Laith Alshawabkeh

Thermodilution vs Estimated Fick Cardiac Output Measurement in Clinical Practice: An Analysis of Mortality From the Veterans Affairs Clinical Assessment, Reporting, and Tracking (VA CART) Program and Vanderbilt University

Importance Thermodilution (Td) and estimated oxygen uptake Fick (eFick) methods are widely used to measure cardiac output (CO). They are often used interchangeably to make critical clinical decisions, yet few studies have compared these approaches as applied in medical practice. Objectives To assess agreement between Td and eFick CO and to compare how well these methods predict mortality. Design, Setting, and Participants This investigation was a retrospective cohort study with up to 1 year of follow-up. The study used data from the Veterans Affairs Clinical Assessment, Reporting, and Tracking (VA CART) program. The findings were corroborated in a cohort of patients cared for at Vanderbilt University, an academic referral center. Participants were more than 15 000 adults who underwent right heart catheterization, including 12 232 in the Veterans Affairs cohort between October 1, 2007, and September 30, 2013, and 3391 in the Vanderbilt cohort between January 1, 1998, and December 31, 2014. Exposures A single cardiac catheterization was performed on each patient with CO estimated by both Td and eFick methods. Cardiac output was indexed to body surface area (cardiac index [CI]) for all analyses. Main Outcomes and Measures All-cause mortality over 90 days and 1 year after catheterization. Results Among 12 232 VA patients (mean [SD] age, 66.4 [9.9] years; 3.3% female) who underwent right heart catheterization in this cohort study, Td and eFick CI estimates correlated modestly (r = 0.65). There was minimal mean difference (eFick minus Td = −0.02 L/min/m2, or −0.4%) but wide 95% limits of agreement between methods (−1.3 to 1.3 L/min/m2, or −50.1% to 49.4%). Estimates differed by greater than 20% for 38.1% of patients. Low Td CI (<2.2 L/min/m2 compared with normal CI of 2.2-4.0 L/min/m2) more strongly predicted mortality than low eFick CI at 90 days (Td hazard ratio [HR], 1.71; 95% CI, 1.47-1.99; &khgr;2 = 49.5 vs eFick HR, 1.42; 95% CI, 1.22-1.64; &khgr;2 = 20.7) and 1 year (Td HR, 1.53; 95% CI, 1.39-1.69; &khgr;2 = 71.5 vs eFick HR, 1.35; 1.22-1.49; &khgr;2 = 35.2). Patients with a normal CI by both methods had 12.3% 1-year mortality. There was no significant additional risk for patients with a normal Td CI but a low eFick CI (12.9%, P = .51), whereas a low Td CI but normal eFick CI was associated with higher mortality (15.4%, P = .001). The results from the Vanderbilt cohort were similar in the context of a more balanced sex distribution (46.6% female). Conclusions and Relevance There is only modest agreement between Td and eFick CI estimates. Thermodilution CI better predicts mortality and should be favored over eFick in clinical practice.

Burden of Heart Failure in Adults with Congenital Heart Disease

Patients born with congenital heart disease (CHD) have benefited from remarkable advances in surgical and catheter-based interventions. As a result, the majority of children born with even the most complex forms of CHD live into adulthood. The specialized field of adult CHD (ACHD) was born out of the necessity to care for this new population of survivors of childhood CHD and their distinctive features. In this review, relevant aspects of ACHD that lead to, and are affected by, heart failure will be examined along with the increasing prevalence of HF in the burgeoning population of ACHD. We also highlight the challenges in defining HF in this particular group of patients.

Clinical pharmacology relevant to older adults with cardiovascular disease

Although older adults are generally among the highest users of cardiovascular medications, they are typically underrepresented or excluded from most efficacy and safety trials. Drug developers are usually reluctant to include many senior adults in randomized controlled clinical trials in part due to their high prevalence of multiple comorbidities, frailty, and polypharmacy; and to age-related pharmacokinetic and pharmacodynamic complexities. Consequently, there is often insufficient high quality evidence-based data to inform pharmacologic management of common cardiovascular conditions on older adults. In the absence of data, clinicians often rely on conceptual principles regarding metabolism and drug-drug interactions to minimize adverse drug events, but this is often not well-substantiated or standardized. A related challenge is poor cardiovascular medication adherence among older adults, and its detrimental impact on their health outcomes. In this brief review we highlight some aspects of these topics.

