Ambulatory Heart Failure Research Articles

A MULTI-CENTRE STUDY EXAMINING THE ASSOCIATION BETWEEN NATRIURETIC PEPTIDES AND MORTALITY IN PATIENTS WITH A LEFT VENTRICULAR ASSIST DEVICE

BACKGROUND In patients with advanced heart failure, a left ventricular assist device (LVAD) offers improved survival and quality of life. NTproBNP is commonly measured during routine follow-up in patients with a LVAD. While NTproBNP has been extensively studied in ambulatory heart failure patients, and proven a useful prognostic marker, there is scarce evidence on its prognostic utility in LVAD patients. This multi-centre study aims to evaluate the association between NTproBNP and mortality in patients with a LVAD as bridge to heart transplant or destination therapy. METHODS AND RESULTS This is a two-center retrospective cohort study including 165 consecutive adults discharged after implantation of a durable continuous flow LVAD either as bridge to heart transplant, or as destination therapy between 2006 and 2020 at the Toronto General Hospital (Toronto, ON) and the Rigshospitalet (Copenhangen, Denmark). Uni- and multi-variable extended Cox proportional hazard models were used to evaluate the association between multiple measures of NTproBNP and mortality in LVAD patients. Of the 165 patients included in the analysis, 84 patients died and 76 patients were successfully bridged to heart transplant. Multi-variable analysis were adjusted for age, gender, type of cardiomyopathy, hypertension and diabetes. There was an increasing mortality risk with increasing NTproBNP values (Figure), with a significantly increased risk in patients with NTproBNP >1600 pmol/L in comparison to < 400 pmol/L (HR 4.4, CI 2.1-10.0). CONCLUSION Our multi-centre study demonstrates that in patients with a LVAD for bridge to transplantation or destination therapy, NTproBNP values exceeding 1600 pmol/L are significantly associated with increased risk of mortality. Larger studies may be useful to examine the prognostic utility of lower levels of NTproBNP and its association with mortality or heart-failure related hospitalizations. In patients with advanced heart failure, a left ventricular assist device (LVAD) offers improved survival and quality of life. NTproBNP is commonly measured during routine follow-up in patients with a LVAD. While NTproBNP has been extensively studied in ambulatory heart failure patients, and proven a useful prognostic marker, there is scarce evidence on its prognostic utility in LVAD patients. This multi-centre study aims to evaluate the association between NTproBNP and mortality in patients with a LVAD as bridge to heart transplant or destination therapy. This is a two-center retrospective cohort study including 165 consecutive adults discharged after implantation of a durable continuous flow LVAD either as bridge to heart transplant, or as destination therapy between 2006 and 2020 at the Toronto General Hospital (Toronto, ON) and the Rigshospitalet (Copenhangen, Denmark). Uni- and multi-variable extended Cox proportional hazard models were used to evaluate the association between multiple measures of NTproBNP and mortality in LVAD patients. Of the 165 patients included in the analysis, 84 patients died and 76 patients were successfully bridged to heart transplant. Multi-variable analysis were adjusted for age, gender, type of cardiomyopathy, hypertension and diabetes. There was an increasing mortality risk with increasing NTproBNP values (Figure), with a significantly increased risk in patients with NTproBNP >1600 pmol/L in comparison to < 400 pmol/L (HR 4.4, CI 2.1-10.0). Our multi-centre study demonstrates that in patients with a LVAD for bridge to transplantation or destination therapy, NTproBNP values exceeding 1600 pmol/L are significantly associated with increased risk of mortality. Larger studies may be useful to examine the prognostic utility of lower levels of NTproBNP and its association with mortality or heart-failure related hospitalizations.

Burden of multimorbidity in a Polish cohort of ambulatory and hospitalized heart failure patients from 2 large European registry programs: prognostic implications.

