Prevalence and Correlates of Elevated NT-proBNP in Pregnant Women in the General U.S. Population.

BACKGROUND: Physiologic changes in N-terminal pro-B-type natriuretic peptide (NT-proBNP) across trimesters of pregnancy have not been well studied. OBJECTIVES: The authors aimed to measure NT-proBNP in adult women, by pregnancy status and trimester, in a nationally representative sample from the National Health and Nutrition Examination Survey 1999 to 2004. METHODS: We conducted a cross-sectional analysis of 2,134 women (546 pregnant) aged 20 to 40 years without a history of cardiovascular disease. RESULTS: Among pregnant women in the first trimester, the prevalence of elevated NT-proBNP (>125 pg/mL) was 20.0% (SE, 6.6%) compared to 2.4% (SE, 0.8%) among women in the third trimester and 8.0% among nonpregnant women. After adjustment for demographics and cardiovascular risk factors, NT-proBNP was 44% higher (absolute difference 26.4 [95% CI: 11.2-41.6] pg/mL) in the first trimester of pregnancy compared to nonpregnant women. Among pregnant women only, adjusted NT-proBNP was 46% lower (absolute difference -22.2 [95% CI: -36.9 to -7.5] pg/mL) in women in the third trimester compared to women in the first trimester. NT-proBNP was inversely associated with body mass index and with systolic blood pressure. CONCLUSIONS: Women in the first trimester of pregnancy had significantly higher NT-proBNP than those in the third trimester and compared to similarly aged nonpregnant women. The dynamic nature of NT-proBNP should be taken into consideration when ordering NT-proBNP lab tests in pregnant women.

Instituting a Curriculum for Cardio-Obstetrics Subspecialty Fellowship Training.

Maternal mortality is rising in the United States, and cardiovascular disease is the leading cause. Adverse pregnancy outcomes such as preeclampsia and gestational diabetes heighten the risk of cardiovascular complications during pregnancy and the peripartum period and are associated with long-term cardiovascular risks. The field of cardio-obstetrics is a subspecialty within adult cardiology that focuses on the management of women with or at high risk for heart disease who are considering pregnancy or have become pregnant. There is growing recognition of the need for more specialists with dedicated expertise in cardio-obstetrics to improve the cardiovascular care of this high-risk patient population. Current recommendations for cardiovascular fellowship training programs accredited by the Accreditation Council for Graduate Medical Education involve establishing core competency in the knowledge of managing heart disease in pregnancy. However, little granular detail is available of what such training should entail, which can lead to knowledge gaps. Additionally, dedicated advanced subspecialty training in this area is not commonly offered. Multidisciplinary collaborative teams have been shown to improve outcomes in cardiac patients during pregnancy, and cardiovascular fellows-in-training interested in cardio-obstetrics should have the opportunity to participate in and contribute to a pregnancy heart team. In this document, we describe a proposed specialized cardio-obstetrics training pathway that could serve to adequately prepare trainees to competently and comprehensively care for women with cardiovascular disease before, during, and after pregnancy.

Plasma Proprotein Convertase Subtilisin/kexin Type 9 (PCSK9) in the Acute Respiratory Distress Syndrome.

Background: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a serine protease that is a mediator of the immune response to sepsis. PCSK9 is also highly expressed in pneumocytes and pulmonary endothelial cells. We hypothesized that serum PCSK9 levels would be associated with death and ICU outcomes in patients with ARDS. Methods: Using data and plasma samples from the NIH BioLINCC data repository, we assembled a cohort of 1,577 patients with the acute respiratory distress syndrome (ARDS) enrolled in two previously completed clinical trials, EDEN and SAILS. We measured PCSK9 levels in plasma within 24 h of intubation using commercially available ELISA kits (R&D Systems). We assessed the association of PCSK9 with mortality using Cox proportional hazard models. We also assessed clinical factors associated with PCSK9 level and the association of PCSK9 with the number of days free of mechanical ventilation and days free of ICU care. Results: In 1,577 ARDS patients, median age was 53 years (IQR 42-65 years) and median APACHE III score 91 (72-111) connoting moderate critical illness. PCSK9 levels were 339.3 ng/mL (IQR 248.0-481.0). In multivariable models, race, cause of ARDS, body mass index, pre-existing liver disease, body temperature, sodium, white blood cell count and platelet count were associated with PCSK9 level. Presence of sepsis, use of vasopressors and ventilator parameters were not associated with PCSK9 level. PCSK9 levels were not associated with in-hospital mortality (HR per IQR 0.96, 95% CI 0.84-1.08, P = 0.47). Higher PCSK9 levels were associated with fewer ICU and ventilator free days. Conclusions: Plasma PCSK9 is not associated with mortality in ARDS, however higher PCSK9 levels are associated with secondary outcomes of fewer ICU free and ventilator free days. Clinical factors associated with PCSK9 in ARDS are largely unmodifiable. Further research to define the mechanism of this association is warranted.

