Standardization of the Right Heart Catheterization and the Emerging Role of Advanced Hemodynamics in Heart Failure.

The accurate assessment of hemodynamics is paramount to providing timely and efficacious care for patients presenting in cardiogenic shock. Recently, the regular use of the pulmonary artery catheter in cardiogenic shock has had a resurgence with emerging data indicating improved survival in the modern era. Optimal multidisciplinary management of advanced heart failure and cardiogenic shock relies on our ability to effectively communicate and understand the complete hemodynamic assessment. Standardization of data acquisition and a renewed focus on the physiological processes, and thresholds driving disease progression, including the coupling ratio and myocardial reserve, are needed to fully understand and interpret the hemodynamic assessment. This State-of-the-Art review discusses best practices in the cardiac catheterization laboratory as well as emerging data on the prognostic role of emerging advanced hemodynamic parameters.

Postoperative tolvaptan use in left ventricular assist device patients: The TOLVAD randomized pilot study.

PURPOSE: Tolvaptan, a selective vasopressin type-2 antagonist, has been shown to increase serum sodium (Na) and urine output in hyponatremic left ventricular assist device (LVAD) patients in retrospective studies. In this prospective randomized pilot study, we aimed to assess the efficacy of tolvaptan in this population. METHODS: We conducted a prospective, randomized, non-blinded pilot study of LVAD recipients with post-operative hyponatremia (Na < 135 mEq/L) (NCT05408104). Eligible participants were randomized to receive tolvaptan 15 mg daily in addition to usual care versus usual care alone. The primary outcome was a change in Na level and estimated glomerular filtration rate (eGFR), from the first post-operative day of hyponatremia (the day of randomization) to discharge. RESULTS: A total of 33 participants were enrolled, and 28 underwent randomization (median age 55 [IQR 50-62]), 21% women, 54% Black, 32% ischemic cardiomyopathy, median baseline Na 135 (IQR 134-138). Fifteen participants were randomized to tolvaptan (TLV) and 13 were randomized to usual care alone (No-TLV). Mean change in Na from randomization to discharge in the TLV group was 2.7 mEq/L (95%CI 0.7-4.7, p = 0.013) and 1.8 (95%CI 0.5-4.0, p = 0.11) in the No-TLV group, though baseline and final Na levels were similar between groups. The mean change in eGFR was 2.6 ml/min/1.73 m2 (95%CI 10.1-15.3, p = 0.59) in TLV versus 7.5 ml/min/1.73 m2 (95%CI 5.2-20.2, p = 0.15) in No-TLV. TLV participants had significantly more urine output than No-TLV patients during their first 24 h after randomization (3294 vs 2155 ml, p = 0.043). CONCLUSION: TLV significantly increases urine output, with nominal improvement in Na level, in hyponatremic post-operative LVAD patients without adversely impacting renal function.

Biventricular Pacing Versus Right Ventricular Pacing in Patients Supported With LVAD.

OBJECTIVES: This study sought to evaluate the effects of right ventricular (RV) pacing versus biventricular (BiV) pacing on quality of life, functional status, and arrhythmias in LVAD patients. BACKGROUND: Cardiac resynchronization therapy (CRT) and left ventricular assist devices (LVADs) independently improve outcomes in heart failure patients, but the effects of combining these therapies remains unknown. We present the first prospective randomized study evaluating the effects of RV versus BiV pacing on quality of life, functional status, and arrhythmias in LVAD patients. METHODS: In this prospective randomized crossover study, LVAD patients with prior CRT devices were alternated on RV and BiV pacing for planned 7-14-day periods. Ambulatory step count, 6-minute walk test distance, Kansas City Cardiomyopathy Questionnaire scores, arrhythmia burden, CRT lead function, and echocardiographic data were collected with each pacing mode. RESULTS: Thirty patients were enrolled, with a median age of 65 years, 67% male, and mean duration of LVAD support of 309 days. Compared with BiV pacing, RV-only pacing resulted in 29% higher mean daily step count, 11% higher 6-minute walk test distance, and 7% improved KCCQ-12 score (all p < 0.03). LV end-diastolic volume was significantly lower with RV pacing (220 vs. 250 mL; p = 0.03). Fewer patients had ventricular tachyarrhythmia episodes during RV pacing (p = 0.03). RV lead impedance was lower with RV pacing (p = 0.047), but no significant differences were observed in impedance across other CRT leads. CONCLUSIONS: In the first prospective randomized study comparing variable pacing in LVAD patients, RV pacing was associated with significantly improved functional status, quality of life, fewer ventricular tachyarrhythmias, and stable lead impedance compared with BiV pacing. This study supports turning off LV lead pacing in LVAD patients with CRT.