Association of Albuminuria With Major Adverse Outcomes in Adults With Congenital Heart Disease: Results From the Boston Adult Congenital Heart Biobank

Importance Albuminuria is associated with adverse outcomes in diverse groups of patients, but the importance of albuminuria in the emerging population of increasingly complex adults with congenital heart disease (ACHD) remains unknown. Objective To assess the prevalence, risk factors, and prognostic implications of albuminuria in ACHD. Design, Setting, and Participants This prospective study assessed a cohort of ambulatory patients aged 18 years and older who were examined at an ACHD referral center and enrolled in the Boston ACHD Biobank between May 17, 2012, to August 5, 2016. Albuminuria was defined as an urine albumin-to-creatinine (ACR) ratio of 30 mg/g or more. Main Outcomes and Measures Death or nonelective cardiovascular hospitalization, defined as overnight admission for heart failure, arrhythmia, thromboembolic events, cerebral hemorrhage, and/or disease-specific events. Results We measured the ACR of 612 adult patients with CHD (mean [SD] age, 38.6 [13.4] years; 308 [50.3%] women). Albuminuria was present in 106 people (17.3%) and was associated with older age (patients with ACR <30 mg/g: mean [SD]: 37.5 [13.2] years; vs patients with ACR ≥30 mg/g: 43.8 [13.1] years; P < .001), presence of diabetes mellitus (ACR <30 mg/g: 13 of 506 [2.6%]; vs ≥30 mg/g: 11 of 106 [10.4%]; P < .001), lower estimated glomerular filtration rate (ACR <30 mg/g: median [interquartile range (IQR)]: 103.3 [90.0-116.4] mL/min/1.73 m2; ACR ≥30 mg/g: 99.1 [78.8-108.7] mL/min/1.73 m2; P = .002), and cyanosis (ACR <30 mg/g: 23 of 506 [5.1%]; vs ACR ≥30 mg/g: 21 of 106 [22.6%]; P < .001). After a mean (SD) follow-up time of 270 (288) days, 17 patients (2.5%) died, while 68 (11.1%) either died or experienced overnight inpatient admission. Albuminuria predicted outcome, with 30 of 106 patients with albuminuria (28.3%) affected vs 38 of 506 patients without albuminuria (7.5%; hazard ratio [HR], 3.0; 95% CI, 1.9-4.9; P < .001). Albuminuria was also associated with increased mortality (11 of 106 [10.4%]; vs 6 of 506 [1.2%] in patients with and without albuminuria, respectively; HR, 6.4; 95% CI, 2.4-17.3; P < .001). Albuminuria was associated with the outcomes only in patients with a biventricular circulation (HR, 4.5; 95% CI, 2.5-8.0) and not those with single-ventricle circulation (HR, 1.0; 95% CI, 0.4-2.8; P = 0.01 compared with biventricular circulation group). Among 133 patients (21.7%) in NYHA functional class 2, albuminuria was strongly associated with death or nonelective hospitalization. Conclusions and Relevance Albuminuria is common and is associated with increased risk for adverse outcome in patients with ACHD with biventricular circulation. Albuminuria appears especially useful in stratifying risk in patients categorized as NYHA functional class 2.

Prospective cohort study of C-reactive protein as a predictor of clinical events in adults with congenital heart disease: results of the Boston adult congenital heart disease biobank

Aims Despite the well-defined association of high-sensitivity hsCRP with cardiovascular outcomes in apparently healthy adults and those with acquired heart disease, the relevance of this inflammatory marker in adults with congenital heart disease (ACHD) remains unclear. We aimed to examine the clinical correlates and prognostic value of high-sensitivity C-reactive protein levels in ACHD. Methods and results We conducted a prospective cohort study of (n = 707) outpatient ACHD (age 39 ± 14 years, 49% women), enrolled mainly at a referral centre, who had serum hsCRP measured in conjunction with a clinical assessment between 2012 and 2016. We analysed clinical correlates of hsCRP and its association with adverse events including the primary combined outcome of all-cause mortality or non-elective cardiovascular hospitalization. Higher hsCRP was strongly associated with measures of functional status including New York Heart Association class and peak V̇O2, and with comorbidities such as atrial arrhythmia. During average follow-up of 815 ± 536 days, 114 patients (16%) experienced the primary outcome, including 29 deaths. Having elevated hsCRP, in the highest (≥2.98 mg/L) compared with the lower three quartiles, conferred increased risk for the primary outcome [30.5% vs. 11.3%, adjusted hazard ratio (HR) = 2.00, 95% confidence interval (CI) 1.35-2.97; P = 0.0006] and all-cause mortality (11.9% vs. 1.5%, adjusted HR = 4.23, 95% CI 1.87-9.59; P = 0.0006). Elevated hsCRP was associated with adverse outcomes across ACHD subgroups and other patient characteristics. Conclusion Adults with congenital heart disease with elevated hsCRP have not only worse functional status and exercise capacity, but also greater risk for death or non-elective cardiovascular hospitalization. Further study is warranted to characterize the role of inflammation in the pathophysiology of ACHD.

