Kimberly A. Parks

Use of amino-terminal pro-B-type natriuretic peptide to guide outpatient therapy of patients with chronic left ventricular systolic dysfunction.

OBJECTIVES The aim of this study was to evaluate whether chronic heart failure (HF) therapy guided by concentrations of amino-terminal pro-B-type natriuretic peptide (NT-proBNP) is superior to standard of care (SOC) management. BACKGROUND It is unclear whether standard HF treatment plus a goal of reducing NT-proBNP concentrations improves outcomes compared with standard management alone. METHODS In a prospective single-center trial, 151 subjects with HF due to left ventricular (LV) systolic dysfunction were randomized to receive either standard HF care plus a goal to reduce NT-proBNP concentrations ≤1,000 pg/ml or SOC management. The primary endpoint was total cardiovascular events between groups compared using generalized estimating equations. Secondary endpoints included effects of NT-proBNP-guided care on patient quality of life as well as cardiac structure and function, assessed with echocardiography. RESULTS Through a mean follow-up period of 10 ± 3 months, a significant reduction in the primary endpoint of total cardiovascular events was seen in the NT-proBNP arm compared with SOC (58 events vs. 100 events, p = 0.009; logistic odds for events 0.44, p = 0.02); Kaplan-Meier curves demonstrated significant differences in time to first event, favoring NT-proBNP-guided care (p = 0.03). No age interaction was found, with elderly patients benefitting similarly from NT-proBNP-guided care as younger subjects. Compared with SOC, NT-proBNP-guided patients had greater improvements in quality of life, demonstrated greater relative improvements in LV ejection fraction, and had more significant improvements in both LV end-systolic and -diastolic volume indexes. CONCLUSIONS In patients with HF due to LV systolic dysfunction, NT-proBNP-guided therapy was superior to SOC, with reduced event rates, improved quality of life, and favorable effects on cardiac remodeling. (Use of NT-proBNP Testing to Guide Heart Failure Therapy in the Outpatient Setting; NCT00351390).

Soluble Concentrations of the Interleukin Receptor Family Member ST2 and β-Blocker Therapy in Chronic Heart Failure

Background—Concentrations of soluble (s)ST2 predict prognosis in heart failure. We recently found changing doses of &bgr;-blocker (BB) may affect sST2 concentrations. It remains unclear whether sST2 concentrations identify benefit of BB therapy, however. Methods and Results—A total of 151 subjects with heart failure attributable to left ventricular systolic dysfunction were examined in this post hoc analysis; >96% were taking BB at enrollment. Medication regimen and sST2 values were obtained during 10 months. Cardiovascular events were examined as a function of baseline sST2 status (low ⩽35 versus high >35 ng/mL) and final achieved BB dose (high ≥50 versus low <50 mg daily equivalent dose of metoprolol succinate). Patients with low sST2 titrated to high-dose BB had the lowest cardiovascular event rate at 0.53 events (P=0.001), and lowest cumulative hazard (P=0.003). Those with low sST2/low-dose BB, or high sST2/high-dose BB had intermediate outcomes (0.92 and 1.19 events). Patients with high sST2 treated with low-dose BB had the highest cardiovascular event rate (2.08 events) and the highest cumulative hazard. Compared with low sST2/high-dose BB, those with high sST2 treated with low-dose BB had an odds ratio of 6.77 (P<0.001) for a cardiovascular event. Patients with low sST2/low-dose BB or high sST2/high-dose BB had intermediate odds ratios for cardiovascular events (P=0.18 and 0.02). Similar results were found for heart failure hospitalization and cardiovascular death. Conclusions—Although BB therapy exerted dose-related benefits across all study participants, sST2 measurement identifies patients with chronic heart failure who may particularly benefit from higher BB doses. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT00351390.

QRS morphology, left ventricular lead location, and clinical outcome in patients receiving cardiac resynchronization therapy.