Discordance between lactic acidemia and hemodynamics in patients with advanced heart failure.

BACKGROUND: Elevated lactic acid (LA) levels carry a poor prognosis in patients with shock. Data are lacking on the significance of LA levels in patients with acute decompensated heart failure (ADHF). HYPOTHESIS: This study assessed the relationship between LA levels, hemodynamics and clinical outcomes. METHODS: This was a retrospective analysis of registry data of 100 advanced heart failure patients presenting for right heart catheterization (RHC) for concern of ADHF. LA levels (normal ≤2.1 mmol/L) were obtained prior to RHC; no significant changes in therapy were made between LA collection and RHC. RESULTS: Median age was 58 (47.3, 64.8) years; 57% were receiving inotropes prior to RHC. Median pulmonary capillary wedge pressure (PCWP) and cardiac index (CI) were 28 (21, 35) mmHg and 2.0 (1.7, 2.5) L/min/m2 , respectively. Eighty patients had normal LA prior to RHC. There was no correlation between LA levels and PCWP (R = 0.09, p = .38); 63% of the normal LA group had a PCWP >24 mmHg. There was a moderate inverse correlation between LA and CI (R = - 0.40; p < .001); 58% of the normal LA group had a CI <2.2 L/min/m2 . Thirty-day survival free of death/hospice, inotrope dependence, progression to heart transplant/left-ventricular assist device implant was comparable between the normal and elevated LA groups (28% vs. 20%; p = .17). CONCLUSION: In patients presenting with ADHF, normal LA levels do not exclude the presence of depressed CI (a hemodynamic criteria for cardiogenic shock) and may not offer accurate risk stratification. Invasive hemodynamics should not be delayed based on normal LA levels alone.

Aortic pulsatility index predicts clinical outcomes in heart failure: a sub-analysis of the ESCAPE trial.

AIMS: Aortic pulsatility index (API), calculated as (systolic-diastolic blood pressure)/pulmonary capillary wedge pressure (PCWP), is a novel haemodynamic measurement representing both cardiac filling pressures and contractility. We hypothesized that API would better predict clinical outcomes than traditional haemodynamic metrics of cardiac function. METHODS AND RESULTS: The Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) trial individual-level data were used. Routine haemodynamic measurements, including Fick cardiac index (CI), and the advanced haemodynamic metrics of API, cardiac power output (CPO), and pulmonary artery pulsatility index (PAPI) were calculated after final haemodynamic-monitored optimization. The primary outcome was a composite endpoint of death or need for orthotopic heart transplant (OHT) or left ventricular assist device (LVAD) at 6 months. A total of 433 participants were enrolled in the ESCAPE trial of which 145 had final haemodynamic data. Final API measurements predicted the primary outcome, OR 0.47 (95% CI 0.32-0.70, P < 0.001), while CI, CPO, and PAPI did not. Receiver operator characteristic analyses of final advanced haemodynamic measurements indicated API best predicted the primary outcome with a cutoff of 2.9 (sensitivity 76.2%, specificity 55.3%, correctly classified 61.4%, area-under-the-curve 0.71), compared with CPO, CI, and PAPI. Kaplan-Meier analyses indicated API ≥ 2.9 was associated with greater freedom from the primary outcome (83.5%), compared with API < 2.9 (58.4%), P = 0.001. While PAPI was also significantly associated, CI and CPO were not. CONCLUSIONS: The novel haemodynamic measurement API better predicted clinical outcomes in the ESCAPE trial when compared with traditional invasive haemodynamic metrics of cardiac function.

