Long term safety and outcomes after atrial shunting for heart failure with preserved or mildly reduced ejection fraction: 5-year and 3-year follow-up in the REDUCE LAP-HF I and II trials.

BACKGROUND: There is a little evidence regarding long-term safety and efficacy for atrial shunt devices in heart failure (HF). METHODS: The REDUCE LAP-HF I (n=44) and II (n=621) trials (RCT-I and -II) were multicenter, randomized, sham-controlled trials of patients with HF and ejection fraction >40%. Outcome data were analyzed from RCT-I, a mechanistic trial with 5-year follow-up, and RCT-II, a pivotal trial identifying a responder group (n=313) defined by exercise PVR <1.74 WU and no cardiac rhythm management device with 3-year follow-up. RESULTS: At 5 years in RCT I, there were no differences in cardiovascular (CV) mortality, HF events, embolic stroke, or new-onset atrial fibrillation between groups. After 3 years in RCT II, there was no difference in the primary outcome (hierarchical composite of CV mortality, stroke, HF events, and KCCQ) between shunt and sham in the overall trial. Compared to sham, those with responder characteristics in RCT-II had a better outcome with shunt (win ratio 1.6 [95% CI 1.2-2.2], P=0.006; 44% reduction in HF events [shunt 9 vs. control 16 per 100 patient-years], P=0.005; and greater improvement in KCCQ overall summary score [+17.9±20.0 vs. +7.6±20.4], P<0.001), while non-responders had significantly more HF events. Shunt treatment at 3 years was associated with a higher rate of ischemic stroke (3.2% vs. 0%, 95% CI 2% - 6.1%, p=0.032) and lower incidence of worsening kidney dysfunction (10.7% vs. 19.3%, p=0.041). CONCLUSIONS: With up to 5 years of follow up, adverse events were low in patients receiving atrial shunts. In the responder group, atrial shunt treatment was associated with a significantly lower HF event rate and improved KCCQ compared to sham through 3 years of follow-up. CLINICALTRIALS: gov registration: NCT02600234, NCT03088033.

Standardization of quantitative PCR (qPCR) method to detect the level of parasitaemia in Babesia gibsoni infected dogs.

The present investigation aimed to quantitatively assess the level of parasitemia in dogs using qPCR.The dogs selected for this study were infected with the haemoprotozoan parasite Babesia gibsoni. In the study, dogs diagnosed with babesiosis were divided into two groups (n = 12) and subjected to distinct treatment strategies. The first group received clindamycin-metronidazole-doxycycline (CMD) therapy, while the second group was treated with a combination of buparvaquone-azithromycin (BPV-AZM). The level of parasitemia in the infected dogs was determined using an absolute quantification-based qPCR method. This assessment was conducted both prior to initiating the treatment and on the 10th day following the commencement of the treatment protocols. On the tenth day after the initiation of treatment, the CMD group exhibited a lower level of parasitemia in comparison to the BPV-AZM group. In the CMD treated groups, the mean parasitemia decreased from 4.9E + 06 to 3.4E + 06, indicating a reduction in parasitic load. Conversely, in the BPV-AZM treatment groups, the mean parasitemia increased from 1.62E + 06 to 2.87E + 06, suggesting an increase in parasitic load. On the 10th day, the CMD-treated group demonstrated a statistically significant decline in the level of parasitemia, with a P-value of ≤0.001. This indicates a strong and significant reduction in parasitic load following the CMD treatment. Therefore, the absolute quantification-based qPCR method could effectively assess the initial treatment response by measuring the level of parasitemia.

Effect of Preoperative Mitral Regurgitation on LVAD Outcomes in Patients with Elevated Pulmonary Vascular Resistance.