Atrial fibrillation is an independent risk factor for heart failure hospitalization in heart failure with preserved ejection fraction.

AIMS: Atrial fibrillation (AF) is a common comorbid condition in heart failure with preserved ejection fraction (HFpEF). The effect of AF on heart failure (HF) exacerbation in HFpEF has not been well described. This study investigated how AF modifies the clinical trajectory of HFpEF patients after hospitalization for decompensated HF. METHODS AND RESULTS: We stratified HFpEF subjects by AF diagnosis and performed longitudinal analysis to compare risk for HF hospitalization after index hospitalization for decompensated HF. All-cause mortality, 30 day all-cause readmissions, and response to inpatient diuresis were also evaluated. Of 90 subjects enrolled, 35.6% (n = 32) had AF. Subjects with AF were older (72.5 vs. 60.5 years; P < 0.01), more often male (46.9% vs. 24.1%; P = 0.03), and had greater left atrial diameter (4.9 vs. 3.8 cm; P < 0.01) compared with those without AF. Subjects with AF had a higher risk for HF hospitalization than their counterparts without AF (P = 0.02); this relationship remained significant following multivariable competing risk regression with propensity score weighting (hazard ratio 2.53, P = 0.04 and hazard ratio 2.91, P = 0.04, with overlap and inverse probability weighting, respectively). Although having AF appeared to increase the risk of all-cause hospital readmission within 30 days of discharge (37.5% vs. 17.5%; P = 0.036), this relationship failed to remain significant following propensity score adjustment for clinical covariates. CONCLUSIONS: Atrial fibrillation is an independent risk factor for HF rehospitalization in HFpEF. Further understanding of the interplay between AF and HFpEF will be critical to guide the selection of appropriate rhythm management strategies in this population.

The Trajectory of Lipoprotein(a) During the Peri- and Early Postinfarction Period and the Impact of Proprotein Convertase Subtilisin/Kexin Type 9 Inhibition.

Lipoprotein(a), or Lp(a), levels and the effect of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition on Lp(a) during the peri-infarction and early postinfarction period are not well characterized. This study aimed to describe the trajectory of Lp(a), as well as the effect of PCSK9 inhibition on that trajectory during the peri-infarction and early postinfarction period. Lp(a) levels were obtained within 24 hours of hospital admission as well as within 24 hours of hospital discharge and at 30 days from 74 participants who presented with a NSTEMI (troponin I >5 ng/ml) or with a STEMI and were enrolled in 2 randomized, double-blind trials of evolocumab and placebo (Evolocumab in Acute Coronary Syndrome [EVACS I]; ClinicalTrials.gov, NCT03515304 and Evolocumab in Patients With STEMI [EVACS II]; ClinicalTrials.gov Identifier: NCT04082442). There was a significant increase from the pretreatment level in the placebo-treated patients, from 64 (41,187) nmol/L to 80 (47, 172) nmol/L at hospital discharge and to 82 (37, 265) at 30 days. This was primarily driven by the results from participants with high Lp(a) at hospital admission (>75 nmol/L) in whom the median increase was 28% as compared with a 10% increase in those with pretreatment Lp(a) of <75 nmol/L. In contrast, there was no significant change from the pretreatment level in the evolocumab-treated patients regardless of pretreatment Lp(a) levels. In conclusion, Lp(a) rises during the peri-infarction and early postinfarction period in patients with acute myocardial infarction. The increase was prevented by a single dose of subcutaneous evolocumab given within 24 hours of hospital admission.