Introduction: Individual comorbidities have been shown to adversely affect prognosis in heart failure (HF). However, our knowledge of multimorbidity in HF and understanding of its prognostic implications still remain incomplete. Objectives: We aimed to analyze the prevalence of multimorbidity in Polish HF patients and to investigate the quantitative and qualitative impact of comorbidity burden on 12-month outcomes in that population. Patients and methods: We retrospectively analyzed data of 1765 Polish patients with ambulatory or acute (requiring hospitalization) HF from 2 multicenter observational European Society of Cardiology registries: the ESC-HF Pilot Survey (2009–2010) and ESC-HF-LT Registry (2011–2013). Results: Arterial hypertension and coronary artery disease were the most prevalent comorbidities, similarly to the entire European cohort. The great majority of HF patients had more than 1 predefined comorbidity and the most frequent number of comorbidities was 3. Importantly, in almost half of the patients, 4 or more comorbidities were reported. The best accuracy for predicting the adjusted 12-month rate of all-cause death was ensured by the model including only anemia and kidney dysfunction. The model including 4 comorbidities—anemia, kidney dysfunction, diabetes, and coronary artery disease—provided best accuracy for predicting 12-month rate of composite all-cause death or HF hospitalization. Conclusions: Multimorbidity is highly prevalent in a real-world cohort of Polish HF patients and the quantitative burden of comorbidities is related to increased mortality. In such patients, the clinical profile characterized by pathophysiological continuum of diabetes, kidney dysfunction, and anemia is particularly associated with unfavorable outcomes.

An early relook identifies high-risk trajectories in ambulatory advanced heart failure

Patients with ambulatory advanced heart failure (HF) are increasingly considered for durable mechanical circulatory support (MCS) and heart transplantation and their effective triage requires careful assessment of the clinical trajectory. REVIVAL, a prospective, observational study, enrolled 400 ambulatory advanced HF patients from 21 MCS/transplant centers in 2015-2016. Study design included a clinical re-assessment of Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profile within 120 days after enrollment. The prognostic impact of a worsening INTERMACS Profile assigned by the treating physician was assessed at 1 year after the Early Relook. Early Relook was done in 325 of 400 patients (81%), of whom 24% had a worsened INTERMACS Profile, associated with longer HF history and worse baseline INTERMACS profile, but no difference in baseline LVEF (median 0.20), 6-minute walk, quality of life, or other baseline parameters. Early worsening predicted higher rate of the combined primary endpoint of death, urgent MCS, or urgent transplant by 1 year after Early Relook, (28% vs 15%), with hazard ratio 2.2 (95% CI 1.2- 3.8; p=.006) even after adjusting for baseline INTERMACS Profile and Seattle HF Model score. Deterioration to urgent MCS occurred in 14% vs 5% (p=.006) during the year after Early Relook. Early Relook identifies worsening of INTERMACS Profile in a significant population of ambulatory advanced HF, who had worse outcomes over the subsequent year. Early reassessment of ambulatory advanced HF patients should be performed to better define the trajectory of illness and inform triage to advanced therapies.

Characteristics and outcome of ambulatory heart failure patients receiving a left ventricular assist device.

AimsDespite regularly updated guidelines, there is still a delay in referral of advanced heart failure patients to mechanical circulatory support and transplant centres. We aimed to analyse characteristics and outcome of non‐inotrope‐dependent patients implanted with a left ventricular assist device (LVAD).Methods and resultsThe ASSIST‐ICD registry collected LVAD data in 19 centres in France between February 2006 and December 2016. We used data of patients in Interagency Registry for Mechanically Assisted Circulatory Support Classes 4–7. The primary endpoint was survival analysis. Predictors of mortality were searched with multivariable analyses. A total of 303 patients (mean age 61.0 ± 9.9 years, male sex 86.8%) were included in the present analysis. Ischaemic cardiomyopathy was the leading heart failure aetiology (64%), and bridge to transplantation was the main implantation strategy (56.1%). The overall likelihood of being alive while on LVAD support or having a transplant at 1, 2, 3, and 5 years was 66%, 61.7%, 58.7%, and 55.1%, respectively. Age [hazard ratio (HR) 1.03, 95% confidence interval (CI) 1.00–1.05; P = 0.02], a concomitant procedure (HR 2.32, 95% CI 1.52–3.53; P < 0.0001), and temporary mechanical right ventricular support during LVAD implantation (HR 2.94, 95% CI 1.49–5.77; P = 0.002) were the only independent variables associated with mortality. Heart failure medications before or after LVAD implantation were not associated with survival.ConclusionAmbulatory heart failure patients displayed unsatisfactory survival rates after LVAD implantation. A better selection of patients who can benefit from LVAD may help improving outcomes.

