP) via the arterial line was compared with three noninvasive measures of pulsatility: presence of a palpable pulse, pulsatility index (PI), and aortic valve opening (AVO). In addition, the relationship between Doppler BP (DopBP) and arterial line pressures was evaluated. The study group comprised 30% females, 73% nonischemic cardiomyopathy, 87% axial flow device (HeartMate II [HMII]), and 13% centrifugal flow device (HeartWare ventricular assist device [HVAD]) support. Among four practitioners, the interobserver agreement for the presence of a palpable pulse was moderate (k = 0.41; 95% CI, 0.28-0.60). If the PP was ≥15 mm Hg, a radial pulse was palpated 82% of the time, whereas when the PP was <15 mm Hg, a radial pulse was palpated only 35% of the time. In subjects with a palpable pulse, there was a strong correlation between DopBP and systolic BP (SBP) (r = 0.94; 95% CI, 0.82-0.99), whereas the correlation between DopBP and mean arterial pressure (MAP) was much weaker (r = 0.42; 95% CI, 0.19-0.96). In subjects without a palpable pulse, there was a strong correlation between both the DopBP and SBP (r = 0.94; 95% CI, 0.80-1.0) and DopBP and MAP (r = 0.87; 95% CI, 0.77-1.00). Finally, PP was significantly associated with PI (odds ratio [OR], 0.3; 95% CI, 0.14-0.45; p = 0.0002) but not AVO (OR, 1.41: 95% CI, 0.70-2.83; p = 0.33). The presence of a palpable pulse has good interobserver agreement and allows for dichotomization of the DopBP to reflect the SBP in its presence and the MAP in its absence. This simple measure should be incorporated into BP management algorithms for CF-LVADs. The PI shows a modest correlation to PP.

Speed Reduction Does Not Restore High Molecular Weight von Willebrand Multimers During HeartMate II Support: An In Vivo Study.

Acquired von Willebrand Syndrome (AVWS) in patients undergoing continuous-flow left ventricular assist device support is due to the loss of von Willebrand factor (vWF) high molecular weight multimers (HMWMs) by shear-mediated mechanisms. We investigated whether reducing speed in vivo would mitigate the shear effect. In outpatients (n = 6) with a HeartMate II, pump speed was decreased to 8,000 rpm for 6 hours. At baseline (9,140 ± 189 rpm), patients had an AVWS as evidenced by low vWF activity:antigen ratios (0.58 ± 0.13, normal >0.7) and reduced HMWMs. After 6 hours, there was no significant change in either the vWF activity:antigen ratio or the HMWMs. Decreasing pump speed does not ameliorate AVWS.

Sildenafil Is Associated With Reduced Device Thrombosis and Ischemic Stroke Despite Low-Level Hemolysis on Heart Mate II Support.

BACKGROUND: Persistent low-level hemolysis (LLH) during continuous-flow mechanical circulatory support is associated with subsequent thrombosis. Free hemoglobin from ongoing hemolysis scavenges nitric oxide (NO) to create an NO deficiency which can augment platelet function leading to a prothrombotic state. The phosphodiesterase-5 inhibitor, sildenafil, potentiates NO signaling to inhibit platelet function. Accordingly, we investigated the association of sildenafil administration and thrombotic events in patients with LLH during Heart Mate II support. METHODS AND RESULTS: A single-center review of all patients implanted with a Heart Mate II who survived to discharge (n=144). LLH was defined by a discharge lactate dehydrogenase level of 400 to 700 U/L. Patients were categorized as (1) LLH not on sildenafil, (2) LLH on sildenafil, (3) no LLH not on sildenafil, and (4) no LLH on sildenafil. Age, sex, platelet count, and mean platelet volume were similar between groups. Seventeen patients had either device thrombosis or ischemic stroke. Presence of LLH was associated with a greater risk of thrombosis (adjusted hazard ratio, 15; 95% confidence interval, 4.5-50; P<0.001 versus no LLH, not on sildenafil). This risk was reduced in patients with LLH on sildenafil (adjusted hazard ratio, 1.7; 95% confidence interval, 0.2-16.1; P=0.61). Device thrombosis and ischemic stroke were associated with an increase in mean platelet volume (9.6±0.5 to 10.9±0.8 fL, P<0.001). Patients with LLH not on sildenafil had a greater increase in mean platelet volume in comparison to those with LLH on sildenafil (P<0.001). CONCLUSIONS: Sildenafil is associated with reduced device thrombosis and ischemic stroke during ongoing LLH on Heart Mate II support.

Drug-induced torsades de pointes in an underserved urban population. Methadone: is there therapeutic equipoise?

BACKGROUND: Although it has been well established that methadone use can result in prolonged QTc/torsades de pointes (TdP) and has been labeled as one of the main drugs that cause TdP, it is still prescribed indiscriminately, and several cases of methadone-associated TdP have been seen in our community. METHODS: Our objective was to determine the associated factors for prolonged QTc and the development of torsades de pointes (TdP) in our underserved patient population. We found 12,550 ECGs with prolonged QTc between 2002 and 2013. Medical records were reviewed in order to identify precipitating factors for prolonged QTc and to detect incidence of TdP. RESULTS: We identified 2735 patients with prolonged QTc who met the inclusion criteria. Of these, 89 (3%) experienced TdP. There was a greater prevalence of HIV infection in the TdP group (11.2 vs. 3.7%, p < 0.001). Furosemide, hydrochlorothiazide, selective serotonin reuptake inhibitors (SSRIs), amiodarone, ciprofloxacin, methadone, haloperidol, and azithromycin were the drugs most often associated with prolonged QTc (31, 8.2, 7.6, 7.1, 3.9, 3.4 and 3.3%, respectively). However, the agents most commonly associated with TdP were furosemide (39.3%), methadone (27%), SSRIs (19.1%), amiodarone (18%), and dofetilide (9%). The medications with statistical significance in the multivariate analysis for TdP development in descending order were as follows: ranolazine (odds ratios [OR] = 53.61, 95% confidence interval [CI] 5.4-524, p < 0.001), dofetilide (OR = 25, CI 6.47-103.16, p < 0.001), voriconazole (OR = 21.40, CI 3.24-124.25, p < 0.001), verapamil (OR = 10.98, CI 2.62-44.96, p < 0.001), sotalol (OR = 12.72, 1.95-82.81, p = 0.008), methadone (OR = 9.89, CI 4.05-24.15, p < 0.001), and SSRI (OR = 2.26, CI 1.10-5.96, p < 0.001). This multivariate analysis revealed that amiodarone and HIV infection were not implicated in TdP. CONCLUSION: Methadone was by far the leading medication implicated in the development of TdP and an independent predictor in both univariate and multivariate analyses despite the fact that it was not the most common QT-prolonging medication in our population.