Lavanya Bellumkonda

Continuous-flow devices and percutaneous site infections: Clinical outcomes

BACKGROUND Although continuous-flow left ventricular assist device (LVAD) support has become standard therapy, the complexities of device and patient management remain a challenge. In particular, percutaneous site infections (PSI) are a serious complication during the post-implant course. We sought to study the incidence, risk factors, and clinical effect of PSI. METHODS Data were obtained from the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) Registry. All adult patients who received a primary intracorporeal continuous flow LVAD between June 2006 and September 2010 were included. Descriptive statistics, Kaplan-Meier depictions, and multivariable analysis in the parametric hazard domain were used for statistical analysis. RESULTS A total of 239 PSIs were documented in 197 of 2,006 recipients (9.8%) of a continuous-flow LVAD. Mean follow-up was 8.1 months. Mean time to development of a PSI was 6.6 months. At 1 year after implant, nearly 19% of continuous-flow LVAD recipients developed a PSI. Multivariate analysis showed younger age (hazard ratio, 1.20; p < 0.0001) was the only factor predicting a PSI. Continuous-flow LVAD recipients who did not develop a PSI had improved survival (p = 0.004). Twenty-three patients died after development of a PSI. Sepsis was the most common cause of death (26.1%). CONCLUSIONS PSIs occur in approximately 19% of continuous-flow LVAD recipients by 12 months after implant. Young age is the only predictor of PSI. Importantly, development of a PSI adversely affects survival. Efforts to enhance driveline integration and to develop future totally implantable systems are warranted.

Loop Diuretic Efficiency A Metric of Diuretic Responsiveness With Prognostic Importance in Acute Decompensated Heart Failure

Background— Rather than the absolute dose of diuretic or urine output, the primary signal of interest when evaluating diuretic responsiveness is the efficiency with which the kidneys can produce urine after a given dose of diuretic. As a result, we hypothesized that a metric of diuretic efficiency (DE) would capture distinct prognostic information beyond that of raw fluid output or diuretic dose. Methods and Results— We independently analyzed 2 cohorts: (1) consecutive admissions at the University of Pennsylvania (Penn) with a primary discharge diagnosis of heart failure (n=657) and (2) patients in the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) data set (n=390). DE was estimated as the net fluid output produced per 40 mg of furosemide equivalents, then dichotomized into high versus low DE based on the median value. There was only a moderate correlation between DE and both intravenous diuretic dose and net fluid output (r2⩽0.26 for all comparisons), indicating that DE was describing unique information. With the exception of metrics of renal function and preadmission diuretic therapy, traditional baseline characteristics, including right heart catheterization variables, were not consistently associated with DE. Low DE was associated with worsened survival even after adjusting for in-hospital diuretic dose, fluid output, in addition to baseline characteristics (Penn: hazards ratio [HR], 1.36; 95% confidence interval [CI], 1.04−1.78; P=0.02; ESCAPE: HR, 2.86; 95% CI, 1.53−5.36; P=0.001). Conclusions— Although in need of validation in less-selected populations, low DE during decongestive therapy portends poorer long-term outcomes above and beyond traditional prognostic factors in patients hospitalized with decompensated heart failure.Background— Rather than the absolute dose of diuretic or urine output, the primary signal of interest when evaluating diuretic responsiveness is the efficiency with which the kidneys can produce urine after a given dose of diuretic. As a result, we hypothesized that a metric of diuretic efficiency (DE) would capture distinct prognostic information beyond that of raw fluid output or diuretic dose. Methods and Results— We independently analyzed 2 cohorts: (1) consecutive admissions at the University of Pennsylvania (Penn) with a primary discharge diagnosis of heart failure (n=657) and (2) patients in the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) data set (n=390). DE was estimated as the net fluid output produced per 40 mg of furosemide equivalents, then dichotomized into high versus low DE based on the median value. There was only a moderate correlation between DE and both intravenous diuretic dose and net fluid output (r2≤0.26 for all comparisons), indicating that DE was describing unique information. With the exception of metrics of renal function and preadmission diuretic therapy, traditional baseline characteristics, including right heart catheterization variables, were not consistently associated with DE. Low DE was associated with worsened survival even after adjusting for in-hospital diuretic dose, fluid output, in addition to baseline characteristics (Penn: hazards ratio [HR], 1.36; 95% confidence interval [CI], 1.04−1.78; P =0.02; ESCAPE: HR, 2.86; 95% CI, 1.53−5.36; P =0.001). Conclusions— Although in need of validation in less-selected populations, low DE during decongestive therapy portends poorer long-term outcomes above and beyond traditional prognostic factors in patients hospitalized with decompensated heart failure.

Hypochloraemia is strongly and independently associated with mortality in patients with chronic heart failure.