AIMS Several studies have reported a poor outcome with cardiac resynchronization therapy (CRT) in non-left bundle branch block (LBBB) patients. Although the left ventricular (LV) lead location is an important determinant of the clinical outcome, there is scant information regarding its role in non-LBBB patients. This study sought to examine the impact of electrical and anatomical location of the LV lead in relation to baseline QRS morphology on the CRT outcome. METHODS AND RESULTS A left ventricular lead electrical delay (LVLED) was measured intra-procedurally as an interval between QRS onset on the surface electrocardiogram (ECG) to the peak of sensed electrogram on LV lead and corrected for QRS width. The impact of the LVLED on time to first heart failure hospitalization (HFH), and composite outcome of all-cause mortality, HFH, LVAD implantation, and cardiac transplantation at 3 years was assessed. Among 144 patients (age 67 ± 12 years, QRS duration 156 ± 28 ms, non-LBBB 43%), HFH was higher in non-LBBB compared with LBBB (43.5 vs. 24%, P = 0.015). Within LBBB, patients with the long LVLED (≥50%) had 17% HFH vs. 53% in the short LVLED (<50%), P = 0.002. Likewise in non-LBBB, patients with the long LVLED compared with the short LVLED had a lower HFH (36 vs. 61%, P = 0.026). In adjusted Cox proportional hazards model, the long LVLED in LBBB and non-LBBB was associated with an improved outcome. Specifically, in non-LBBB, LVLED ≥50% was associated with improved event-free survival with respect to time to first HFH (HR: 0.34; P = 0.011) and composite outcome (HR: 0.41; P = 0.019). CONCLUSION Cardiac resynchronization therapy delivered from an LV pacing site characterized by the long LVLED was associated with the favourable outcome in LBBB and non-LBBB patients.

Heart rescue: the role of mechanical circulatory support in the management of severe refractory cardiogenic shock.

Purpose of reviewCardiogenic shock is present in 3.5% of patients presenting with acute decompensated heart failure. Despite advances in therapy, mortality remains high, approaching 70% in some settings. Recent management strategies have incorporated the use of mechanical circulatory support (MCS), which has been associated with better survival in nonrandomized trials. MCS is increasingly used in the acute setting and has become an important treatment modality for cardiogenic shock. Recent findingsSmall studies have demonstrated improved survival when MCS is instituted early in the management of cardiogenic shock. Numerous case reports support the benefit of MCS for various causes of cardiogenic shock, including acute myocardial infarction, cardiac allograft rejection, myocarditis and refractory arrhythmias. SummaryThis article will review novel strategies in the management of cardiogenic shock including percutaneous MCS (intra-aortic balloon pump, Impella, TandemHeart, venoarterial extracorporeal membrane oxygenation) and surgically implanted devices (CentriMag) that are used for short-term management. We will review the mechanisms involved in cardiogenic shock and discuss management and device selection strategies.

Patient engagement with a mobile web-based telemonitoring system for heart failure self-management: a pilot study.

Background Intensive remote monitoring programs for congestive heart failure have been successful in reducing costly readmissions, but may not be appropriate for all patients. There is an opportunity to leverage the increasing accessibility of mobile technologies and consumer-facing digital devices to empower patients in monitoring their own health outside of the hospital setting. The iGetBetter system, a secure Web- and telephone-based heart failure remote monitoring program, which leverages mobile technology and portable digital devices, offers a creative solution at lower cost. Objective The objective of this pilot study was to evaluate the feasibility of using the iGetBetter system for disease self-management in patients with heart failure. Methods This was a single-arm prospective study in which 21 ambulatory, adult heart failure patients used the intervention for heart failure self-management over a 90-day study period. Patients were instructed to take their weight, blood pressure, and heart rate measurements each morning using a WS-30 bluetooth weight scale, a self-inflating blood pressure cuff (Withings LLC, Issy les Moulineaux, France), and an iPad Mini tablet computer (Apple Inc, Cupertino, CA, USA) equipped with cellular Internet connectivity to view their measurements on the Internet. Outcomes assessed included usability and satisfaction, engagement with the intervention, hospital resource utilization, and heart failure-related quality of life. Descriptive statistics were used to summarize data, and matched controls identified from the electronic medical record were used as comparison for evaluating hospitalizations. Results There were 20 participants (mean age 53 years) that completed the study. Almost all participants (19/20, 95%) reported feeling more connected to their health care team and more confident in performing care plan activities, and 18/20 (90%) felt better prepared to start discussions about their health with their doctor. Although heart failure-related quality of life improved from baseline, it was not statistically significant (P=.55). Over half of the participants had greater than 80% (72/90 days) weekly and overall engagement with the program, and 15% (3/20) used the interactive voice response telephone system exclusively for managing their care plan. Hospital utilization did not differ in the intervention group compared to the control group (planned hospitalizations P=.23, and unplanned hospitalizations P=.99). Intervention participants recorded shorter average length of hospital stay, but no significant differences were observed between intervention and control groups (P=.30). Conclusions This pilot study demonstrated the feasibility of a low-intensive remote monitoring program leveraging commonly used mobile and portable consumer devices in augmenting care for a fairly young population of ambulatory patients with heart failure. Further prospective studies with a larger sample size and within more diverse patient populations is necessary to determine the effect of mobile-based remote monitoring programs such as the iGetBetter system on clinical outcomes in heart failure.

