UNOS policy change benefits high-priority patients without harming those at low priority.

The heart transplantation policy change (PC) has improved outcomes in high-acuity (Old 1A, New 1-3) patients, but the effect on low-priority (Old 1B/2, New 4-6) patients is unknown. We sought to determine if low-priority patient outcomes were compromised by benefits to high-priority patients by evaluating for interaction between PC and priority status (PS). We included adult first-time heart transplant candidates and recipients from the UNOS registry during a 19-month period before and after the PC. We compared clinical characteristics and performed competing risks and survival analyses stratified by PC and PS. There was a dependence of PC and PS on waitlist death/deterioration with an interaction sub-distribution hazard ratio (adjusted sdHR) of 0.59 (0.45-0.78), p-value < .001. There was a trend toward a benefit of PC on waitlist death/deterioration (adjusted sdHR: 0.86 [0.73-1.01]; p = .07) and an increase in heart transplantation (adjusted sdHR: 1.08 [1.02-1.14], p = .007) for low-priority patients. There was no difference in 1-year post-transplant survival (log-rank p = .22) when stratifying by PC and PS. PC did not negatively affect waitlisted or transplanted low-priority patients. High-priority, post-PC patients had a targeted reduction in waitlist death/deterioration and did not come at the expense of worse post-transplant survival.

Extracorporeal cardiopulmonary resuscitation (ECPR) survival: A quaternary center analysis.

BACKGROUND: Extracorporeal cardiopulmonary resuscitation (ECPR) has emerged as a rescue strategy for nonresponders to conventional CPR (CCPR) in cardiac arrest. Definitive guidelines for ECPR deployment do not exist. Prior studies suggest that arrest rhythm and cardiac origin of arrest may be variables used to assess candidacy for ECPR. AIM: To describe a single-center experience with ECPR and to assess associations between survival and physician-adjudicated origin of arrest and arrest rhythm. METHODS: A retrospective review of all patients who underwent ECPR at a quaternary care center over a 7-year period was performed. Demographic and clinical characteristics were extracted from the medical record and used to adjudicate the origin of cardiac arrest, etiology, rhythm, survival, and outcomes. Univariate analysis was performed to determine the association of patient and arrest characteristics with survival. RESULTS: Between 2010 and 2017, 47 cardiac arrest patients were initiated on extracorporeal membrane oxygenation (ECMO) at the time of active CPR. ECPR patient survival to hospital discharge was 25.5% (n = 12). Twenty-six patients died on ECMO (55.3%) while nine patients (19.1%) survived decannulation but died before discharge. Neither physician-adjudicated arrest rhythm nor underlying origin were significantly associated with survival to discharge, either alone or in combination. Younger age was significantly associated with survival. Nearly all survivors experienced myocardial recovery and left the hospital with a good neurological status. CONCLUSIONS: Arrest rhythm and etiology may be insufficient predictors of survival in ECPR utilization. Further multiinstitutional studies are needed to determine evidenced-based criteria for ECPR deployment.

Cardiac Resynchronization Therapy and Implantable Cardioverter Defibrillator Therapy in Advanced Heart Failure.

Patients with advanced heart failure are at high risk for progression of their disease and sudden cardiac death. The role of device therapy in this patient population continues to evolve and is directed toward improving cardiac pump function and/or reducing sudden arrhythmic death.

Left Ventricular Decompression During Speed Optimization Ramps in Patients Supported by Continuous-Flow Left Ventricular Assist Devices: Device-Specific Performance Characteristics and Impact on Diagnostic Algorithms.