Rate Versus Rhythm Control in Heart Failure Patients with Post-Operative Atrial Fibrillation After Cardiac Surgery.

BACKGROUND: Whether rhythm control for post-operative atrial fibrillation after cardiac surgery (POAF) is superior to rate control in patients with heart failure or systolic dysfunction (HF) is not known. METHODS: We performed a post-hoc analysis of a trial by the Cardiothoracic Surgical Trials Network, which randomized patients with POAF after cardiac surgery to rate control or rhythm control with amiodarone/cardioversion. We assessed subgroups of trial participants defined by heart failure/cardiomyopathy history or left ventricular ejection fraction (LVEF) < 50%. We conducted a stratified analysis in patients with and without HF to explore outcomes of rhythm versus rate control strategy. RESULTS: Of 523 subjects with POAF after cardiac surgery, 131 (25%) had HF. 49% of HF patients were randomized to rhythm control. In HF patients, rhythm control was associated with less atrial fibrillation within the first 7 days. There were no differences in rhythm at 30- and 60-day follow-up. In the HF group, there were significantly more subjects with AF < 48 hours in the rhythm control group compared to rate control group- 68.8% compared to 46.3%, P=0.009. By comparison, in the non-HF stratum, 54.4% of the rate control group had AF < 48 hours compared to 63.5% of the rhythm control group (P=0.067).), though there was no significant interaction of heart failure with cardiac rhythm at 7 days (Pinteraction 0.16). CONCLUSION: Rhythm control for HF patients with POAF after cardiac surgery increases early restoration of sinus rhythm. Rate and rhythm control are both reasonable for HF patients with AF after cardiac surgery.

Cardiovascular and Obstetric Delivery Complications in Pregnant Women With Valvular Heart Disease.

Women with valvular heart disease may be more likely to have adverse obstetric and cardiovascular complications during pregnancy. Most current recommendations focus on stenotic lesions with less guidance regarding regurgitant lesions. We aimed to compare adverse events at delivery for women with various stenotic and regurgitant valvular diseases. We used the 2016 to 2018 National Inpatient Sample data to compare demographics, comorbidities, and obstetric and cardiovascular complications during delivery hospitalizations. After adjusting for clinical and socioeconomic factors, logistic regression was performed to investigate associations between valvular disease and outcomes. Among >11.2 million deliveries, 20,349 were in women with valvular disease. Women with valvular disease were older, had longer length of stays, and higher costs associated with delivery. They had higher prevalence of underlying cardiovascular comorbidities compared with women without valvular disease (hypertension: 5.1 vs 0.25%; pulmonary hypertension: 7.0 vs <0.1%). At delivery, they had higher adjusted odds of obstetric events including preeclampsia and/or eclampsia (aOR 1.9 [1.8 to 2.2]) and intrapartum/postpartum hemorrhage (aOR 1.4 [1.2 to 1.6]), and cardiovascular events including peripartum cardiomyopathy (aOR 65 [53 to 78]), pulmonary edema (aOR 17 [13 to 22]), acute ischemic heart disease (aOR 19 [12 to 30]) and arrhythmias (aOR 22 [19 to 27]). There were valve lesion-specific differences in the magnitude of risk but both stenotic and regurgitant lesions were associated with elevated risk of cardiovascular complications. In conclusion, pregnant women with stenotic and regurgitant valvular disease have a greater burden of cardiovascular comorbidities and increased odds of obstetric and cardiovascular events at delivery. These women may benefit from specialized care from a Cardio-Obstetrics team.

Presentation and outcomes of sepsis in the cardiac intensive care unit.

