Peripartum cardiomyopathy (PPCM) remains a major cause of maternal morbidity and mortality.
This study sought to prospectively evaluate recovery of the left ventricular ejection fraction (LVEF) and ...clinical outcomes in the multicenter IPAC (Investigations of Pregnancy Associated Cardiomyopathy) study.
We enrolled and followed 100 women with PPCM through 1 year post-partum. The LVEF was assessed by echocardiography at baseline and at 2, 6, and 12 months post-partum. Survival free from major cardiovascular events (death, transplantation, or left ventricular LV assist device) was determined. Predictors of outcome, particularly race, parameters of LV dysfunction (LVEF), and remodeling (left ventricular end-diastolic diameter LVEDD) at presentation, were assessed by univariate and multivariate analyses.
The cohort was 30% black, 65% white, 5% other; the mean patient age was 30 ± 6 years; and 88% were receiving beta-blockers and 81% angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. The LVEF at study entry was 0.35 ± 0.10, 0.51 ± 0.11 at 6 months, and 0.53 ± 0.10 at 12 months. By 1 year, 13% had experienced major events or had persistent severe cardiomyopathy with an LVEF <0.35, and 72% achieved an LVEF ≥0.50. An initial LVEF <0.30 (p = 0.001), an LVEDD ≥6.0 cm (p < 0.001), black race (p = 0.001), and presentation after 6 weeks post-partum (p = 0.02) were associated with a lower LVEF at 12 months. No subjects with both a baseline LVEF <0.30 and an LVEDD ≥6.0 cm recovered by 1 year post-partum, whereas 91% with both a baseline LVEF ≥0.30 and an LVEDD <6.0 cm recovered (p < 0.00001).
In a prospective cohort with PPCM, most women recovered; however, 13% had major events or persistent severe cardiomyopathy. Black women had more LV dysfunction at presentation and at 6 and 12 months post-partum. Severe LV dysfunction and greater remodeling at study entry were associated with less recovery. (Investigations of Pregnancy Associated Cardiomyopathy IPAC; NCT01085955).
Several clinical prediction schemes for right ventricular failure (RVF) risk after left ventricular assist device (LVAD) implantation have been developed in both the pulsatile- and continuous-flow ...LVAD eras. The performance of these models has not been evaluated systematically in a continuous-flow LVAD cohort.
We evaluated 6 clinical RVF prediction models (Michigan, Penn, Utah, Kormos et al, CRITT, Pittsburgh Decision Tree) in 116 patients (age 51 ± 13 years; 41.4% white and 56.0% black; 66.4% men; 56.0% bridge to transplant, 37.1% destination therapy, 17.4% bridge to decision) who received a continuous-flow LVAD (HeartMate II: 79 patients, HeartWare: 37 patients) between 2008 and 2013.
Overall, 37 patients (31.9%) developed RVF, defined: as pulmonary vasodilator use for ≥48 hours or inotrope use for ≥14 days post-operatively; re-institution of inotropes; multi-organ failure due to RVF; or need for mechanical RV support. Median (Quartile 1 to Quartile 3) time to initial discontinuation of inotropes was 6 (range 4 to 8) days. Among scores, the Michigan score reached significance for RVF prediction but discrimination was modest (C = 0.62 95% CI 0.52 to 0.72, p = 0.021; positive predictive value PPV 60.0%; negative predictive value NPV 75.8%), followed by CRITT (C = 0.60 95% CI 0.50 to 0.71, p = 0.059; PPV 40.5%; NPV 72.2%). Other models did not significantly discriminate RVF. The newer, INTERMACS 3.0 definition for RVF, which includes inotropic support beyond 7 days, was reached by 57 patients (49.1%). The Kormos model performed best with this definition (C = 0.62 95% CI 0.54 to 0.71, p = 0.005; PPV 64.3%; NPV 59.5%), followed by Penn (C = 0.61), Michigan (C = 0.60) and CRITT (C = 0.60), but overall score performance was modest.
Current schemes for post-LVAD RVF risk prediction perform only modestly when applied to external populations.