BACKGROUND: Echocardiographic ramp tests have been widely used to help guide speed adjustments and for identification of potential device malfunctions in patients with axial continuous-flow left ventricular assist devices (LVADs) (Heartmate II LVAD [HMII]). Recently, the use of centrifugal-flow LVADs (Heartware LVAD [HVAD]) has been on the rise. The purpose of this study was to evaluate the utility of ramp tests for assessing ventricular decompression in HVAD patients. METHODS AND RESULTS: In this prospective study, ramp tests were performed before index hospitalization discharge or at the time of device malfunction. Vital signs, device parameters (including flow), and echocardiographic parameters (including left ventricular end-diastolic dimension [LVEDD], frequency of aortic valve [AV] opening, and valvular insufficiency) were recorded in increments of 100 rpm, from 2,300 rpm to 3,200 rpm. Twenty-six ramp tests were performed, 19 for speed optimization and 7 for device malfunction assessment. The average speed after the speed optimization ramp tests was 2,534.74 ± 156.32 RPM, and the AV closed at a mean speed of 2,751.77 ± 227.16 rpm, with 1 patient's valve remaining open at the maximum speed. The reduction in LVEDD for each speed increase was significantly different when the AV was open or closed, at -0.09 cm/increment and -0.15 cm/increment, respectively (P = .013), which is significantly different than previously established HMII LVEDD slopes. There were also significant changes in overall device flow (P = .001), upper flow (P = .031), and lower flow (P = .003) after AV closure. The power slope did not change significantly after the AV closed (P = .656). Five of the 19 tests were stopped before completion owing to suction events, but all tests reached ≥3,000 rpm. CONCLUSIONS: The parameter slopes for the HMII cannot be directly applied to ramp studies in HVAD patients. Overall, the LVEDD slope is drastically smaller in magnitude than the previously reported HMII findings, and speed adjustments were not based on the degree of left ventricular unloading. Therefore, the slope of the LVEDD-rpm relationship is not likely to be helpful in evaluating HVAD function.

Hemodynamic classifications of acute heart failure and their clinical application: ­ an update ­.

Acute heart failure (AHF) is classically defined by signs and symptoms related to elevated ventricular filling pressures. Regardless of precipitant, underlying etiology or ejection fraction, the vast majority of hospital admissions are the result of worsening chronic HF. For the acutely decompensated patient, 4 hemodynamic profiles, stratified by degree of congestion ("dry" or "wet") and adequacy of perfusion ("warm" or "cold") predict prognosis and guide therapy. Relief of congestion is the primary goal of AHF management. Loop diuretics remain the mainstay of AHF treatment, but new modalities such as veno-venous ultrafiltration are promising. For patients with evidence of hypoperfusion, vasoactive agents may be needed to facilitate diuresis. The decision to use vasodilators or inotropes is complex and the need for invasive hemodynamic monitoring is often determined by the individual patient's characteristics. Routine use of inotropes should be discouraged; however when used, the short-term hemodynamic benefits conferred by these agents must be balanced against their tendency to increase adverse events. Although these strategies are effective in alleviating symptoms in most patients, management dilemmas arise from cardiorenal interactions and limitations in effective novel therapies. Epidemiological studies continue to emphasize that AHF portends a poor prognosis. Further studies are needed to improve our understanding and outcomes in this growing patient population.

Hemodynamic and Clinical Performance of Hearts Donated After Circulatory Death.

BACKGROUND: Donor organ demand continues to outpace supply in heart transplantation. Utilization of donation after circulatory death (DCD) hearts could significantly increase heart donor availability for patients with advanced heart failure. OBJECTIVES: The purpose of this study was to describe hemodynamic and clinical profiles of DCD hearts in comparison to standard of care (SOC) hearts donated after brain death (DBD). METHODS: This single-center retrospective cohort study of consecutive heart transplant recipients analyzed right heart catheterization measurements, inotrope scores, echocardiograms, and clinical outcomes between DCD and DBD heart recipients. RESULTS: Between April 2016 and February 2022, 47 DCD and 166 SOC hearts were transplanted. Median time from DCD consent to transplant was significantly shorter compared with SOC waiting list time (17 days [6-28 days] vs 70 days [23-240 days]; P < 0.001). Right heart function was significantly impaired in DCD recipients compared with SOC recipients 1 week post-transplant (higher median right atrial pressure (10 mm Hg [8-13 mm Hg] vs 7 mm Hg [5-11 mm Hg]; P < 0.001), higher right atrial pressure to pulmonary capillary wedge pressure ratio (0.64 [0.54-0.82] vs 0.57 [0.43-0.73]; P = 0.016), and lower pulmonary arterial pulsatility index (1.66 [1.27-2.50] vs 2.52 [1.63-3.82]; P < 0.001), but was similar between groups by 3 weeks post-transplant. DCD and SOC recipient mortality was similar at 30 days (DCD 0 vs SOC 2%; P = 0.29) and 1 year post-transplant (DCD 3% vs SOC 8%; P = 0.16). CONCLUSIONS: DCD heart utilization is associated with transient post-transplant right heart dysfunction and short-term clinical outcomes otherwise similar to transplantation using DBD hearts.