The prevalence of sepsis is increasing in subspecialty intensive care units, including the cardiac intensive care unit (CICU). The clinical characteristics and outcomes of CICU patients with sepsis are not well understood. We conducted a retrospective cohort study of sepsis patients in the CICU compared to other ICUs using the PROGRESS registry. CICU-sepsis patients were older with fewer acute organ failures (median 2 v. 3, p < 0.001), lower SOFA scores (median 7 v. 9, p < 0.001), and more comorbidities. The use of fluid resuscitation, mechanical ventilation, and renal replacement were similar. Mortality was 47.3% for CICU-sepsis patients compared to 43.6% for sepsis patients in other ICU (P = 0.37). We conclude that, in a prior cohort of septic patients, sepsis in CICU patients had outcomes that are comparably poor to sepsis in other ICUs. Septic CICU patients presented with fewer acute organ failures, but more chronic comorbidities. Contemporary data as well as novel interventions and investigations targeted specifically to cardiac patients with sepsis should be prioritized.

Corrigendum to "The Kaleidoscope Model of Integrative Healthcare as a collaborative paradigm for cardiology and chiropractic: a call to action" [Integr Med Res 2018; 7(1): 1-8].

[This corrects the article DOI: 10.1016/j.imr.2018.01.009.].

Advanced Respiratory Support in the Contemporary Cardiac ICU.

The medical complexity and critical care needs of patients admitted to cardiac ICUs are increasing, and prospective studies examining the underlying cardiac and noncardiac diagnoses, the management strategies, and the prognosis of cardiac ICU patients with respiratory failure are needed. DESIGN: Prospective cohort study. SETTING: The Critical Care Cardiology Trials Network is a research collaborative of cardiac ICUs across the United States and Canada. PATIENTS: We included all medical cardiac ICU admissions at 25 cardiac ICUs during two consecutive months annually at each center from 2017 to 2019. MEASUREMENTS: We evaluated the use of advanced respiratory therapies including invasive mechanical ventilation, noninvasive ventilation, and high-flow nasal cannula versus no advanced respiratory support across admission diagnoses and the association with in-hospital mortality. MAIN RESULTS: Of 8,240 cardiac ICU admissions, 1,935 (23.5%) were treated with invasive mechanical ventilation, 573 (7.0%) with noninvasive ventilation, and 281 (3.4%) with high-flow nasal cannula. Admitting diagnoses among those with advanced respiratory support were diverse including general medical problems in patients with heart disease as well as primary cardiac problems. In-hospital mortality was higher in patients who received invasive mechanical ventilation (38.1%; adjusted odds ratio, 2.53; 2.02-3.16) and noninvasive ventilation or high-flow nasal cannula (8.8%; adjusted odds ratio, 2.25; 1.73-2.93) compared with patients without advanced respiratory support (4.6%). Reintubation rate was 7.6%. The most common variables associated with respiratory insufficiency included heart failure, infection, chronic obstructive pulmonary disease, and pulmonary vascular disease. CONCLUSIONS: One-third of cardiac ICU admissions receive respiratory support with associated increased mortality. These data provide benchmarks for quality improvement ventures in the cardiac ICU, inform cardiac critical care training and staffing patterns, and serve as foundation for future studies aimed at improving outcomes.

Highest Obesity Category Associated With Largest Decrease in N-Terminal Pro-B-Type Natriuretic Peptide in Patients Hospitalized With Heart Failure With Preserved Ejection Fraction.