Left atrial (LA) structural and functional abnormalities may be subclinical phenotypes, which identify individuals at increased risk of adverse outcomes.
Maximum LA volume (LAmax) and LA emptying ...fraction (LAEF) were measured via cardiac magnetic resonance imaging in 1802 participants in the Dallas Heart Study. The associations of LAEF and LAmax indexed to body surface area (LAmax/BSA) with traditional risk factors, natriuretic peptide levels, and left ventricular (LV) structure end-diastolic volume (EDV) and concentricity(0.67) (mass/EDV(0.67)) and function (ejection fraction) were assessed using linear regression analysis. The incremental prognostic value of LAmax/BSA and LAEF beyond traditional risk factors, LV ejection fraction, and LV mass was assessed using the Cox proportional-hazards model. Both increasing LAmax/BSA and decreasing LAEF were associated with hypertension and natriuretic peptide levels (P < 0.05 for all). In multivariable analysis, LAmax/BSA was most strongly associated with LV end-diastolic volume/BSA, while LAEF was strongly associated with LV ejection fraction and concentricity(0.67). During a median follow-up period of 8.1 years, there were 81 total deaths. Decreasing LAEF hazard ratio (HR) per 1 standard deviation (SD) (8.0%): 1.56 (1.32-1.87) but not increasing LAmax/BSA HR per 1 SD (8.6 mL/m(2)): 1.14 (0.97-1.34) was independently associated with mortality. Furthermore, the addition of LAEF to a model adjusting Framingham risk score, diabetes, race, LV mass, and ejection fraction improved the c-statistic (c-statistics: 0.78 vs. 0.77; P < 0.05, respectively), whereas the addition of LAmax/BSA did not (c-statistics: 0.76, P = 0.20).
In the general population, both LAmax/BSA and LAEF are important subclinical phenotypes but LAEF is superior and incremental to LAmax/BSA.
HVAD: The ENDURANCE Supplemental Trial Milano, Carmelo A.; Rogers, Joseph G.; Tatooles, Antone J. ...
JACC. Heart failure,
September 2018, 2018-Sep, 2018-09-00, 20180901, Letnik:
6, Številka:
9
Journal Article
Recenzirano
Odprti dostop
The aim of this study was to prospectively evaluate the impact of blood pressure management on stroke rates in patients receiving the HeartWare HVAD System.
The ENDURANCE trial demonstrated ...noninferiority of the HeartWare HVAD System versus control (HeartMate II) in patients with advanced heart failure ineligible for heart transplantation. However, stroke was more common in HVAD subjects. Post hoc analyses demonstrated increased mean arterial blood pressure as a significant independent risk factor for stroke.
The ENDURANCE Supplemental Trial was a prospective, multicenter evaluation of 465 patients with advanced heart failure ineligible for transplantation, randomized 2:1 to HVAD (n = 308) or control (n = 157). The primary endpoint was the 12-month incidence of transient ischemic attack or stroke with residual deficit 24 weeks post-event. Secondary endpoints included the composite of freedom from death, disabling stroke, and need for device replacement or urgent transplantation, as well as comparisons of stroke or transient ischemic attack rates in HVAD cohorts in ENDURANCE Supplemental and ENDURANCE.
The enhanced blood pressure protocol significantly reduced mean arterial blood pressure. The primary endpoint was not achieved (14.7% with HVAD vs. 12.1% with control, noninferiority margin 6% p = 0.14). However, the secondary composite endpoint demonstrated superiority of HVAD (76.1%) versus control (66.9%) (p = 0.04). The incidence of stroke in HVAD subjects was reduced 24.2% in ENDURANCE Supplemental compared with ENDURANCE (p = 0.10), and hemorrhagic cerebrovascular accident was reduced by 50.5% (p = 0.02).