Beyond the stethoscope: managing ambulatory heart failure during the COVID-19 pandemic.

There have been nearly 70 million cases of COVID-19 worldwide, with over 1.5 million deaths at the time of this publication. This global pandemic has mandated dramatic changes in healthcare delivery with a particular focus on social distancing in order to reduce viral transmission. Heart failure patients are among the highest utilizers of health care and are at increased risk for COVID-related vulnerabilities. Effectively managing this complex and resource-intensive patient population from a distance presents new and unique challenges. Here, we review relevant data on telemedicine and remote monitoring strategies for heart failure patients and provide a framework to help providers treat this population during the COVID-19 pandemic. This includes (i) dedicated pre-visit contact and planning (i.e. confirm clinical appropriateness, presence of compatible technology, and patient comfort); (ii) utilization of virtual clinic visits (use of telehealth platforms, a video-assisted exam, self-reported vital signs, and weights); and (iii) use of existing remote heart failure monitoring sensors when applicable (CardioMEMS, Optivol, and HeartLogic). While telemedicine and remote monitoring strategies are not new, these technologies are emerging as an important tool for the effective management of heart failure patients during the COVID-19 pandemic. In general, these strategies appear to be safe; however, additional data will be needed to determine their effectiveness with respect to both process and outcomes measures.

Management of Heart Failure and Cardiogenic Shock in Pregnancy.

PURPOSE OF REVIEW: While the prognosis of peripartum cardiomyopathy (PPCM) is generally more favorable than other cardiomyopathies, PPCM can be associated with cardiogenic shock and significant maternal morbidity in young women. The management of a pregnant woman in cardiogenic shock necessitates consideration of harm to the fetus. This review focuses on the management of these women. RECENT FINDINGS: A number of advances have increased the repertoire of therapies available to manage PPCM. Increased understanding of PPCM pathophysiology has led to a number of new and experimental medications. In the current era, mechanical circulatory support has been gaining a stronger presence in critical care and can be used in cardiogenic shock of the pregnant patient refractory to medical therapy. We discuss medical therapies, mechanical circulatory support, arrhythmia management, and a delivery plan in the setting of cardiogenic shock secondary to PPCM.

Mechanical circulatory support as a bridge to cardiac retransplantation: a single center experience.

BACKGROUND: Cardiac retransplantation is increasing in frequency. Recent data have shown that retransplantation outcomes are now comparable with primary transplantation. The use of mechanical circulatory support (MCS) as a bridge to retransplantation has similar post-retransplant outcomes to those without MCS, but the success of bridging patients to retransplant with MCS has not been well studied. METHODS: From January 2000 to February 2014 at Columbia University Medical Center, 84 patients were listed for retransplantation. Of this cohort, 48 patients underwent retransplantation, 15 were bridged with MCS, 24 died, and 6 clinically improved. A retrospective analysis was performed examining waiting list time, survival to retransplantation, and survival after retransplant. The effect of the United Network of Organ Sharing (UNOS) allocation policy change in 2006 on waiting list time and MCS use was also investigated. RESULTS: Of 48 patients who underwent retransplantation, 11 were bridged with MCS. Overall 1-year survival to retransplantation was 81.3%. There was no significant difference in waiting list survival (p = 0.71) in those with and without MCS. Death from cardiac arrest or multiorgan failure with infection was more frequent in the medically managed group (p = 0.002). After the UNOS 2006 allocation policy change, waiting list time (599 ± 936 days in Era 1 vs 526 ± 498 days in Era 2, p = 0.65) and waiting list survival (p = 0.22) between eras were comparable, but there was a trend toward greater use of MCS (p = 0.13). Survival after retransplant was acceptable. CONCLUSION: The use of MCS as a bridge to cardiac retransplantation is a reasonable strategy.