High sensitivity Troponin-T for prediction of adverse events in patients with COVID-19.

BACKGROUND: High sensitivity cardiac troponin-T (hs-TnT) has been associated with mortality in patients hospitalized with COVID-19. We aimed to determine if hs-TnT levels and their timing are independent predictors of adverse events in these patients. DESIGN: Retrospective chart review was performed for all patients hospitalized at our institution between 23 March 2020 and 13 April 2020 who were found to be COVID-19-positive. Clinical, demographic, and laboratory variables including initial and peak hs-TnT were recorded. Univariable and multivariable analyses were completed for a primary composite endpoint of in-hospital death, intubation, need for critical care, or cardiac arrest. RESULTS: In the 276 patients analysed, initial hs-TnT above the median (≥17 ng/L) was associated with increased length of stay, need for vasoactive medications, and death, along with the composite endpoint (OR 3.92, p < 0.001). Multivariable analysis demonstrated that elevated initial hs-TnT was independently associated with the primary endpoint (OR 2.92, p = 0.01). Late-peaking hs-TnT (OR 2.19 for each additional day until peak, p < 0.001) was also independently associated with the composite endpoint. CONCLUSIONS: In patients hospitalized with COVID-19, hs-TnT identifies patients at high risk for adverse in-hospital events, and trends of hs-TnT over time, particularly during the first day, provide additional prognostic information.

Early experience of COVID-19 in 2 heart transplant recipients: Case reports and review of treatment options.

The coronavirus disease 2019 (COVID-19) pandemic poses special challenges to immunocompromised transplant patients. Given the paucity of proven data in treating COVID-19, management of these patients is difficult, rapidly evolving, and mainly based on anecdotal experience. We report 2 cases of heart transplant (HT) recipients with COVID-19. The first is a 59-year-old female with HT in 2012 who presented on March 20, 2020 with fever, hypoxia, and ground-glass opacities on chest X-ray. She quickly progressed to acute hypoxic respiratory failure and vasoplegic shock. Despite reduction in immunosuppression and treatment with tocilizumab, intravenous immunoglobulin, hydroxychloroquine, lopinavir/ritonavir, and broad-spectrum antibiotics, she ultimately died from multiorgan failure. The second case is a 75-year-old man with HT in 2000 who presented on April 2, 2020 after curbside testing revealed positive COVID-19. Given a milder presentation compared to the first patient, antimetabolite was discontinued and only hydroxychloroquine was started. Because of a lack of clinical improvement several days later, tocilizumab, methylprednisolone, and therapeutic anticoagulation were initiated. The patient clinically improved with decreasing oxygen requirements and was discharged home. These 2 cases highlight the wide range of different presentations of COVID-19 in HT recipients and the rapidity with which the management of these patients is evolving.

Metabolic Dysfunction in Continuous-Flow Left Ventricular Assist Devices Patients and Outcomes.

Background Metabolic impairment is common in heart failure patients. Continuous-flow left ventricular assist devices (CF-LVADs) improve hemodynamics and outcomes in patients with advanced heart failure; however, the effect of CF-LVADs on metabolic status is unknown. This study aims to evaluate the changes in metabolic status following CF-LVAD implantation and measure the correlation of metabolic status with outcomes. Methods and Results Prospective data on CF-LVAD patients were obtained. Metabolic evaluation, including hemoglobin A1C, free and total testosterone, thyroid-stimulating hormone (TSH), and free T4, was obtained before and at multiple time points following implantation. Patients with nonelevated thyroid-stimulating hormone and normal hemoglobin A1C and testosterone levels were defined as having normal metabolic status. Baseline characteristics, hemodynamics, and outcomes were collected. One hundred six patients were studied, of which 56 had paired data at baseline and 1- to 3-month follow-up. Before implantation, 75% of patients had insulin resistance, 86% of men and 39% of women had low free testosterone, and 44% of patients had abnormal thyroid function. There was a significant improvement in hemoglobin A1C, free testosterone, and thyroid-stimulating hormone following implantation (P<0.001 for all). Patients with normal hemoglobin A1C (<5.7%) following implantation had higher 1-year survival free of heart failure readmissions (78% versus 23%; P<0.001). Patients with normal metabolic status following implantation also had higher 1-year survival free of heart failure readmissions (92% versus 54%; P=0.04). Conclusions Metabolic dysfunction is highly prevalent in advanced heart failure patients and improves after CF-LVAD implantation. Normal metabolic status is associated with a significantly higher rate of 1-year survival free of heart failure readmissions.