The ‘Surprise question’ in heart failure: a prospective cohort study

ObjectiveThe Surprise Question (SQ) is a prognostic screening tool used to identify patients with limited life expectancy. We assessed the SQ’s performance predicting 1-year mortality among patients in ambulatory heart...

Prognostic value of natriuretic peptides in heart failure: systematic review and meta-analysis

Risk models, informing optimal long-term medical management, seldom use natriuretic peptides (NP) in ascertaining the absolute risk of outcomes for HF patients. Individual studies evaluating the prognostic value of NPs in HF patients have reported varying effects, arriving at best estimates requires a systematic review. We systematically summarized the best evidence regarding the prognostic value of brain natriuretic peptide (BNP) and NT-proBNP in predicting mortality and hospitalizations in ambulatory heart failure (HF) patients. We searched bibliographic databases from 2005 to 2018 and included studies evaluating the association of BNP or NT-proBNP with mortality or hospitalization using multivariable Cox proportional hazard models. We pooled hazard ratios using random-effect models, explored heterogeneity using pre-specified subgroup analyses, and evaluated the certainty of evidence using the Grading of Recommendations and Development Evaluation framework. We identified 67 eligible studies reporting on 76,178 ambulatory HF patients with a median BNP of 407pg/mL (261-574pg/mL). Moderate to high-quality evidence showed that a 100-pg/mL increase in BNP was associated with a 14% increased hazard of mortality (HR 1.14, 95% CI 1.06-1.22); a 1-log-unit increase was associated with a 51% increased hazard of mortality (HR 1.51, 95% CI 1.41-1.61) and 48% increased hazard of mortality or hospitalization (HR 1.48, 95% CI 1.29-1.69). With moderate to high certainty, we observed a 14% independent relative increase in mortality, translating to a clinically meaningful increase in absolute risk even for low-risk patients. The observed associations may help in developing more accurate risk models that incorporate NPs and accurately prognosticate HF patients.

Primary results of long-term outcomes in the MOMENTUM 3 pivotal trial and continued access protocol study phase: a study of 2200 HeartMate 3 left ventricular assist device implants.

AimThe MOMENTUM 3 pivotal trial established superiority of the HeartMate 3 (HM3) left ventricular assist device (LVAD), a fully magnetically levitated centrifugal‐flow pump, over the HeartMate II axial‐flow pump. We now evaluate HM3 LVAD outcomes in a single‐arm prospective continuous access protocol (CAP) post‐pivotal trial study.Methods and resultsWe enrolled 2200 HM3 implanted patients (515 pivotal trial and 1685 CAP patients) and compared outcomes including survival free of disabling stroke or reoperation to replace or remove a malfunctioning device (primary composite endpoint), overall survival and major adverse events at 2 years. The 2‐year primary endpoint [76.7% vs. 74.8%; adjusted hazard ratio (HR) 0.87, 95% confidence interval (CI) 0.71–1.08, P = 0.21] and overall survival (81.2% vs. 79.0%) were similar among CAP and pivotal cohorts despite sicker patients (more intra‐aortic balloon pump use and INTERMACS profile 1) in CAP who were more often intended for destination therapy. Survival was similar between the CAP and pivotal trial in transplant ineligible patients (79.1% vs. 76.7%; adjusted HR 0.89, 95% CI 0.68–1.16, P = 0.38). In a pooled analysis, the 2‐year primary endpoint was similar between INTERMACS profiles 1–2 (‘unstable’ advanced heart failure), profile 3 (‘stable’ on inotropic therapy), and profiles 4–7 (‘stable’ ambulatory advanced heart failure) (75.7% vs. 77.6% vs. 72.9%, respectively). The net burden of adverse events was lower in CAP (adjusted rate ratio 0.93, 95% CI 0.88–0.98, P = 0.006), with consequent decrease in hospitalization.ConclusionsThe primary results of accumulating HM3 LVAD experience suggest a lower adverse event burden and similar survival compared to the pivotal MOMENTUM 3 trial.

MONITORIA: The start of a new era of ambulatory heart failure monitoring? Part II - Design.

