Susan M. Joseph

Isosorbide mononitrate in heart failure with preserved ejection fraction

BACKGROUND Nitrates are commonly prescribed to enhance activity tolerance in patients with heart failure and a preserved ejection fraction. We compared the effect of isosorbide mononitrate or placebo on daily activity in such patients. METHODS In this multicenter, double-blind, crossover study, 110 patients with heart failure and a preserved ejection fraction were randomly assigned to a 6-week dose-escalation regimen of isosorbide mononitrate (from 30 mg to 60 mg to 120 mg once daily) or placebo, with subsequent crossover to the other group for 6 weeks. The primary end point was the daily activity level, quantified as the average daily accelerometer units during the 120-mg phase, as assessed by patient-worn accelerometers. Secondary end points included hours of activity per day during the 120-mg phase, daily accelerometer units during all three dose regimens, quality-of-life scores, 6-minute walk distance, and levels of N-terminal pro-brain natriuretic peptide (NT-proBNP). RESULTS In the group receiving the 120-mg dose of isosorbide mononitrate, as compared with the placebo group, there was a nonsignificant trend toward lower daily activity (-381 accelerometer units; 95% confidence interval [CI], -780 to 17; P=0.06) and a significant decrease in hours of activity per day (-0.30 hours; 95% CI, -0.55 to -0.05; P=0.02). During all dose regimens, activity in the isosorbide mononitrate group was lower than that in the placebo group (-439 accelerometer units; 95% CI, -792 to -86; P=0.02). Activity levels decreased progressively and significantly with increased doses of isosorbide mononitrate (but not placebo). There were no significant between-group differences in the 6-minute walk distance, quality-of-life scores, or NT-proBNP levels. CONCLUSIONS Patients with heart failure and a preserved ejection fraction who received isosorbide mononitrate were less active and did not have better quality of life or submaximal exercise capacity than did patients who received placebo. (Funded by the National Heart, Lung, and Blood Institute; ClinicalTrials.gov number, NCT02053493.).

Cardiovascular phenotype in HFpEF patients with or without diabetes: a RELAX trial ancillary study.

Background RELAX was a multicenter randomized trial of sildenafil versus placebo in heart failure and preserved ejection fraction (HFpEF) with rigorous entry criteria and extensive phenotypic characterization of participants.

EVALUATION OF GI BLEEDING AFTER IMPLANTATION OF LEFT VENTRICULAR ASSIST DEVICE

BACKGROUND Left ventricular assist devices (LVADs) have revolutionized the management of end-stage heart failure (ESHF). However, unexpectedly high rates of GI bleeding (GIB) have been described, and etiology and outcome remain unclear. OBJECTIVE To determine the prevalence, etiology, and outcome of GIB in LVAD recipients. DESIGN Retrospective case series. SETTING Tertiary care academic university hospital. PATIENTS 154 ESHF patients (55.4 years, 122 men/32 women) with LVADs implanted over a 10-year period. MAIN OUTCOME MEASUREMENTS Overt or occult GIB prompting endoscopic evaluation ≥ 7 days after LVAD implantation. RESULTS Over a mean of 0.9 ± 0.1 years of follow-up, 29 patients (19%) experienced 44 GIB episodes. Patients with GIB were older and received anticoagulation therapy before devices were implanted (P ≤ .02 for each). GIB was overt (n = 31) rather than occult (n = 13), and most patients presented with melena (n = 22, 50%); hemodynamic instability was observed in 13.6%. Each bleeding episode required 2.1 ± 0.1 diagnostic or therapeutic procedures, and a source was localized in 71%. Upper endoscopy provided the highest diagnostic yield; peptic bleeding (n = 14) and vascular malformations (n = 8) dominated the findings. Endoscopy was safe and well tolerated. Overall mortality was 35%, none directly from GIB. LIMITATION Retrospective design. CONCLUSIONS Rates of GIB with LVADs are higher than that seen in other patient populations, including those receiving anticoagulation and antiplatelet therapy. GIB episodes are mostly overt and predominantly from the upper GI tract. Endoscopy is safe in the LVAD population.