The ENDURANCE Supplemental Trial failed to demonstrate noninferiority of HVAD versus control regarding the pre-specified primary endpoint. However, the trial confirmed that BP management is associated with reduced stroke rates in HVAD subjects. HVAD subjects, relative to control subjects, more commonly achieved the composite endpoint (freedom from death, disabling stroke, and device replacement or urgent transplantation). (A Clinical Trial to Evaluate the HeartWare™ Ventricular Assist System ENDURANCE SUPPLEMENTAL TRIAL DT2; NCT01966458)
Display omitted
Background "Financial toxicity" is a concern for patients, but little is known about how patients consider out-of-pocket cost in decisions. Sacubitril-valsartan provides a contemporary scenario to ...understand financial toxicity. It is guideline recommended for heart failure with reduced ejection fraction, yet out-of-pocket costs can be considerable. Methods and Results Structured interviews were conducted with 49 patients with heart failure with reduced ejection fraction at heart failure clinics and inpatient services. Patient opinions of the drug and its value were solicited after description of benefits using graphical displays. Descriptive quantitative analysis of closed-ended responses was conducted, and qualitative descriptive analysis of text data was performed. Of participants, 92% (45/49) said that they would definitely or probably switch to sacubitril-valsartan if their physician recommended it and out-of-pocket cost was $5 more per month than their current medication. Only 43% (21/49) would do so if out-of-pocket cost was $100 more per month ( P<0.001). At least 40% across all income categories would be unlikely to take sacubitril-valsartan at $100 more per month. Participants exhibited heterogeneous approaches to cost in decision making and varied on their use and interpretation of probabilistic information. Few (20%) participants stated physicians had initiated a conversation about cost in the past year. Conclusions Out-of-pocket cost variation reflective of contemporary cost sharing substantially influenced stated willingness to take sacubitril-valsartan, a guideline-recommended therapy with mortality benefit. These findings suggest a need for cost transparency to promote shared decision making. They also demonstrate the complexity of cost discussion and need to study how to incorporate out-of-pocket cost into clinical decisions.
Objectives This study sought to examine the frequency and hemodynamic correlates of shortness of breath when bending forward, a symptom we have termed “bendopnea.” Background Many heart failure ...patients describe bendopnea such as when putting on their shoes. This symptom has not previously been characterized. Methods We conducted a prospective study of 102 subjects with systolic heart failure referred for right-heart catheterization. Time to onset of bendopnea was measured prior to catheterization. Forty-six subjects also underwent hemodynamic assessment when sitting and bending. Hemodynamic profiles were assigned on the basis of whether pulmonary capillary wedge pressure (PCWP) was ≥22 mm Hg and cardiac index (CI) was ≤2.2 l/min/m2. Results Bendopnea was present in 29 of 102 (28%) subjects with median (25th, 75th percentiles) time to onset of 8 (7, 11) seconds. Subjects with bendopnea had higher supine right atrial pressure (RAP) (p = 0.001) and PCWP (p = 0.0004) than those without bendopnea but similar CI (p = 0.2). RAP and PCWP increased comparably in subjects with and without bendopnea when bending, but CI did not change. In those with, versus without, bendopnea, there was more than a 3-fold higher frequency of a supine hemodynamic profile consisting of elevated PCWP with low CI (55% vs. 16%, respectively, p < 0.001) but no association with a profile of elevated PCWP with normal CI (p = 0.95). Conclusions Bendopnea is mediated via a further increase in filling pressures during bending when filling pressures are already high, particularly if CI is reduced. Awareness of bendopnea should improve noninvasive assessment of hemodynamics in subjects with heart failure.
Insertion of a left ventricular assist device (LVAD) is an accepted therapy for advanced heart failure patients. However, the effects on end-organ perfusion, including cerebral autoregulation, are ...unclear in the presence of reduced pulsatility. Therefore, the objective of this study was to determine whether cerebral autoregulation is impaired in patients with continuous-flow (CF) LVADs.
Dynamic cerebral autoregulation was assessed in both time-domain (autoregulatory index) and frequency-domain (transfer function analysis) analyses in 9 CF-LVAD subjects, 5 pulsatile LVAD subjects and 10 healthy controls, by evaluating mean arterial pressure (MAP) and cerebral blood flow velocity (CBFV) during a sit-stand maneuver at 0.05 Hz (10-second sit, 10-second stand). The autoregulatory index was calculated as the percent change in mean CBFV per mm Hg change in MAP.