Heart failure (HF) represents a huge financial and economic burden worldwide. Some authors advocate that remote monitoring should be implemented to improve HF management, but given its increasing incidence, as well as its morbidity and mortality, a question still remains: are we monitoring it properly? There is no shortage of literature on home monitoring devices, however, most of them are designed to monitor an unsuitable array of variables and, to the best of our knowledge, there are no large randomized studies about their impact on morbidity/mortality of HF patients. Description of a novel monitoring device. As a solution, we designed MONITORIA (MOnitoring NonInvasively To Overcome mortality Rates of heart Insufficiency on Ambulatory). This is a multimodal device that will provide real time monitoring of vital, electrophysiological, hemodynamic and chemical signs, transthoracic impedance, and physical activity levels. The device is meant to perform continuous analysis and transmission of all data. Significant alterations in a patient's variable will alert the attending physician and, in case of potentially life-threatening situations, the national emergency medical system. The MONITORIA device will, also, have a function that sends shocks or functions as a pacemaker to treat certain arrhythmias/blockades. This function can be activated the very first time the patient utilizes it, based on their risk of sudden cardiac death. MONITORIA is a promising device mostly because it is included in a follow-up program that takes into account a multi-perspective feature of HF development and is based on the real world patient, adapting innovations not to the disease but rather to the patients.

MONITORIA: The start of a new era of ambulatory heart failure monitoring? Part I - Theoretical Rationale.

Heart failure (HF) is a multifactorial chronic syndrome with progressive increasing incidence causing a huge financial burden worldwide. Remote monitoring should, in theory, improve HF management, but given increasing morbidity and mortality, a question remains: are we monitoring it properly? Device-based home monitoring enables objective and continuous measurement of vital variables and non-invasive devices should be first choice for elderly patients. There is no shortage of literature on the subject, however, most studies were designed to monitor a single variable or class of variables that were not properly assembled and, to the best of our knowledge, there are no large randomized studies about their impact on HF patient management. To overcome this problem, we carefully selected the most critical possible HF decompensating factors to design MONITORIA, a non-invasive device for comprehensive HF home monitoring. MONITORIA stands for MOnitoring Non-Invasively To Overcome mortality Rates of heart Insufficiency on Ambulatory, and in this paper, which is part I of a series of three articles, we discuss the theoretical basis for its design. MONITORIA and its inherent follow-up strategy will optimize HF patient care as it is a promising device, which will essentially adapt innovation not to the disease but rather to the patients.

MONITORIA: The start of a new era of ambulatory heart failure monitoring? Part II – Design

IntroductionHeart failure (HF) represents a huge financial and economic burden worldwide. Some authors advocate that remote monitoring should be implemented to improve HF management, but given its increasing incidence, as well as its morbidity and mortality, a question still remains: are we monitoring it properly? There is no shortage of literature on home monitoring devices, however, most of them are designed to monitor an unsuitable array of variables and, to the best of our knowledge, there are no large randomized studies about their impact on morbidity/mortality of HF patients. ObjectiveDescription of a novel monitoring device. MethodsAs a solution, we designed MONITORIA (MOnitoring NonInvasively To Overcome mortality Rates of heart Insufficiency on Ambulatory). ResultsThis is a multimodal device that will provide real time monitoring of vital, electrophysiological, hemodynamic and chemical signs, transthoracic impedance, and physical activity levels. The device is meant to perform continuous analysis and transmission of all data. Significant alterations in a patient's variable will alert the attending physician and, in case of potentially life-threatening situations, the national emergency medical system. The MONITORIA device will, also, have a function that sends shocks or functions as a pacemaker to treat certain arrhythmias/blockades. This function can be activated the very first time the patient utilizes it, based on their risk of sudden cardiac death. Discussion/ConclusionsMONITORIA is a promising device mostly because it is included in a follow-up program that takes into account a multi-perspective feature of HF development and is based on the real world patient, adapting innovations not to the disease but rather to the patients.

Worsening Heart Failure Episodes Outside a Hospital Setting in Heart Failure With Preserved Ejection Fraction: The PARAGON-HF Trial