Background Heart failure with preserved ejection fraction (HFpEF) constitutes half of hospitalized heart failure cases and is commonly associated with obesity. The role of natriuretic peptide levels in hospitalized obese patients with HFpEF, however, is not well defined. We sought to evaluate change in NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels by obesity category and related clinical outcomes in patients with HFpEF hospitalized for acute heart failure. Methods and Results A total of 89 patients with HFpEF hospitalized with acute decompensated heart failure were stratified into 3 obesity categories: nonobese (body mass index [BMI] <30.0 kg/m2, 19%), obese (BMI 30.0-39.9 kg/m2, 29%), and severely obese (BMI ≥40.0 kg/m2, 52%), and compared for percent change in NT-proBNP during hospitalization and clinical outcomes. Clinical characteristics were compared between patients with normal NT-proBNP (≤125 pg/mL) and elevated NT-proBNP. Admission NT-proBNP was inversely related to BMI category (nonobese, 2607 pg/mL [interquartile range, IQR: 2112-5703]; obese, 1725 pg/mL [IQR: 889-3900]; and severely obese, 770.5 pg/mL [IQR: 128-1268]; P<0.01). Severely obese patients had the largest percent change in NT-proBNP with diuresis (-64.8% [95% CI, -85.4 to -38.9] versus obese -40.4% [95% CI, -74.3 to -12.0] versus nonobese -46.9% [95% CI, -57.8 to -37.4]; P=0.03). Nonobese and obese patients had significantly worse 1-year survival compared with severely obese patients (63% versus 76% versus 95%, respectively; P<0.01). Patients with normal NT-proBNP (13%) were younger, with higher BMI, less atrial fibrillation, and less structural heart disease than those with elevated NT-proBNP. Conclusions In hospitalized patients with HFpEF, NT-proBNP was inversely related to BMI with the largest decrease in NT-proBNP seen in the highest obesity category. These findings have implications for the role of NT-proBNP in the diagnosis and assessment of treatment response in obese patients with HFpEF.

Incidence, Predictors, and Outcomes of Failure of Noninvasive Ventilation in Acute Heart Failure Hospitalization.

BACKGROUND: Some patients with acute heart failure (AHF) who are treated initially with noninvasive ventilation (NIV) will require endotracheal intubation, which indicates NIV failure. The incidence and prognosis of NIV failure in patients with AHF are not well characterized. METHODS: Using the National In-Patient Sample (NIS), we conducted a retrospective cohort study of subjects hospitalized with AHF between 2008 and 2014 who were treated with NIV within 24 h of hospital admission. We determined predictors of NIV failure and determined the association between NIV failure and in-hospital mortality using Cox proportional hazard models. RESULTS: Of 279,534 subjects hospitalized with AHF and treated with NIV, 4,257 (1.52%) failed NIV and required intubation. Cardiogenic shock (odds ratio 8.79, 95% CI 6.89-11.2) and in-hospital arrest (odds ratio 24.9, 95% CI 18.71-33.14) were associated with NIV failure. In-hospital mortality was 26.5% for NIV failure compared to 5.6% for those without NIV (P < .001). After adjustment for demographics, comorbidities, cardiogenic shock, and in-hospital arrest, NIV failure was associated with nearly a 2-fold risk of in-hospital mortality (odds ratio 1.95, 95% CI 1.59-2.40). CONCLUSIONS: Intubation after initial NIV treatment was required in 1.5% of subjects hospitalized with AHF and treated with NIV, and was associated with high in-hospital mortality. These findings can guide future prospective interventional trials and quality improvement ventures.

Incidence, predictors and prognosis of respiratory support in non-ST segment elevation myocardial infarction.

BACKGROUND: The incidences of invasive mechanical ventilation and non-invasive ventilation among patients with non-ST segment elevation myocardial infarction and associated prognosis are not well characterized. METHODS: We conducted a retrospective cohort study of patients with admission diagnosis of non-ST segment elevation myocardial infarction using the US National Inpatient Sample database between 2002-2014. The exposure variable was invasive mechanical ventilation or non-invasive ventilation within 24 h of admission, compared to no respiratory support. The primary outcome was in-hospital mortality. We determined the association between respiratory support and mortality using Cox proportional hazard models. RESULTS: A total of 4,152,421 non-ST segment elevation myocardial infarction hospitalizations were identified, among whom 1.3% required non-invasive ventilation and 1.9% required invasive mechanical ventilation. Non-invasive ventilation use increased over time (0.4% in 2002 to 2.4% in 2014, p<0.001) while there was no definite trend in invasive mechanical ventilation use. Revascularization was lower for non-ST segment elevation myocardial infarction hospitalizations including invasive mechanical ventilation (23.9%) and non-invasive ventilation (14.5%) compared to 36.5% of those without respiratory support (p<0.001). In-hospital mortality was 3.1% for non-ST segment elevation myocardial infarction without respiratory support compared to 9.2% with non-invasive ventilation (adjusted hazard ratio 1.86, 95% confidence interval 1.74-1.98) and 37.2% with invasive mechanical ventilation (adjusted hazard ratio 3.03, 95% confidence interval 2.88-3.19). Mortality for non-ST segment elevation myocardial infarction-non-invasive ventilation is improving over time while mortality for non-ST segment elevation myocardial infarction-invasive mechanical ventilation is increasing over time. CONCLUSION: Mechanical respiratory support in non-ST segment elevation myocardial infarction is used in an important minority of cases, is increasing and is independently associated with mortality. Studies of the optimal management of acute coronary syndrome complicated by respiratory failure are needed to improve outcomes.