PURPOSE: In patients with end-stage heart failure who undergo left ventricular assist device (LVAD) implantation, higher pulmonary vascular resistance (PVR) is associated with higher right heart failure rates and ineligibility for heart transplant. Concomitant mitral regurgitation (MR) could potentially worsen pulmonary hemodynamics and lead to worse outcomes; however, its effects in this patient population have not been specifically examined. METHODS: Using an institutional database spanning November 2003 to August 2017, we retrospectively identified patients with elevated PVR who underwent LVAD implantation. Patients were stratified by concurrent MR: moderate/severe (PVR + MR) vs. mild/none (PVR - MR). Cumulative incidence functions and Fine-Gray competing risk regression were performed to assess the effect of MR on heart transplant rates and overall survival during index LVAD support. RESULTS: Of 644 LVAD recipients, 232 (171 HeartMate II, 59 HeartWare, 2 HeartMate III) had baseline PVR > 3 Woods units; of these, 124 (53%) were INTERMACS 1-2, and 133 (57%) had moderate/severe MR (≥ 3 +). Patients with PVR + MR had larger a baseline left ventricular end-diastolic diameter than patients with PVR - MR (87.9 ± 38.2 mm vs. 75.9 ± 38.0 mm; P = 0.02). Median clinical follow-up was 18.8 months (interquartile range: 4.7-36.4 months). Moderate/severe MR was associated with lower mortality rates during index LVAD support (adjusted hazard ratio 0.64, 95% CI 0.41-0.98; P = 0.045) and higher heart transplant rates (adjusted odds ratio 2.86, 95% CI 1.31-6.25; P = 0.009). No differences in stroke, gastrointestinal bleeding, or right heart failure rates were observed. CONCLUSIONS: Among LVAD recipients with elevated preoperative PVR, those with moderate/severe MR had better overall survival and higher transplant rates than those with mild/no MR. These hypothesis-generating findings could be explained by incremental LVAD benefits resulting from reduction of MR and better LV unloading in a subset of patients with larger ventricles at baseline. In patients with preoperative elevated PVR, MR severity may be a prognostic sign that can inform patient selection for end-stage heart failure therapy.

Mortality in Recipients of Durable Left Ventricular Assist Devices Undergoing Ventricular Tachycardia Ablation.

BACKGROUND: Left ventricular assist device (LVAD) recipients have a higher incidence of ventricular tachycardia (VT). However, the role of VT ablation in this population is not well-established. OBJECTIVES: This single-center retrospective cohort study sought to examine the impact of post-LVAD implant VT ablation on survival. METHODS: This retrospective study examined a cohort of patients that underwent LVAD implantation at Baylor St. Luke's Medical Center and Texas Heart Institute between January 2011 and January 2021. All-cause estimated mortality was compared across LVAD recipients based on the incidence of VT, timing of VT onset, and the occurrence and timing of VT ablation utilizing Kaplan-Meier survival analysis and Cox proportional hazards models. RESULTS: Post-implant VT occurred in 53% of 575 LVAD recipients. Higher mortality was seen among patients with post-implant VT within a year of implantation (HR: 1.62 [95% CI: 1.15-2.27]). Among this cohort, patients who were treated with a catheter ablation had superior survival compared with patients treated with medical therapy alone for the 45 months following VT onset (HR: 0.48 [95% CI: 0.26-0.89]). Moreover, performance of an ablation in this population aligned mortality rates with those who did not experience post-implant VT (HR: 1.18 [95% CI: 0.71-1.98]). CONCLUSIONS: VT occurrence within 1 year of LVAD implantation was associated with worse survival. However, performance of VT ablation in this population was correlated with improved survival compared with medical management alone. Among patients with refractory VT, catheter ablation aligned survival with other LVAD participants without post-implant VT. Catheter ablation of VT is associated with improved survival in LVAD recipients, but further prospective randomized studies are needed to compare VT ablation to medical management in LVAD recipients.

Considerations in the Diagnosis and Management of Pulmonary Hypertension Associated With Left Heart Disease.

Pulmonary hypertension associated with left heart disease (PH-LHD) remains the most common cause of pulmonary hypertension globally. Etiologies include heart failure with reduced and preserved ejection fraction and left-sided valvular heart diseases. Despite the increasing prevalence of PH-LHD, there remains a paucity of knowledge about the hemodynamic definition, diagnosis, treatment modalities, and prognosis among clinicians. Moreover, clinical trials have produced mixed results on the usefulness of pulmonary vasodilator therapies for PH-LHD. In this expert review, we have outlined the critical role of meticulous hemodynamic evaluation and provocative testing for cases of diagnostic uncertainty. Therapeutic strategies-pharmacologic, device-based, and surgical therapies used for managing PH-LHD-are also outlined. PH-LHD in advanced heart failure, and the role of mechanical circulatory support in PH-LHD is briefly explored. An in-depth understanding of PH-LHD by all clinicians is needed for improved recognition and outcomes among patients with PH-LHD.

Predictors and Impact of Prolonged Vasoplegia After Continuous-Flow Left Ventricular Assist Device Implantation.