ObjectivesThis study sought to evaluate the frequency and prognostic implications of urgent heart failure (HF) visits in a large global clinical trial of HF with preserved ejection fraction (HFpEF). BackgroundEpisodes of worsening HF managed without hospitalization are common and prognostically important in HF with reduced ejection fraction (EF). The significance of these ambulatory worsening HF events in HFpEF is uncertain. MethodsPARAGON-HF (Prospective Comparison of ARNI with ARB Global Outcomes in HF with Preserved Ejection Fraction) randomly assigned 4,796 patients with HFpEF (≥45%) to treatment with sacubitril/valsartan vs. valsartan with a primary composite endpoint of total HF hospitalizations and cardiovascular death. Urgent ambulatory HF visits requiring intravenous diuretic treatment were prospectively collected and adjudicated by a blinded committee. We examined the effect of study treatment on a prespecified expanded composite of cardiovascular death and worsening HF events (including HF hospitalizations and urgent HF visits) and the effect of each type of HF event on subsequent mortality. ResultsOf 884 first worsening HF events, 66 (7.5%) were urgent HF visits. Patients whose first episode of worsening HF event was an urgent visit had similar age, comorbidities, baseline N-terminal prohormone of B-type natriuretic peptide, and Meta-Analysis Global Group in Chronic Heart Failure risk scores to those in whom the first HF event was a hospitalization (all comparisons p > 0.05). Regardless of the treatment setting, patients with a first episode of worsening HF had higher rates of subsequent death (19.2 per 100 patient-years; 95% confidence interval [CI]: 16.9 to 21.8 for HF hospitalization and 10.1 per 100 patients-years; 95% CI: 5.4 to 18.7 for urgent HF visit) compared with those who did not experience worsening HF (death rate 4.0 per 100 patient-years; 95% CI: 3.6 to 4.4). Including total urgent HF visits in the composite study endpoint added 95 total events and would have shortened the trial duration needed for event accrual. The addition of urgent HF visits in a prespecified composite endpoint reinforced the treatment efficacy of sacubitril/valsartan compared with valsartan (rate ratio 0.86; 95% CI: 0.75 to 0.99; p = 0.040). ConclusionsLike HF hospitalizations, worsening HF events treated in the ambulatory setting are prognostically important in HFpEF. Inclusion of these events in the composite primary endpoint underscores the benefit of sacubitril/valsartan compared with valsartan in PARAGON-HF. (Prospective Comparison of ARNI with ARB Global Outcomes in HF with Preserved Ejection Fraction [PARAGON-HF]; NCT01920711)

Small decreases in biventricular pacing percentages are associated with multiple metrics of worsening heart failure as measured from a cardiac resynchronization therapy defibrillator

BackgroundLower BiVentricular (BiV) pacing percentages have been associated with significantly worse survival in patients with chronic heart failure (HF). However, the pathophysiology behind this observation has not been further delineated. This analysis evaluated whether small incremental decreases in BiV pacing percentages were associated with worse measures, related to HF physiology using individual sensor trends and the HeartLogic composite index. MethodsSensor data was obtained from 900 ambulatory HF patients with implanted CRT devices. The percent of cardiac cycles with BiV pacing was assessed for periods (median = 7.3 days) between data downloads (median = 55 periods/patient). ResultsThe third heart sound (S3), respiration rate, RSBI, and night-time heart rate were significantly elevated with sub-optimal pacing (<98%), while the first heart sound (S1), thoracic impedance, and activity were significantly lower. All sensor changes were in the direction associated with worsening HF. While IN the HeartLogic alert state (threshold above an Index of 16) the odds of optimal BiV pacing (≥98%) were less than when OUT of the HeartLogic alert state for a given subject (OR: 0.655; 95% CI: 0.626–0.686; p < 0.0001). The percent BiV pacing was reduced and the HeartLogic Index was increased in the periods surrounding HFhospitalizations. ConclusionLower BiV pacing percent is associated with multiple sensor changes indicative of worsening HF, and patients in HeartLogic alert are more likely to have suboptimal BiV pacing. Collectively, these data provide strong evidence that even small decreases in BiV percent pacing can lead to worsening HF.

The impact of the coronavirus disease and Tele-Heart Failure Clinic on cardiovascular mortality and heart failure hospitalization in ambulatory patients with heart failure.