Current Role of Blood and Urine Biomarkers in the Clinical Care of Adults with Congenital Heart Disease

Purpose of ReviewThere is an increasing number of adult patients with congenital heart disease (CHD). While several biomarkers have been validated and integrated into general cardiology clinical practice, these tests are often applied to adults with CHD in the absence of disease-specific validation. Although these patients are often grouped into a single population, there is heterogeneous pathophysiology, variable disease chronicity, extensive multisystem involvement, and a low event rate relative to acquired heart disease. These stand as challenges to systematic investigation and clinical application of biomarkers for adults with CHD. This paper reviews recent studies investigating the use of biomarkers in this population, with emphasis on biomarkers applied in clinical adult CHD care.Recent FindingsA handful of biomarkers have been integrated into adult CHD practice, such as iron studies in cyanotic heart disease and stool alpha-1 antitrypsin for diagnosis of protein losing enteropathy in the Fontan circulation. Use of kidney and liver tests has been studied in prognostication of adult CHD patients. A few other biomarkers like natriuretic peptides and troponins seem likely to provide useful information in other ACHD situations based on limited disease-specific data and extrapolation from acquired heart disease.SummaryMore research is needed to support the robust validity of most existing clinical biomarkers in adult congenital cardiology practice. Until data from larger, prospectively enrolled cohorts are available, clinical use of biomarkers in these patients will require careful interpretation with attention to underlying pathophysiology, as well as detailed understanding of potential pitfalls of specific assays and clinical contexts.

Years of Able Life in Older Persons—The Role of Cardiovascular Imaging and Biomarkers: The Cardiovascular Health Study

Background As the U.S. population grows older, there is greater need to examine physical independence. Previous studies have assessed risk factors in relation to either disability or mortality, but an outcome that combines both is still needed. Methods and Results The Cardiovascular Health Study is a population‐based, prospective study where participants underwent baseline echocardiogram, measurement of carotid intima‐media thickness (IMT), and various biomarkers, then followed for up to 18 years. Years of able life (YAL) constituted the number of years the participant was able to perform all activities of daily living. Linear regression was used to model the relationship between selected measures and outcomes, adjusted for confounding variables. Among 4902 participants, mean age was 72.6±5.4 years, median YAL for males was 8.8 (interquartile range [IQR], 4.3 to 13.8) and 10.3 (IQR, 5.8 to 15.8) for females. Reductions in YAL in the fully adjusted model for females and males, respectively, were: −1.34 (95% confidence interval [CI], −2.18, −0.49) and −1.41 (95% CI, −2.03, −0.8) for abnormal left ventricular (LV) ejection fraction, −0.5 (95% CI, −0.78, −0.22) and −0.62 (95% CI, −0.87, −0.36) per SD increase in LV mass, −0.5 (95% CI, −0.7, −0.29) and −0.79 (95% CI, −0.99, −0.58) for IMT, −0.5 (95% CI, −0.64, −0.37) and −0.79 (95% CI, −0.94, −0.65) for N‐terminal pro‐brain natriuretic peptide, −1.08 (95% CI, −1.34, −0.83) and −0.73 (95% CI, −0.97, −0.5) for high‐sensitivity troponin‐T, and −0.26 (95% CI, −0.42, −0.09) and −0.23 (95% CI, −0.41, −0.05) for procollagen‐III N‐terminal propeptide. Most tested variables remained significant even after adjusting for incident cardiovascular (CV) disease. Conclusions In this population‐based cohort, variables obtained by CV imaging and biomarkers of inflammation, coagulation, atherosclerosis, myocardial injury and stress, and cardiac collagen turnover were associated with YAL, an important outcome that integrates physical ability and longevity in older persons.