Usefulness of Noninvasively Measured Pulse Amplitude Changes During the Valsalva Maneuver to Identify Hospitalized Heart Failure Patients at Risk of 30-Day Heart Failure Events (from the PRESSURE-HF Study).

The pulse amplitude ratio (PAR), the ratio of pulse pressure at the end of the Valsalva maneuver to before the onset, correlates with cardiac filling pressure. We have developed a handheld device that uses finger photoplethysmography to measure PAR and estimate left ventricular end diastolic pressure (LVEDP). Patients hospitalized with heart failure (HF) performed three 10-second trials of a standardized Valsalva maneuver (at 20 mm Hg measured via pressure transducer), while photoplethysmography waveforms were recorded, at admission and discharge. Combined primary outcome was 30-day HF hospitalization, intravenous diuresis, or death. Fifty-two subjects had discharge PAR testing; 12 met the primary outcome. Median PAR on admission was 0.55 (interquartile range: 0.40 to 0.70, n = 48) and on discharge was 0.50 (interquartile range: 0.36 to 0.69). Mean PAR-estimated LVEDP was significantly higher in subjects that had an event (20.2 vs 16.9 mm Hg, p = 0.043). Subjects with PAR-estimated LVEDP >19.5 mm Hg had an event rate hazard ratio of 4.57 (95% confidence interval 1.37, 15.19, p = 0.013) compared with patients with LVEDP 19.5 mm Hg or below, with significantly lower 30-day event-free survival (log-rank p = 0.006). In conclusion, noninvasively estimated LVEDP using the pulse amplitude response to a Valsalva maneuver in patients hospitalized for HF changes with diuresis and identifies patients at high risk for 30-day HF events. Detection of elevated filling pressures before hospital discharge may be useful in guiding HF management to reduce HF events.

In-Hospital Management and Outcomes of Patients With Acute Myocardial Infarction and Influenza.

Patients with influenza infection are at increased risk of acute myocardial infarction (AMI). There are limited data on the short-term prognosis and management of patients with AMI and concomitant influenza. We examined the National Inpatient Sample from 2010 to 2014 for adult patients with a diagnosis of AMI. Patients were stratified into those with or without concomitant influenza. In-hospital therapies and outcomes were compared between groups in unadjusted and adjusted analyses. Standardized differences of >10% and p values <0.05 were considered significant. Propensity matching was performed using a caliper radius of 0.01*sigma. Of 4,285,641 patients with a discharge diagnosis of AMI, 12,830 had concomitant influenza. Patients with influenza were older, had a higher burden of co-morbidities, and more often presented with non-ST elevation AMI (90% vs 74%) as compared with those without influenza. Coronary angiography (23% vs 54%) and revascularization (11% vs 41%) were less often pursued in AMI patients with influenza. Patients with AMI and influenza had elevated in-hospital mortality (14%) and multiorgan failure (33%). In a propensity-matched analysis of 23,415 patients, in-hospital mortality (odds ratio [OR] 1.26; p = 0.01), acute kidney injury (OR 1.36; p <0.01), multiorgan failure (OR 1.81; p <0.01), length-of-stay, and hospital costs were significantly higher in those with influenza. In conclusion, patients with AMI and concomitant influenza have an adverse in-hospital prognosis as compared with those without influenza.

Crossing the Bridge to Heart Transplantation: Biventricular Impella to Support an Unstable LVAD Patient.

We report the first case of a patient with a durable left ventricular assist device admitted with cardiogenic shock and managed with biventricular Impella support as a successful bridge to heart transplantation. (Level of Difficulty: Advanced.).