Randomized, Controlled Trial of an Advance Care Planning Video Decision Support Tool for Patients With Advanced Heart Failure

Background: Conversations about goals of care and cardiopulmonary resuscitation (CPR)/intubation for patients with advanced heart failure can be difficult. This study examined the impact of a video decision support tool and patient checklist on advance care planning for patients with heart failure. Methods: This was a multisite, randomized, controlled trial of a video-assisted intervention and advance care planning checklist versus a verbal description in 246 patients ≥64 years of age with heart failure and an estimated likelihood of death of >50% within 2 years. Intervention participants received a verbal description for goals of care (life-prolonging care, limited care, and comfort care) and CPR/intubation plus a 6-minute video depicting the 3 levels of care, CPR/intubation, and an advance care planning checklist. Control subjects received only the verbal description. The primary analysis compared the proportion of patients preferring comfort care between study arms immediately after the intervention. Secondary outcomes were CPR/intubation preferences and knowledge (6-item test; range, 0–6) after intervention. Results: In the intervention group, 27 (22%) chose life-prolonging care, 31 (25%) chose limited care, 63 (51%) selected comfort care, and 2 (2%) were uncertain. In the control group, 50 (41%) chose life-prolonging care, 27 (22%) selected limited care, 37 (30%) chose comfort care, and 8 (7%) were uncertain (P<0.001). Intervention participants (compared with control subjects) were more likely to forgo CPR (68% versus 35%; P<0.001) and intubation (77% versus 48%; P<0.001) and had higher mean knowledge scores (4.1 versus 3.0; P<0.001). Conclusions: Patients with heart failure who viewed a video were more informed, more likely to select a focus on comfort, and less likely to desire CPR/intubation compared with patients receiving verbal information only. Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01589120.

Pre-Capillary Pulmonary Hypertension and Right Ventricular Dilation Predict Clinical Outcome in Cardiac Resynchronization Therapy

OBJECTIVES This study examined the prognostic significance of pre- and post-capillary components of pulmonary hypertension (PH) in patients receiving cardiac resynchronization therapy (CRT). BACKGROUND PH is common in patients with left ventricular systolic dysfunction (LVSD) receiving CRT. The impact of PH subtype on clinical outcome in CRT is unknown. METHODS The study population consisted of 101 patients (average age 66 ± 13 years, left ventricular ejection fraction 0.23 ± 0.07, and New York Heart Association functional class 3.2 ± 0.4) who underwent right heart catheterization in the 6 months before CRT. PH was defined as a mean pulmonary artery pressure ≥25 mm Hg; a significant pre-capillary contribution to elevated mean pulmonary artery pressure was defined as a transpulmonary gradient (TPG) ≥12 mm Hg. Clinical endpoints were assessed at 2 years and included all-cause mortality and a composite of death, left ventricular assist device, or cardiac transplantation. RESULTS Patients with TPG ≥12 mm Hg were more likely to experience all-cause mortality (hazard ratio [HR]: 3.2; 95% confidence interval [CI]: 1.3 to 7.4; p = 0.009) and the composite outcome (HR: 3.0; 95% CI: 1.4 to 6.3; p = 0.004) compared with patients with TPG <12 mm Hg. After multivariate adjustment for hemodynamic, clinical, and echocardiographic variables, only TPG ≥12 mm Hg and baseline right ventricular (RV) dilation (RV end-diastolic dimension >42 mm) were associated with the composite clinical outcome (p = 0.05 and p = 0.04, respectively). CONCLUSIONS High TPG PH and RV dilation are independent predictors of adverse outcomes in patients with LVSD who are receiving CRT. RV pulmonary vascular dysfunction may be a therapeutic target in select patients receiving CRT.