Early post-operative ventricular arrhythmias in patients with continuous-flow left ventricular assist devices.

BACKGROUND: Ventricular arrhythmias (VAs) are common in patients with a continuous-flow left ventricular assist device (CF-LVAD). The causes and clinical significance of early post-operative VAs have not previously been characterized in these patients. The purpose of this study was to assess the incidence, precipitants, and clinical impact of early VAs in patients supported by CF-LVADs. METHODS: Patients with a long-term CF-LVAD receiving care between January 1, 2012, and March 1, 2014, were enrolled and followed prospectively. Implantable cardioverter-defibrillators (ICDs) were interrogated at baseline and throughout the follow-up period. VA was defined as ventricular tachycardia or ventricular fibrillation lasting >30 seconds or effectively terminated by appropriate ICD tachytherapy or external defibrillation. The primary end-point was the occurrence of early VAs (within 30 days of surgery). Secondary end-points were right ventricular (RV) failure and need for VA ablation. RESULTS: There were 162 patients enrolled, and 38 (23.5%) experienced at least 1 early VA. Predictors of early VA were a history of pre-operative VAs, non-ischemic cardiomyopathy, and older age. Several conditions frequently encountered in the early post-operative period were identified as possible precipitants for VA episodes. Early VAs were associated with post-operative RV failure, particularly when patients received shocks instead of anti-tachycardia pacing. CONCLUSIONS: Early VAs are common and are associated with RV failure. ICD shocks, but not anti-tachycardia pacing, for early VAs are associated with acute worsening of RV failure.

Clinical Features and outcomes in adults with cardiogenic shock supported by extracorporeal membrane oxygenation.

Extracorporeal membrane oxygenation (ECMO) is an increasingly used supportive measure for patients with refractory cardiogenic shock (CS). Despite its increasing use, there remain minimal data regarding which patients with refractory CS are most likely to benefit from ECMO. We retrospectively studied all patients (n = 123) who underwent initiation of ECMO for CS from February 2009 to September 2014 at a single center. Baseline patient characteristics, including demographics, co-morbid illness, cause of CS, available laboratory values, and patient outcomes were analyzed. Overall, 69 patients (56%) were weaned from ECMO, with 48 patients (39%) surviving to discharge. Survivors were younger (50 vs 60 years; p ≤0.0001), had a lower rate of previous smoking (27 vs 56%; p = 0.01) and chronic kidney disease (2% vs 13%; p = 0.03), and had lower lactate measured soon after ECMO initiation (3.1 vs 10.2 mmol/l; p = 0.01). Patients with pulmonary embolism (odds ratio 8.0, 95% confidence interval 2.00 to 31.99; p = 0.01) and acute cardiomyopathy (odds ratio 7.5, 95% confidence interval 1.69 to 33.27; p = 0.01) had a higher rate of survival than acute myocardial infarction, chronic cardiomyopathy, and miscellaneous etiologies compared to postcardiotomy CS as a referent. In conclusion, survival after ECMO initiation differs based on underlying cause of CS. Survival may be lower in older patients and those with early evidence of persistent hypoperfusion after initiation of ECMO for CS.

Lipid-sugar particles for intracranial drug delivery: safety and biocompatibility.