Hemolysis in left ventricular assist device: A retrospective analysis of outcomes

BACKGROUND Hemolysis is becoming increasingly recognized as a major complication of left ventricular assist device (LVAD) support. Data regarding risk factors, prevalence, and outcomes are limited. To better define the characteristics and prognosis of hemolysis, we present a retrospective case-control study of LVAD patients in our institution. METHODS A detailed record review was conducted of 18 patients supported with the HeartMate II (HMII; Thoratec Corp, Pleasanton, CA) who were diagnosed with hemolysis, and their data were compared with 82 patients who received an LVAD implant during the same period who did not develop hemolysis. Patients were excluded if they did not survive hospitalization at the time of LVAD implantation. The primary end points of this analysis were time to death and time to first hospitalization. RESULTS Of 100 total patients, 18 HMII patients (18%) were diagnosed with hemolysis. Those with hemolysis were younger, had significantly higher lactate dehydrogenase and bilirubin levels, lower international normalized ratio, and no difference in cannula velocities by transthoracic echocardiography. Patient survival in the hemolysis group was markedly decreased at 1 year (38.9% vs 89.3%, p < 0.001), but no differences in hospitalization (p = 0.57) were observed. Partial to complete thrombosis was noted in all of the pumps at explant. CONCLUSIONS These findings demonstrate that hemolysis is associated with high mortality, likely serving as a marker of pump thrombosis. Elevated lactate dehydrogenase and bilirubin levels are important indicators for hemolysis, and lower international normalized ratio may pre-dispose for this worrisome condition. Diagnosis should prompt clinicians to consider pump exchange or explant, listing for transplantation, or intensifying anti-coagulation.

The use of eptifibatide for suspected pump thrombus or thrombosis in patients with left ventricular assist devices

BACKGROUND Pump thrombosis in patients with left ventricular assist devices (LVADs) continues to present treatment challenges. Anti-coagulation strategies used to treat this complication are empiric and without firm data for guidance. The addition of a platelet glycoprotein IIb/IIIa inhibitor to intravenous anti-coagulation has been suggested by several case series and recent guidelines. The aim of this study was to evaluate our use of eptifibatide for the treatment of suspected pump thrombus/thrombosis. METHODS This retrospective, single-center cohort study was performed at Barnes-Jewish Hospital. The medical informatics system was queried to identify all LVAD patients who received eptifibatide for suspected pump thrombus/thrombosis from January 1, 2011, through April 30, 2013. RESULTS A total of 17 patients (16 HeartMate II [Thoratec, Pleasanton, CA], 1 HeartWare [HeartWare International Inc, Framingham, MA]) with 22 separate administration attempts received eptifibatide (dose range, 0.1-2 μg/kg/min) for suspected pump thrombus/thrombosis presenting as one or more of the following findings: elevated lactate dehydrogenase, decreased haptoglobin, elevated plasma free hemoglobin, LVAD dysfunction, or new, persistently high LVAD power. The mean time from device implantation to eptifibatide therapy was 47.34 days (range, 3.88-397.67 days). Of the 22 attempts, 5 (22.7%) resulted in resolution of 1 or more patient-specific indicators of LVAD thrombus/thrombosis. Three patients (17.6%) had resolution of an indicator while also remaining free from continued hemolysis, death, pump exchange, or emergent heart transplant. Bleeding events were common, with 11 patients (64.7%) experiencing bleeding during the infusion. Seven patients (41.2%) died, with intraparenchymal hemorrhage as the cause of death in 2 patients. Pump exchange was performed in 3 patients. CONCLUSIONS Our limited experience indicates the risk of using eptifibatide outweighs the proposed benefit of salvaging the existing LVAD in the setting of suspected pump thrombus/thrombosis at our institution.

Comparable Performance of the Kansas City Cardiomyopathy Questionnaire in Patients With Heart Failure With Preserved and Reduced Ejection Fraction