OUTCOMES OF A PREOPERATIVE “BRIDGING” STRATEGY WITH GLYCOPROTEIN IIB/IIIA INHIBITORS FOR PREVENTING PERIOPERATIVE STENT THROMBOSIS IN PATIENTS WITH DRUG-ELUTING STENTS WHO UNDERGO SURGERY NECESSITATING INTERRUPTION OF THIENOPYRIDINE ADMINISTRATION

Results: Mean age was 65±1.2 years and all patients were men. Surgery occurred after a mean time of 13.9±1.7 and 8.7±2 months post stenting for noncardiac and cardiac surgery respectively. A glycoprotein IIb/IIIa inhibitor was administered preoperatively for a mean of 7.1±0.4 and 7.8±0.7 days, respectively then discontinued 4 hours before surgery. The majority of patients continued to receive aspirin through the perioperative period (33 patients for NCS group and 15 patients for cardiac surgery group). Clopidogrel was restarted as early as possible in the postoperative period. Among patients undergoing noncardiac surgery, two patients (3.9%, 95% conidence intervals 0.5%, 13.5%) had acute stent thrombosis in the immediate postoperative period and four patients had major bleeding by the GUSTO criteria. One of the cardiac surgery patients had probable stent thrombosis one hour post surgery.

Contemporary ACHD training and the reality of the field in the United States

BACKGROUND Care delivery for the growing population of adults living with congenital heart disease (CHD) has been met with challenges due to a shortage of physicians trained to care for this population. To meet this urgent need, restructuring and standardization of the training programs were implemented in 2015. The consequences of such a system on the graduating fellows have not been examined. METHODS A 25-question electronic survey was distributed to early career physicians who graduated following training in adult CHD (ACHD) care between 2015 and 2017 and are currently practicing in the United States. The survey results were anonymous. RESULTS Of the 30 physicians who trained in ACHD between 2015 and 2017 in the U.S., 21 (70%) responded to the survey. The majority completed a 2-year ACHD program, practice at an adult hospital, are happy with their current job, spend most of their time in ACHD-related activities, make on average around 250,000 USD for entry level positions, and prioritize supportive leadership and colleagues. Their training was adequate for their job requirements. However, the acquisition of an additional skill, in addition to clinical ACHD care, allowed them to secure a more ideal job. A sizeable number of jobs required program building or expansion with only 9.5% of trainees comfortable doing so immediately after graduation. CONCLUSIONS The new ACHD training curriculum successfully meets most of the needs for ACHD jobs. Integration of specialty tracks, ensuring uniformity in the quality of training between programs, and promoting leadership skills may improve career prospects.

Relationship of Red Cell Distribution Width to Adverse Outcomes in Adults With Congenital Heart Disease (from the Boston Adult Congenital Heart Biobank)

Red cell distribution width (RDW), a measure of variability in red cell size, predicts adverse outcomes in acquired causes of heart failure. We examined the relation of RDW and outcomes in adults with congenital heart disease. We performed a prospective cohort study on 696 ambulatory patients ≥18years old enrolled in the Boston Adult Congenital Heart Disease Biobank between 2012 and 2016 (mean age 38.7 ± 13.5 years; 49.9% women). The combined outcome was all-cause mortality or nonelective cardiovascular hospitalization. Most patients had moderately or severely complex congenital heart disease (42.5% and 38.5%, respectively). Mean RDW was 14.0 ± 1.3%. RDW >15% was present in 81 patients (11.6%). After median 767days of follow-up, 115 patients sustained the primary combined outcome, including 31 who died. Higher RDW predicted both the combined outcome (hazard ratio [HR] for RDW >15% = 4.5, 95% confidence interval [CI] 3.0 to 6.6; HR per + 1SD RDW = 1.8, 95% CI 1.6 to 2.0, both p <0.0001) and death alone (HR for RDW >15% = 7.1, 95% CI 3.5 to 14.4; HR per + 1SD RDW = 1.8, 95% CI 1.6 to 2.0, both p <0.0001). RDW remained an independent predictor of the combined outcome after adjusting for age, cyanosis, congenital heart disease complexity, ventricular systolic function, New York Heart Association functional class, hemoglobin concentration, mean corpuscular volume, high-sensitivity C-reactive protein and estimated glomerular filtration rate (HR per + 1SD RDW = 1.5, 95% CI 1.2 to 1.9, p <0.0001). RDW also remained an independent predictor of mortality alone after adjustment for age plus each variable individually. In conclusion, elevated RDW is an independent predictor of all-cause mortality or nonelective cardiovascular hospitalization in adults with congenital heart disease. This simple clinical biomarker identifies increased risk for adverse events even among patients with preserved functional status.