Hyponatraemia is strongly associated with adverse outcomes in heart failure. However, accumulating evidence suggests that chloride may play an important role in renal salt sensing and regulation of neurohormonal and sodium‐conserving pathways. Our objective was to determine the prognostic importance of hypochloraemia in patients with heart failure.

Substantial Discrepancy Between Fluid and Weight Loss During Acute Decompensated Heart Failure Treatment.

BACKGROUND Net fluid and weight loss are used ubiquitously to monitor diuretic response in acute decompensated heart failure research and patient care. However, the performance of these metrics has never been evaluated critically. The weight and volume of aqueous fluids such as urine should be correlated nearly perfectly and with very good agreement. As a result, significant discrepancy between fluid and weight loss during the treatment of acute decompensated heart failure would indicate measurement error in 1 or both of the parameters. METHODS The correlation and agreement (Bland-Altman method) between diuretic-induced fluid and weight loss were examined in 3 acute decompensated heart failure trials and cohorts: (1) Diuretic Optimization Strategies Evaluation (DOSE) (n = 254); (2) Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) (n = 348); and (3) Penn (n = 486). RESULTS The correlation between fluid and weight loss was modest (DOSE r = 0.55; ESCAPE r = 0.48; Penn r = 0.51; P < .001 for all), and the 95% limits of agreement were wide (DOSE -7.9 to 6.4 kg-L; ESCAPE -11.6 to 7.5 kg-L; Penn -14.5 to 11.3 kg-L). The median relative disagreement ranged from ±47.0% to 63.5%. A bias toward greater fluid than weight loss was found across populations (-0.74 to -2.1 kg-L, P ≤ .002). A consistent pattern of baseline characteristics or in-hospital treatment parameters that could identify patients at risk of discordant fluid and weight loss was not found. CONCLUSIONS Considerable discrepancy between fluid balance and weight loss is common in patients treated for acute decompensated heart failure. Awareness of the limitations inherent to these commonly used metrics and efforts to develop more reliable measures of diuresis are critical for both patient care and research in acute decompensated heart failure.

Rapid and Highly Accurate Prediction of Poor Loop Diuretic Natriuretic Response in Patients With Heart Failure

Background—Removal of excess sodium and fluid is a primary therapeutic objective in acute decompensated heart failure and commonly monitored with fluid balance and weight loss. However, these parameters are frequently inaccurate or not collected and require a delay of several hours after diuretic administration before they are available. Accessible tools for rapid and accurate prediction of diuretic response are needed. Methods and Results—Based on well-established renal physiological principles, an equation was derived to predict net sodium output using a spot urine sample obtained 1 or 2 hours after loop diuretic administration. This equation was then prospectively validated in 50 acute decompensated heart failure patients using meticulously obtained timed 6-hour urine collections to quantify loop diuretic-induced cumulative sodium output. Poor natriuretic response was defined as a cumulative sodium output of <50 mmol, a threshold that would result in a positive sodium balance with twice-daily diuretic dosing. Following a median dose of 3 mg (2–4 mg) of intravenous bumetanide, 40% of the population had a poor natriuretic response. The correlation between measured and predicted sodium output was excellent (r=0.91; P<0.0001). Poor natriuretic response could be accurately predicted with the sodium prediction equation (area under the curve =0.95, 95% confidence interval 0.89–1.0; P<0.0001). Clinically recorded net fluid output had a weaker correlation (r=0.66; P<0.001) and lesser ability to predict poor natriuretic response (area under the curve =0.76, 95% confidence interval 0.63–0.89; P=0.002). Conclusions—In patients being treated for acute decompensated heart failure, poor natriuretic response can be predicted soon after diuretic administration with excellent accuracy using a spot urine sample.

Left ventricular assist device pump thrombosis: is there a role for glycoprotein IIb/IIIa inhibitors?

Left ventricular assist devices (LVADs) fill a critical need by providing circulatory support to patients with end-stage heart failure who are either ineligible for heart transplant or too ill to stably wait for an eventual donor organ. Furthermore, they are critical to the arsenal of the heart failure cardiologist, given the supply/demand mismatch for donor organs. Unfortunately, these devices present their own complications. Despite antiplatelet agents and systemic anticoagulation, a number of patients present with pump thrombosis, a life-threatening event requiring either pump exchange or treatment with systemic thrombolytics. In an effort to avoid these morbid therapies, glycogen IIb/IIIa inhibitors, which have both antiplatelet and thrombolytic properties, have been proposed to treat pump thrombosis. We report here the largest case series using these agents and document a previously unreported high failure rate with this therapy.