Controlled release of drugs to specific locales in the brain has engendered considerable interest. Here we evaluate the safety and biocompatibility of 6-microm diameter particles composed of dipalmitoylphosphatidylcholine and chondroitin sulfate A, when delivered into the cerebral parenchyma and ventricles, and in the case of intravascular injection. Some particles were loaded with fluorescein-labeled albumin to facilitate detection. Particles placed in medium with cultured murine primary cortical neurons did not increase cell death at concentrations as high as 4 mg/ml. When particles (100 microg in 2 microl) were placed stereotactically in the striatum and lateral ventricles, there was no histological evidence on hematoxylin-eosin stained sections of tissue injury outside of the needle track in any animal 3, 7, and 14 days after injection (n=6 each), and no inflammation. Ventricular size was not significantly different between animals given intraventricular injections of particles and albumin solution at those time points (n=4 each). Intracarotid injection of particles at concentrations of 0.2 and 1 mg/ml (n=4 each) did not affect relative cerebral blood flow, and there were no embolic events on histology. In one animal in the group injected with 5 mg/ml (n=3), there was a profound decrease in rCBF, with patchy emboli on histology. These novel biodegradable particles are biocompatible in and around the brain, and may be safe for intracranial sustained drug delivery either in the parenchyma or into the CSF.

S1P3 receptors mediate the potent constriction of cerebral arteries by sphingosine-1-phosphate.

We characterized the effect of Sphingosine-1-phosphate (S1P) on vascular tone. S1P selectively constricted isolated cerebral, but not peripheral arteries, despite ubiquitous expression of S1P(1), S1P(2), S1P(3) and S1P(5) receptor mRNA. Clostridium B and C3 toxins and the rho-kinase inhibitor Y27632 (trans-N-(4-pyridyl)-4-(l-aminoethyl)-cyclohexane carboxamide) reduced this vasoconstriction to S1P, indicating that the response was mediated through Rho. Pertussis toxin displayed only weak inhibition, suggesting minor involvement of G(i/o) protein. The S1P effect was specifically reduced by adenovirus bearing a s1p(3) but not s1p(2), antisense construct. Furthermore, suramin, which selectively blocks S1P(3) receptors, inhibited the vasoconstrictor effect of S1P, indicating that S1P(3) receptors account for at least part of S1P-mediated vasoconstriction in cerebral arteries. In vivo, intracarotid injection of S1P decreased cerebral blood flow, an effect prevented by suramin treatment. Because S1P constricts cerebral blood vessels and is released from platelets during clotting, the S1P/S1P(3) system constitutes a novel potential target for cerebrovascular disease therapy.

Pre-operative mortality risk assessment in patients with continuous-flow left ventricular assist devices: application of the HeartMate II risk score.

BACKGROUND: Survival with left ventricular assist device (LVAD) therapy is dependent on appropriate patient selection. The HeartMate II risk score (HMRS) was recently derived and validated to predict 90-day mortality in clinical trial patients with continuous-flow LVADs. The aim of this study was to test HMRS validity in predicting survival at our institution. METHODS: We performed a retrospective analysis of patients implanted with HeartMate II (HMII; Thoratec, Pleasanton, CA) LVADs from March 31, 2004 to September 20, 2012 at the Columbia University Medical Center (CUMC). Patients were stratified according to HMRS profiles (HMRS Low < 1.58, 1.58 ≤ HMRS Medium ≤ 2.48, HMRS High > 2.48) calculated using age, albumin, creatinine, international normalized ratio (INR) and center volume. Outcome was defined as survival at 90 days after device implantation. RESULTS: HeartMate II LVADs were implanted in 205 patients. Pre-operative data from 201 patients were categorized into HMRS Low (n = 101; 1.04 [0.64 to 1.31]), HMRS Medium (n = 73; 1.98 [1.78 to 2.25]) and HMRS High (n = 27, 3.07 [2.70 to 3.43]) (p < 0.0001). Kaplan-Meier survival estimates at 90 days (HMRS Low 91.0 ± 2.9%, HMRS Medium 91.7 ± 3.2%, HMRS High 88.7 ± 6.1%) and at 1 year (HMRS Low 85.5 ± 3.8%, HMRS Medium 79.3 ± 5.5%, HMRS High 82.4 ± 8.4%) after LVAD implantation were not statistically different (p = 0.43). Prediction of 90-day mortality by receiver operating characteristic was poor (AUC = 0.56). CONCLUSION: HMRS stratification poorly discriminates 90-day mortality after HMII LVAD implantation at our institution. Its generalizability as a universal prognostic score may be limited.