The magnitude of oscillation in MAP and CBFV was greater in subjects with pulsatile LVADs than either CF-LVADs or healthy controls (p = 0.065 for MAP, p = 0.004 for CBFV). The autoregulatory index and transfer function gain were similar among groups, indicating that dynamic cerebral autoregulation is preserved among patients with CF-LVADs.
Cerebral blood flow in patients with CF-LVADs is comparable to that of healthy controls across a range of blood pressures. Patients with pulsatile devices have greater oscillations in MAP and CBFV. However, dynamic cerebral autoregulation is preserved among subjects with either type of device. Thus, the reduction in pulsatility afforded by CF-LVADs does not impair normal autoregulatory processes.
Abstract Background Left ventricular assist device (LVAD) support as bridge to recovery (BTR) is uncommon for subjects with chronic heart failure. Myocardial recovery is more evident in recent onset ...nonischemic cardiomyopathy (ROCM); however, the prevalence of BTR in this subset has not been addressed. Methods and Results We examined the use of LVAD support for subjects with ROCM in the Intervention in Myocarditis and Acute Cardiomyopathy 2 (IMAC2) study. The overall cohort (n = 373) was 38% female, 21% black, with a mean age of 45 ± 14 years. LVAD support was used in 3.8% (n = 14, 43% female, age 32 ± 10). Of LVAD subjects, 57% (8/14) were BTR, including 73% (8/11) of subjects with symptoms ≤4 months at the time of support. Left ventricular end-diastolic diameter (LVEDD) was smaller in BTR than nonrecovered (NR) subjects ( P = .04). Myocardial inflammation was more common in BTR (75% versus 0%, P = .005), whereas fibrosis was less evident (25% versus 100%, P = .005). Of BTR subjects, 7/8 (87.5%) were alive and free of transplant with median follow-up of 19 months. Conclusion In a multicenter registry of ROCM, BTR was common and occurred in the majority of subjects requiring LVAD support. Histology and LVEDD may assist in predicting potential for BTR in ROCM.
Abstract Objectives This study sought to estimate the rate of progression to Stage D heart failure (HF) among outpatients with Stage C HF and to identify risk factors for progression. Background The ...pool of patients who may be candidates for advanced HF therapies is growing. Methods We estimated 3-year progression to clinically determined Stage D HF and competing mortality among 964 outpatients with Stage C heart failure with reduced ejection fraction (HFrEF), where ejection fraction is ≤40%. Results The mean age of patients was 62 ± 15 years; 35% were women; 47% were white; 46% were black, and 7% were of other races; median baseline ejection fraction was 28% (25th to 75th percentile: 20% to 35%); and 47% had ischemic heart disease. After 3.0 years (25th to 75th percentile: 1.7 to 3.2 years), 112 patients progressed to Stage D (3-year incidence: 12.2%; 95% confidence interval CI: 10.2% to 14.6%; annualized: 4.5%; 95% CI: 3.8% to 5.5%), and 116 patients died before progression (3-year competing mortality: 12.9%; annualized: 4.7%; 95% CI: 3.9% to 5.6%). By 3 years, 25.1% of patients (95% CI: 22.2% to 28.1%) had either progressed to Stage D or died (annualized: 9.2%; 95% CI: 8.1% to 10.5%). Annualized progression rates were higher in black versus white patients (6.3% vs. 2.7%, respectively; p < 0.001), nonischemic versus ischemic patients (6.1% vs. 2.9%, respectively; p < 0.001), and in New York Heart Association functional class III to IV versus I to II patients (7.5% vs. 1.9%, respectively; p < 0.001) but were similar for men and women (4.7% vs. 4.2%, respectively; p = 0.53). Lower ejection fraction and blood pressure, renal and hepatic dysfunction, and chronic lung disease rates were additional predictors of progression. Predictors of competing mortality were different from those of disease progression. Conclusions Among patients with Stage C HFrEF receiving care in a referral center, 4.5% progressed to Stage D HF each year, with earlier progression among black and nonischemic patients. These findings have implications for healthcare planning and resource allocation for these patients.
PDF