Renal tubular resistance is the primary driver for loop diuretic resistance in acute heart failure

Loop diuretic resistance is a common barrier to effective decongestion in acute heart failure (AHF), and is associated with poor outcome. Specific mechanisms underlying diuretic resistance are currently unknown in contemporary AHF patients. We therefore aimed to determine the relative importance of defects in diuretic delivery vs. renal tubular response in determining diuretic response (DR) in AHF.

Pathophysiology of heart failure and frailty: a common inflammatory origin?

Frailty, a clinical syndrome that typically occurs in older adults, implies a reduced ability to tolerate biological stressors. Frailty accompanies many age‐related diseases but can also occur without overt evidence of end‐organ disease. The condition is associated with circulating inflammatory cytokines and sarcopenia, features that are shared with heart failure (HF). However, the biological underpinnings of frailty remain unclear and the interaction with HF is complex. Here, we describe the inflammatory pathophysiology that is associated with frailty and speculate that the inflammation that occurs with frailty shares common origins with HF. We discuss the limitations in investigating the pathophysiology of frailty due to few relevant experimental models. Leveraging current therapies for advanced HF and current known therapies to address frailty in humans may enable translational studies to better understand the inflammatory interactions between frailty and HF.

Right atrial pressure/pulmonary artery wedge pressure ratio: A more specific predictor of survival in pulmonary arterial hypertension

BACKGROUND Pulmonary arterial hypertension (PAH) is a progressive, fatal disease. Current prognostic models are not ideal, and identifying more accurate prognostic variables is needed. The objective of this study was to evaluate the relative prognostic value of the right atrial pressure/pulmonary artery wedge pressure (RAP/PAWP) ratio in PAH patients. We hypothesized that the RAP/PAWP ratio is more predictive of survival than any of the other measured or calculated hemodynamic variables. METHODS We performed a secondary analysis of a PAH cohort (Cohort 1) and validated our results in a separate cohort (Cohort 2). Cohort 1 included primarily patients enrolled in prospective, short-term, randomized clinical trials and subsequently followed long term. Cohort 2 included patients prospectively enrolled in a PAH registry at a tertiary PAH referral center. RESULTS Cohort 1 (n = 847) and Cohort 2 (n = 697) had a mean age of 47 and 54 years, respectively. Most were female (78% and 73%, respectively), Caucasian (83% and 82%), with advanced functional class disease status (New York Heart Association Functional Class III/IV 85% and 68%) and with significantly elevated hemodynamics (mean RAP/PAWP ratio: 1.2 and 1.0; pulmonary vascular resistance: 13.5 and 9.4 Wood units). RAP/PAWP ratio indicated a 1-year hazard ratio of 1.44 (p = 0.0001) and 1.35, respectively (p < 0.0001), and was the most consistently predictive hemodynamic variable across the 2 cohorts. These results remain valid even when adjusted for other covariables in multivariable regression models. CONCLUSIONS The RAP/PAWP ratio is a more specific predictor of survival than any other hemodynamic variable, and we recommend that it be used in clinical prognostication and PAH predictive models.

Influence of Titration of Neurohormonal Antagonists and Blood Pressure Reduction on Renal Function and Decongestion in Decompensated Heart Failure

Background—Reduction in systolic blood pressure (SBP reduction) during the treatment of acute decompensated heart failure is strongly and independently associated with worsening renal function. Our objective was to determine whether SBP reduction or titration of oral neurohormonal antagonists during acute decompensated heart failure treatment negatively influences diuresis and decongestion. Methods and Results—SBP reduction was evaluated from admission to discharge in consecutive acute decompensated heart failure admissions (n=656). Diuresis and decongestion were examined across a range of parameters, such as diuretic efficiency, fluid output, hemoconcentration, and diuretic dose. The average reduction in SBP was 14.4±19.4 mm Hg, and 77.6% of the population had discharge SBP lower than admission. SBP reduction was strongly associated with worsening renal function (odds ratio, 1.9; 95% confidence interval, 1.2–2.9; P=0.004), a finding that persisted after adjusting for parameters of diuresis and decongestion (odds ratio, 2.0; 95% confidence interval, 1.3–3.2; P=0.002). However, SBP reduction did not negatively affect diuresis or decongestion (P≥0.25 for all parameters). Uptitration of neurohormonal antagonists occurred in >50% of admissions and was associated with a modest additional reduction in blood pressure (⩽5.6 mm Hg). Notably, worsening renal function was not increased, and diuretic efficiency was significantly improved with the uptitration of neurohormonal antagonists. Conclusions—Despite a higher rate of worsening renal function, blood pressure reduction was not associated with worsening of diuresis or decongestion. Furthermore, titration of oral neurohormonal antagonists was actually associated with improved diuresis in this cohort. These results provide reassurance that the guideline-recommended titration of chronic oral medication during acute decompensated heart failure hospitalization may not be antagonistic to the short-term goal of decongestion.