Prognostic implication of baseline PR interval in cardiac resynchronization therapy recipients

BACKGROUND Prolongation of the baseline ECG PR interval is frequently encountered among cardiac resynchronization therapy (CRT) recipients. There are conflicting data regarding the association of a prolonged PR interval with long-term clinical outcome in this patient group. OBJECTIVE The purpose of this study was to compare clinical outcomes and response to CRT in patients with normal (<200 ms) vs prolonged (≥200 ms) baseline PR interval. METHODS In this study, 283 patients (normal PR interval: n = 158; prolonged PR interval: n = 125) with documented baseline intrinsic PR interval were followed for 3 years after CRT implantation. The study population consisted of 24.7% women (mean age 66 ± 13 years, left ventricular ejection fraction 24% ± 7%). RESULTS A Cox proportional hazard model identified baseline PR interval as a predictor of the composite end-point (all-cause mortality, heart failure hospitalization, left ventricular assist device implantation, and heart transplantation) in univariate analysis (hazard ratio [HR] 1.49, 95% confidence interval [CI] 1.02-2.17, P = .04) but not in multivariate analysis. It also predicted heart failure hospitalization in univariate (HR 1.6, 95% CI 1.1-2.4, P = .02) and multivariate analysis (HR 1.6, 95% CI 1.0-2.3, P = .03). A prolonged PR interval was associated with lower probability of reverse remodeling defined as ≥10% improvement in ejection fraction (64% vs 77%, P = .057), especially in patients with non-left bundle branch block ECG morphology (41% vs 68%, P = .03). CONCLUSION Among patients with CRT, a prolonged baseline PR interval is an independent predictor of worse prognosis and lower probability of reverse remodeling, especially for patients with non-left bundle branch block morphology on ECG.

Progressive ventricular dysfunction among nonresponders to cardiac resynchronization therapy: baseline predictors and associated clinical outcomes.

BACKGROUND Cardiac resynchronization therapy (CRT) nonresponders have poor outcomes. The significance of progressive ventricular dysfunction among nonresponders remains unclear. OBJECTIVE We sought to define predictors of and clinical outcomes associated with progressive ventricular dysfunction despite CRT. METHODS We conducted an analysis of 328 patients undergoing CRT with defibrillator for standard indications. On the basis of 6-month echocardiograms, we classified patients as responders (those with a ≥5% increase in ejection fraction) and progressors (those with a ≥5% decrease in ejection fraction), and all others were defined as nonprogressors. Coprimary end points were 3-year (1) heart failure, left ventricular assist device (LVAD), transplantation, or death and (2) ventricular tachycardia (VT) or ventricular fibrillation (VF). RESULTS Multivariable predictors of progressive ventricular dysfunction were aldosterone antagonist use (hazard ratio [HR] 0.23; P = .008), prior valve surgery (HR 3.3; P = .005), and QRS duration (HR 0.98; P = .02). More favorable changes in ventricular function were associated with lower incidences of heart failure, LVAD, transplantation, or death (70% vs 54% vs 33%; P < .0001) and VT or VF (66% vs 38% vs 28%; P = .001) for progressors, nonprogressors, and responders, respectively. After multivariable adjustment, progressors remained at increased risk of heart failure, LVAD, transplantation, or death (HR 2.14; P = .0029) and VT or VF (HR 2.03; P = .046) as compared with nonprogressors. Responders were at decreased risk of heart failure, LVAD, transplantation, or death (HR 0.44; P < .0001) and VT or VF (0.51; P = .015) as compared with nonprogressors. CONCLUSION Patients with progressive deterioration in ventricular function despite CRT represent a high-risk group of nonresponders at increased risk of worsened clinical outcomes.

Characteristics of Responders to Cardiac Resynchronization Therapy: The Impact of Echocardiographic Left Ventricular Volume

One‐third of patients who receive cardiac resynchronization therapy (CRT) are classified as nonresponders. Characteristics of responders to CRT have been studied in multiple clinical trials.