Increase in short-term risk of rejection in heart transplant patients receiving granulocyte colony-stimulating factor.

BACKGROUND: Neutropenia is a significant adverse event after heart transplantation (HT) and increases infection risk. Granulocyte colony-stimulating factor (G-CSF) is commonly used in patients with neutropenia. In this work, we assessed the adverse effects of G-CSF treatment in the setting of a university hospital. METHODS: Data on HT patients from January 2008 to July 2016 were reviewed. Patients who received G-CSF were identified and compared with patients without a history of therapy. Baseline characteristics, rejection episodes, and outcomes were collected. Data were analyzed by incidence rates, time to rejection and survival were analyzed using Kaplan-Meier curves, and odds ratios were generated using logistic regression analysis. RESULTS: Two hundred twenty-two HT patients were studied and 40 (18%) received G-CSF for a total of 85 total neutropenic events (0.79 event/patient year). There were no differences in baseline characteristics between the groups. In the 3 months after G-CSF, the incidence rate of rejection was 0.067 event/month. In all other time periods considered free of G-CSF effect, the incidence rate was 0.011 event/month. This rate was similar to the overall incidence rate in the non-GCSF group, which was 0.010 event/month. There was a significant difference between the incidence rates in the G-CSF group at 0 to 3 months after G-CSF administration and the non-GCSF group (p = 0.04), but not for the other time periods (p = 0.5). Freedom from rejection in the 3 months after G-CSF administration was 87.5% compared with 97.5% in the non-GCSF group (p = 0.006). CONCLUSIONS: G-CSF administration was found to be associated with significant short-term risk of rejection. This suggests the need for increased surveillance during this time period.

New Challenges in the Treatment of Patients With Left Ventricular Support: LVAD Thrombosis.

Mechanical circulatory support has revolutionized the treatment of heart failure, affording patients significantly improved survival and quality of life. However, further advancements in this technology have been hindered by adverse events, particularly gastrointestinal bleeding, driveline infection, stroke, and device thrombosis. Recently, there has been a renewed focus on device thrombosis as the reported incidence has increased. This review focuses on an update on the diagnostic modalities and current treatment algorithms of this serious complication.

Interactions between smoking, pulmonary surfactant protein B, and atherosclerosis in the general population: the Dallas Heart Study.