BackgroundWe sought to investigate the impact of the COVID-19 pandemic and the Tele-HF Clinic (Tele-HFC) program on cardiovascular death, heart failure (HF) rehospitalization, and heart transplantation rates in a cohort of ambulatory HF patients during and after the peak of the pandemic.MethodsUsing the HF clinic database, we compared data of patients with HF before, during, and after the peak of the pandemic (January 1 to March 17 [pre-COVID], March 17 to May 31 [peak-COVID], and June 1 to October 1 [post-COVID]). During peak-COVID, all patients were managed by Tele-HFC or hospitalization. After June 1, patients chose either a face-to-face clinic visit or a continuous tele-clinic visit.ResultsCardiovascular death and medical titration rates were similar in peak-COVID compared with all other periods. HF readmission rates were significantly lower in peak-COVID (8.7% vs. 2.5%, p<0.001) and slightly increased (3.5%) post-COVID. Heart transplant rates were substantially increased in post-COVID (4.5% vs. peak-COVID [0%], p = 0.002). After June 1, 38% of patients continued with the Tele-HFC program. Patients managed by the Tele-HFC program for <6 months were less likely to have HF with reduced ejection fraction (73% vs. 54%, p = 0.005) and stage-D HF (33% vs. 14%, p = 0.001), and more likely to achieve the target neurohormonal blockade dose (p<0.01), compared with the ≥6-month Tele-HFC group.ConclusionsHF rehospitalization and transplant rates significantly declined during the pandemic in ambulatory care of HF. However, reduction in these rates did not affect subsequent 5-month hospitalization and cardiovascular mortality in the setting of Tele-HFC program and continuum of advanced HF therapies.

CS as a Novel Biomarker for Diagnosis of Cardiac Allograft Rejection

Purpose Cardiac bridging integrator 1 (cBIN1) is a cardiomyocyte protein which regulates excitation-contraction coupling and is downregulated with adverse myocardial remodeling. The natural log of the inverse of cBIN1 plasma concentration known as CS, has been shown to be a diagnostic and prognostic marker for ambulatory heart failure patients. In this pilot study, we examined the performance of CS as a diagnostic marker of cardiac allograft rejection. Methods Out of 708 heart transplant (HT) recipients consented for the study from 2014 to 2018, 12 patients experienced advanced rejection (AMR/ACR grade ≥2) with CS level drawn at the time. Convalescent sera were drawn at least 6 months post therapy. A control group of 11 patients was matched by age, sex and time since HT. CS was measured in plasma samples by Sarcotein, Inc. Pair-wise comparison of CS among the 2 groups was performed using the Wilcoxon signed rank test. Major adverse outcomes (MACE), defined as ventricular tachycardia, cardiac allograft vasculopathy, recurrent rejection, cardiac hospitalization, and death were determined by chart review at most recent clinic visit. Results Rejection occurred at 211 (IQR 127-303) days post-HT. Patients with rejection had significantly lower CS levels compared to controls (1.92[IQR 1.57-2.33] vs 2.36[IQR 1.86-3.71] p=0.03). Following anti-rejection therapy, CS values were determined at 189 (IQR 126.8-303) days after the episode and did not differ significantly from the time of rejection. Notably, post rejection patients experienced a high rate of MACE (7/12) at 4 years of follow-up. Those who experienced MACE had a numerically higher median increase in CS values on follow-up compared to those who did not (1.04 vs 0.50). Conclusion In this pilot study, CS shows promise as a marker of cardiac allograft rejection. CS was significantly decreased by 20% in the setting of rejection compared to matched control samples. Larger studies are needed to validate our findings and determine the prognostic value of CS level changes post-therapy.

Diuretic response and effects of diuretic omission in ambulatory heart failure patients on chronic low-dose loop diuretic therapy.

To study loop diuretic response and effect of loop diuretic omission in ambulatory heart failure (HF) patients on chronic low-dose loop diuretics. Urine collections were performed on two consecutive days in 40 ambulatory HF patients with 40-80 mg furosemide (day 1 with loop diuretic; day 2 without loop diuretic). Three phases were collected each day: (i) first 6h; (ii) rest of the day; and (iii) night. On the day of loop diuretic intake, the total natriuresis was 125.9 (86.9-155.0) mmol/24 h and urine output was 1650 (1380-2025) mL/24 h. There was a clear loop diuretic response with a natriuresis of 9.4 (6.7-15.9) mmol/h and a urine output of 117 (83-167) mL/h during the first 6h, followed by a significant drop in natriuresis and urine output during the rest of the day [2.6 (1.8-4.8) mmol/h and 55 (33-71) mL/h] and night [2.2 (1.6-3.5) mmol/h and 44 (34-73) mL/h]. On day 2, after loop diuretic omission, the natriuresis and urine output remained similarly low the entire day, resulting in a 50% reduction in natriuresis [55.1 (33.5-77.7) mmol/24 h; P < 0.001] and a 31% reduction in urine output [1035 (875-1425) mL/24 h; P < 0.001] compared with the day of loop diuretic intake. Patients with HF on chronic loop diuretic treatment still have a clear diuretic response phase, while loop diuretic omission leads to a significant drop in natriuresis and urine output, arguing against routine cessation of low-dose loop diuretics.