Background—Despite the growing epidemic of heart failure with preserved ejection fraction (HFpEF), no valid measure of patients’ health status (symptoms, function, and quality of life) exists. We evaluated the Kansas City Cardiomyopathy Questionnaire (KCCQ), a validated measure of HF with reduced EF, in patients with HFpEF. Methods and Results—Using a prospective HF registry, we dichotomized patients into HF with reduced EF (EF⩽ 40) and HFpEF (EF≥50). The associations between New York Heart Association class, a commonly used criterion standard, and KCCQ Overall Summary and Total Symptom domains were evaluated using Spearman correlations and 2-way ANOVA with differences between patients with HF with reduced EF and HFpEF tested with interaction terms. Predictive validity of the KCCQ Overall Summary scores was assessed with Kaplan–Meier curves for death and all-cause hospitalization. Covariate adjustment was made using Cox proportional hazards models. Internal reliability was assessed with Cronbach’s &agr;. Among 849 patients, 200 (24%) had HFpEF. KCCQ summary scores were strongly associated with New York Heart Association class in both patients with HFpEF (r=−0.62; P<0.001) and HF with reduced EF (r=−0.55; P=0.27 for interaction). One-year event-free rates by KCCQ category among patients with HFpEF were 0 to 25=13.8%, 26 to 50=59.1%, 51 to 75=73.8%, and 76 to 100=77.8% (log rank P<0.001), with no significant interaction by EF (P=0.37). The KCCQ domains demonstrated high internal consistency among patients with HFpEF (Cronbach’s &agr;=0.96 for overall summary and ≥0.69 in all subdomains). Conclusions—Among patients with HFpEF, the KCCQ seems to be a valid and reliable measure of health status and offers excellent prognostic ability. Future studies should extend and replicate our findings, including the establishment of its responsiveness to clinical change.

The incidence, risk factors, and outcomes associated with late right-sided heart failure in patients supported with an axial-flow left ventricular assist device

BACKGROUND Early right-sided heart failure (RHF) after left ventricular assist device (LVAD) implantation is associated with increased mortality, but little is known about patients who develop late RHF (LRHF). We evaluated the incidence, risk factors, and clinical impact of LRHF in patients supported by axial-flow LVADs. METHODS Data were analyzed from 537 patients enrolled in the HeartMate II (HM II; Thoratec/St. Jude) destination therapy clinical trial. LRHF was defined as the development of clinical RHF accompanied by the need for inotropic support occurring more than 30 days after discharge from the index LVAD implant hospitalization. Clinical variables, quality of life, rehospitalizations, and survival were compared between patients with and without LRHF. RESULTS LRHF developed in 41 patients (8%), with a median time to LRHF of 480 days. A higher preoperative blood urea nitrogen and increased central venous pressure-to-pulmonary capillary wedge pressure ratio were independent predictors of LRHF. The Michigan and HMII RHF risk scores were both associated with an increased likelihood of LRHF (p < 0.05). Patients with LRHF had worse quality of life according to the Kansas City Cardiomyopathy Questionnaire (61 ± 26 vs 70 ± 21; p < 0.05), poorer functional capacity by 6-minute walk distance (275 ± 189 m vs 312 ± 216 m; p < 0.05), and more rehospitalizations (6 vs 3; p < 0.001). LRHF was associated with decreased survival (p < 0.001). CONCLUSIONS LRHF is an important complication in patients with LVADs and is associated with worse quality of life, reduced functional capacity, more frequent hospitalizations, and worse survival compared with those without LRHF.

Intra-Aortic Balloon Counterpulsation in Patients With Chronic Heart Failure and Cardiogenic Shock: Clinical Response and Predictors of Stabilization

OBJECTIVE The aim of this work was to characterize the clinical response and identify predictors of clinical stabilization after intra-aortic balloon counterpulsation (IABP) support in patients with chronic systolic heart failure in cardiogenic shock before implantation of a left ventricular assist device (LVAD). BACKGROUND Limited data exist regarding the clinical response to IABP in patients with chronic heart failure in cardiogenic shock. METHODS We identified 54 patients supported with IABP before LVAD implantation. Criteria for clinical decompensation after IABP insertion and before LVAD included the need for more advanced temporary support, initiation of mechanical ventilation or dialysis, increase in vasopressors/inotropes, refractory ventricular arrhythmias, or worsening acidosis. The absence of these indicated stabilization. RESULTS Clinical decompensation after IABP occurred in 23 patients (43%). Both patients who decompensated and those who stabilized had similar hemodynamic improvements after IABP support, but patients who decompensated required more vasopressors/inotropes. Clinical decompensation after IABP was associated with worse outcomes after LVAD implantation, including a 3-fold longer intensive care unit stay and 5-fold longer time on mechanical ventilation (P < .01 for both). Although baseline characteristics were similar between groups, right and left ventricular cardiac power indexes (cardiac power index = cardiac index × mean arterial pressure/451) identified patients who were likely to stabilize (area under the receiver operating characteristic curve = 0.82). CONCLUSIONS Among patients with chronic systolic heart failure who develop cardiogenic shock, more than one-half of patients stabilized with IABP support as a bridge to LVAD. Baseline measures of right and left ventricular cardiac power, reflecting work performed for a given flow and pressure, may allow clinicians to identify patients with sufficient contractile reserve who will be likely to stabilize with an IABP versus those who may need more aggressive ventricular support.