OBJECTIVE: Pulmonary surfactant protein B (SP-B), an alveolar protein normally detectable at only very low concentrations in blood, circulates at higher levels among smokers and those with alveolar injury and inflammation. We hypothesized that SP-B may serve as a marker of the vascular effects of smoking and would thus be associated with subclinical measures of atherosclerosis. METHODS AND RESULTS: Plasma levels of SP-B were measured in 3294 subjects, ages 30 to 65, enrolled in the Dallas Heart Study, a probability-based population sample of Dallas County adults. Coronary artery calcium (CAC) was measured by computed tomography and abdominal aortic plaque (AP) by magnetic resonance imaging. The cohort comprised 29% current and 17% former smokers. The overall prevalence of CAC was 22%, and that of AP was 39%. Median SP-B levels were 5-fold higher among current versus never smokers (P<0.0001) and were significantly correlated with estimated pack-years smoked (Spearman ρ=0.35, P<0.0001). Increasing levels of SP-B also associated with other traditional cardiac risk factors and higher levels of inflammatory biomarkers. In univariable analyses, increasing SP-B quartiles associated with higher prevalence of both CAC and AP (P(trend)<0.0001 for each). In multivariable analyses adjusting for traditional cardiovascular risk factors, SP-B remained associated with AP (OR 1.87 for the 4th versus 1st quartiles, 95% confidence interval 1.39 to 2.51; P<0.0001) but not CAC. An interaction was observed between SP-B, smoking status, and AP (P(interaction)=0.01), such that SP-B associated with AP in current smokers (adjusted OR 2.15 for the 4th versus 1st quartile, 95% confidence interval 1.26 to 3.67; P=0.005) but not in former or never smokers. CONCLUSIONS: Circulating levels of SP-B increase with greater smoking burden and independently associate with abdominal AP among current smokers. Our findings support further investigation of the role of SP-B as a marker of the vascular effects of smoking.

Body art among minority high school athletes: prevalence, interest and satisfaction; parental knowledge and consent.

Of 997 minority high school students, 8.6% had tattoos and 8% piercings (excluding earlobes); 21% with tattoos and 59% with piercings would not repeat the experience. Fifty-eight percent with tattoos and 43% with piercings reported parental knowledge before the procedure; 75% and 80%, respectively, were asked for proof of parental consent.

Electrospray diagnostics by Fourier analysis of current oscillations and fast imaging.

The different spraying modes in electrospray ionization sources exhibit large variations in their ion yield and stability. To achieve consistently optimal ion production, active control of the spray parameters is desirable. To diagnose the changes in spraying mode, the spray current and its Fourier spectrum were monitored under a wide range of conditions, that is, as a function of the spray voltage, liquid flow rate, and composition. Most Fourier spectra indicated a strong dc component, a low-frequency branch at low flow rates and applied voltages, and a high-frequency branch and their harmonics. Changing of these parameters resulted in several spraying mode changes that were reflected in the Fourier spectra of the spray current. Significant mode changes and the malformation of the Taylor cone were detected as peak shifts or sudden changes in the spectrum quality. This was confirmed by fast imaging that showed a reduction in the size of the Taylor cone under hydrophobic tip conditions and rapid periodic ejection of filaments and droplets for high conductivity solutions. Comparing the oscillation frequencies of Taylor cones of different sizes, good correlation was found with the frequencies of capillary waves on comparablly sized liquid spheres. Spray stability was also linked with the positional stability of the contact line between the liquid meniscus and the capillary tip.

GntP is the Escherichia coli Fructuronic acid transporter and belongs to the UxuR regulon.

Escherichia coli has four gluconate transporters, GntP, GntU, GntT, and IdnT, which are members of the major facilitator superfamily. The physiological function of GntP was previously unknown and is the subject of this study. GntP is not induced by gluconate, and despite being located adjacent to genes involved in glucuronate catabolism, gntP does not encode a glucuronate transporter. Here we identify gntP as the gene which encodes the fructuronate transporter. We show that gntP is induced by fructuronate and is a new member of the UxuR regulon: gntP is derepressed in an uxuR strain, UxuR binds in vitro specifically to an operator site that overlaps the gntP promoter, and UxuR binding is eliminated by fructuronate. Transcription of gntP requires activation by cyclic AMP (cAMP)-cAMP receptor protein. A gntP mutant cannot grow on fructuronate but grows normally on glucuronate and gluconate. Thus, the UxuR regulon is a module of sugar acid catabolism whose physiological role is for growth on fructuronate. Glucuronate, because it proceeds through a fructuronate intermediate, must induce the UxuR regulon and must also induce the ExuR regulon, which encodes the glucuronate transporter, ExuT, and the first step in its catabolism, UxaC. Thus, hexuronate catabolism in E. coli requires both the ExuR and UxuR regulons, while fructuronate catabolism requires only the UxuR regulon.