Splanchnic Nerve Block Mediated Changes in Stressed Blood Volume in Heart Failure

ObjectivesThe authors estimated changes of stressed blood volume (SBV) induced by splanchnic nerve block (SNB) in patients with either decompensated or ambulatory heart failure with reduced ejection fraction (HFrEF). BackgroundThe splanchnic vascular capacity is a major determinant of the SBV, which in turn determines cardiac filling pressures and may be modifiable through SNB. MethodsWe analyzed data from 2 prospective, single-arm clinical studies in decompensated HFrEF (splanchnic HF-1; resting hemodynamics) and ambulatory heart failure (splanchnic HF-2; exercise hemodynamics). Patients underwent invasive hemodynamics and short-term SNB with local anesthetics. SBV was simulated using heart rate, cardiac output, central venous pressure, pulmonary capillary wedge pressure, systolic and diastolic systemic arterial and pulmonary artery pressures, and left ventricular ejection fraction. SBV is presented as ml/70 kg body weight. ResultsMean left ventricular ejection fraction was 21 ± 11%. In patients with decompensated HFrEF (n = 11), the mean estimated SBV was 3,073 ± 251 ml/70 kg. At 30 min post-SNB, the estimated SBV decreased by 10% to 2,754 ± 386 ml/70 kg (p = 0.003). In ambulatory HFrEF (n = 14) patients, the mean estimated SBV was 2,664 ± 488 ml/70 kg and increased to 3,243 ± 444 ml/70 kg (p < 0.001) at peak exercise. The resting estimated SBV was lower in ambulatory patients with HFrEF than in decompensated HFrEF (p = 0.019). In ambulatory patients with HFrEF, post-SNB, the resting estimated SBV decreased by 532 ± 264 ml/70 kg (p < 0.001). Post-SNB, with exercise, there was no decrease of estimated SBV out of proportion to baseline effects (p = 0.661). ConclusionsThe estimated SBV is higher in decompensated than in ambulatory heart failure. SNB reduced the estimated SBV in decompensated and ambulatory heart failure. The reduction in estimated SBV was maintained throughout exercise. (Splanchnic Nerve Anesthesia in Heart Failure, NCT02669407; Abdominal Nerve Blockade in Chronic Heart Failure, NCT03453151)

Prognostic value of blood pressure in ambulatory heart failure: a meta-analysis and systematic review. Ambulatory blood pressure predicts heart failure prognosis.

Previous primary studies have explored the association between blood pressure (BP) and mortality in ambulatory heart failure (HF) patients reporting varying and contrasting associations. The aim is to determine the pooled BP prognostic value and explore potential reasons for between-study inconsistency. We searched Medline, Cochrane, EMBASE and CINAHL from January 2005 to October 2018 for studies with ≥50 events (mortality and/or hospitalization) and included BP in a multivariable model in ambulatory HF patients. We pooled hazard ratios (random effects model) for systolic BP (SBP) or diastolic BP (DBP) effect on mortality and/or hospitalization risk. We used a priori defined sub-group analyses to explore heterogeneity and GRADE approach to assess the certainty of the evidence. Seventy-one eligible articles (239,467 screened) at low to moderate risk of bias included 235,752 participants. Higher SBP was associated with reduced all-cause mortality (HR 0.93, 95%CI 0.91-0.95, I2=87.13%, moderate certainty), all-cause hospitalization events (HR 0.91, 95%CI 0.88-0.93, I2=44.4%, high certainty) and their composite endpoint (HR 0.93 per 10 mmHg, 95%CI 0.91-0.94, I2=86.3%, high certainty). DBP did not demonstrate a statistically significant effect for all outcomes. The association strength was significantly weaker in studies following patients with either LVEF>40%, higher average SBP (>130mmHg), increasing age and diabetes. All other a priori subgroup hypotheses did not explain between study differences. Higher ambulatory SBP is associated with reduced risk of all-cause mortality and hospitalization. Patients with lower BP and reduced LVEF are in a high-risk group of developing adverse events with moderate certainty of evidence.