Left atrial decompression pump for severe heart failure with preserved ejection fraction: theoretical and clinical considerations.

OBJECTIVES The purpose of this study was to provide insight into the potential for left atrium (LA) to aortic mechanical circulatory support as a treatment for patients with heart failure with preserved ejection fraction (HFpEF). BACKGROUND Although HFpEF arises from different etiologies, 1 hallmark of all forms of this syndrome is a small or minimally-dilated left ventricle (LV). Consequently, the use of traditional mechanical circulatory support in end-stage patients has been difficult. In contrast, HFpEF is also characterized by a large LA. METHODS Hemodynamic characteristics of 4 distinct HFpEF phenotypes were characterized from the published data: 1) hypertrophic cardiomyopathies; 2) infiltrative diseases; 3) nonhypertrophic HFpEF; and 4) HFpEF with common cardiovascular comorbidities (e.g., hypertension). Employing a previously-described cardiovascular simulation, the effects of a low-flow, micropump-based LA decompression device were modeled. The effect of sourcing blood from the LV versus the LA was compared. RESULTS For all HFpEF phenotypes, mechanical circulatory support significantly increased cardiac output, provided a mild increase in blood pressure, and markedly reduced pulmonary and LA pressures. LV sourcing of blood reduced LV end-systolic volume into a range likely to induce suction. With LA sourcing, however, LV end-systolic volume increased compared with baseline. Due to pre-existing LA enlargement, LA volumes remained sufficiently elevated, thus minimizing the risk of suction. CONCLUSIONS This theoretical analysis suggests that a strategy involving pumping blood from the LA to the arterial system may provide a viable option for end-stage HFpEF. Special considerations apply to each of the 4 types of HFpEF phenotypes described. Finally, an HFpEF-specific clinical profile scoring system (such as that of INTERMACS [Interagency Registry for Mechanically Assisted Circulatory Support]) would aid in the selection of patients with the appropriate risk-benefit ratio for implantation of an active pump.

Comparable Performance of the Kansas City Cardiomyopathy Questionnaire in Patients With Heart Failure With Preserved and Reduced Ejection FractionClinical Perspective

Background—Despite the growing epidemic of heart failure with preserved ejection fraction (HFpEF), no valid measure of patients’ health status (symptoms, function, and quality of life) exists. We evaluated the Kansas City Cardiomyopathy Questionnaire (KCCQ), a validated measure of HF with reduced EF, in patients with HFpEF. Methods and Results—Using a prospective HF registry, we dichotomized patients into HF with reduced EF (EF⩽ 40) and HFpEF (EF≥50). The associations between New York Heart Association class, a commonly used criterion standard, and KCCQ Overall Summary and Total Symptom domains were evaluated using Spearman correlations and 2-way ANOVA with differences between patients with HF with reduced EF and HFpEF tested with interaction terms. Predictive validity of the KCCQ Overall Summary scores was assessed with Kaplan–Meier curves for death and all-cause hospitalization. Covariate adjustment was made using Cox proportional hazards models. Internal reliability was assessed with Cronbach’s &agr;. Among 849 patients, 200 (24%) had HFpEF. KCCQ summary scores were strongly associated with New York Heart Association class in both patients with HFpEF (r=−0.62; P<0.001) and HF with reduced EF (r=−0.55; P=0.27 for interaction). One-year event-free rates by KCCQ category among patients with HFpEF were 0 to 25=13.8%, 26 to 50=59.1%, 51 to 75=73.8%, and 76 to 100=77.8% (log rank P<0.001), with no significant interaction by EF (P=0.37). The KCCQ domains demonstrated high internal consistency among patients with HFpEF (Cronbach’s &agr;=0.96 for overall summary and ≥0.69 in all subdomains). Conclusions—Among patients with HFpEF, the KCCQ seems to be a valid and reliable measure of health status and offers excellent prognostic ability. Future studies should extend and replicate our findings, including the establishment of its responsiveness to clinical change.