Evaluation of the prescribing practice of guideline-directed medical therapy among ambulatory chronic heart failure patients

BackgroundStudies have demonstrated that heart failure (HF) patients who receive direct pharmacist input as part of multidisciplinary care have better clinical outcomes. This study evaluated/compared the difference in prescribing practices of guideline-directed medical therapy (GDMT) for chronic HF patients between two multidisciplinary clinics—with and without the direct involvement of a pharmacist.MethodsA retrospective audit of chronic HF patients, presenting to two multidisciplinary outpatient clinics between March 2005 and January 2017, was performed; a Multidisciplinary Ambulatory Consulting Service (MACS) with an integrated pharmacist model of care and a General Cardiology Heart Failure Service (GCHFS) clinic, without the active involvement of a pharmacist.ResultsMACS clinic patients were significantly older (80 vs. 73 years, p < .001), more likely to be female (p < .001), and had significantly higher systolic (123 vs. 112 mmHg, p < .001) and diastolic (67 vs. 60 mmHg, p < .05) blood pressures compared to the GCHF clinic patients. Moreover, the MACS clinic patients showed more polypharmacy and higher prevalence of multiple comorbidities. Both clinics had similar prescribing rates of GDMT and achieved maximal tolerated doses of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) in HFrEF. However, HFpEF patients in the MACS clinic were significantly more likely to be prescribed ACEIs/ARBs (70.5% vs. 56.2%, p = 0.0314) than the GCHFS patients. Patients with both HFrEF and HFpEF (MACS clinic) were significantly less likely to be prescribed β-blockers and mineralocorticoid receptor antagonists. Use of digoxin in chronic atrial fibrillation (AF) in MACS clinic was significantly higher in HFrEF patients (82.5% vs. 58.5%, p = 0.004), but the number of people anticoagulated in presence of AF (27.1% vs. 48.0%, p = 0.002) and prescribed diuretics (84.0% vs. 94.5%, p = 0.022) were significantly lower in HFpEF patients attending the MACS clinic. Age, heart rate, systolic blood pressure (SBP), anemia, chronic renal failure, and other comorbidities were the main significant predictors of utilization of GDMT in a multivariate binary logistic regression.ConclusionsLower prescription rates of some medications in the pharmacist-involved multidisciplinary team were found. Careful consideration of demographic and clinical characteristics, contraindications for use of medications, polypharmacy, and underlying comorbidities is necessary to achieve best practice.

Sex-Based Differences in Outpatient Specialist Referral Patterns of Heart Failure Patients: A Scoping Review

Heart failure (HF) is a highly prevalent disease, causing significant morbidity and mortality in both men and women. Current guidelines recommend that patients diagnosed with HF during hospitalization be referred to an outpatient HF clinic within two weeks of discharge. We conducted a scoping review to identify potential sex differences in the referral of these patients to ambulatory HF clinics.

Beyond the stethoscope: managing ambulatory heart failure during the COVID-19 pandemic.

There have been nearly 70 million cases of COVID‐19 worldwide, with over 1.5 million deaths at the time of this publication. This global pandemic has mandated dramatic changes in healthcare delivery with a particular focus on social distancing in order to reduce viral transmission. Heart failure patients are among the highest utilizers of health care and are at increased risk for COVID‐related vulnerabilities. Effectively managing this complex and resource‐intensive patient population from a distance presents new and unique challenges. Here, we review relevant data on telemedicine and remote monitoring strategies for heart failure patients and provide a framework to help providers treat this population during the COVID‐19 pandemic. This includes (i) dedicated pre‐visit contact and planning (i.e. confirm clinical appropriateness, presence of compatible technology, and patient comfort); (ii) utilization of virtual clinic visits (use of telehealth platforms, a video‐assisted exam, self‐reported vital signs, and weights); and (iii) use of existing remote heart failure monitoring sensors when applicable (CardioMEMS, Optivol, and HeartLogic). While telemedicine and remote monitoring strategies are not new, these technologies are emerging as an important tool for the effective management of heart failure patients during the COVID‐19 pandemic. In general, these strategies appear to be safe; however, additional data will be needed to determine their effectiveness with respect to both process and outcomes measures.