Background: Vasoplegia after cardiac surgery is associated with adverse outcomes. However, the clinical effects of vasoplegia and the significance of its duration after continuous-flow left ventricular assist device (CF-LVAD) implantation are less known. Objectives: This study aimed to identify predictors of and outcomes from transient vs prolonged vasoplegia after CF-LVAD implantation. Methods: The study was a retrospective review of consecutive patients who underwent CF-LVAD implantation between January 1, 2005, and December 31, 2017. Vasoplegia was defined as the presence of all of the following: mean arterial pressure ≤65 mm Hg, vasopressor (epinephrine, norepinephrine, vasopressin, or dopamine) use for >6 hours within the first 24 hours postoperatively, cardiac index ≥2.2 L/min/m2 and systemic vascular resistance <800 dyne/s/cm5, and vasodilatory shock not attributable to other causes. Prolonged vasoplegia was defined as that lasting 12 to 24 hours; transient vasoplegia was that lasting 6 to <12 hours. Patient characteristics, outcomes, and risk factors were analyzed. Results: Of the 600 patients who underwent CF-LVAD implantation during the study period, 182 (30.3%) developed vasoplegia. Mean patient age was similar between the vasoplegia and no-vasoplegia groups. Prolonged vasoplegia (n = 78; 13.0%), compared with transient vasoplegia (n = 104; 17.3%), was associated with greater 30-day mortality (16.7% vs 5.8%; P = 0.02). Risk factors for prolonged vasoplegia included preoperative dialysis and elevated body mass index. Conclusions: Compared with vasoplegia overall, prolonged vasoplegia was associated with worse survival after CF-LVAD implantation. Treatment to avoid or minimize progression to prolonged vasoplegia may be warranted.

Sex Disparities in Left Ventricular Assist Device Implantation: Delayed Presentation and Worse Right Heart Failure.

We explored whether women undergo continuous-flow left ventricular assist device (CF-LVAD) implantation in later stages of heart failure (HF) than men, evidenced by worse preoperative right HF (RHF). We also compared two propensity models with and without preoperative RHF to assess its effect on outcomes. INTERMACS was queried from July 2008 to December 2017. Propensity model 1 matched men and women on age ≥50 years, HF etiology, body surface area, INTERMACS class, comorbidities, device strategy, temporary mechanical circulatory support, and device type. Model 2 included these variables plus LV end-diastolic diameter, right atrial pressure/pulmonary capillary wedge pressure, pulmonary artery pulsatility index, and right ventricular ejection fraction. The primary outcome was all-cause mortality. Secondary outcomes comprise RHF, rehospitalization, renal dysfunction, stroke, and device malfunction. In model 1, characteristics were comparable between 3,195 women and 3,195 men, except women more often had preoperative RHF and postoperative right VAD support and had worse 1 year and overall survival. In model 2, after propensity matching for additional risk factors for preoperative RHF, 1,119 women and 1,119 men had comparable post-LVAD implant RVAD use and survival. These findings suggest that women present more often with biventricular failure and after implantation have higher RHF and mortality rates.

Combined Heart Kidney Transplantation Versus Heart Transplant in Patients with Renal Failure: Contemporary Insights and Future Perspectives.

PURPOSE OF REVIEW: In this review, we aim to outline the criteria regarding the evaluation of patients with chronic renal disease (CKD) awaiting heart transplantation and discuss the outcomes of combined heart/kidney transplantation. Herein, we also review pathophysiology and risk factors that predispose to chronic kidney disease (CKD) and acute kidney injury (AKI) in patients with HF and after OHT. RECENT FINDINGS: In patients with end-stage systolic heart failure (HF) and an estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2, orthotopic heart transplantation (OHT) alone is a relative contraindication, with a consensus that these patients are better served with heart-kidney transplant (HKT). However, there is significant variation between institutions regarding timing and indication for heart/kidney transplantation, with little data available to predict post-transplant outcomes. A Scientific Statement from American Heart Association was published detailing the indications, evaluation, and outcomes for Heart-Kidney Transplantation, and noted a steady rise in the incidence of heart/kidney dual organ transplants. Recently, the Organ Procurement and Transplantation Network (OPTN) Multi-Organ Transplantation Committee implemented a safety net policy for heart transplant recipients who do need meet criteria for simultaneous heart-kidney transplant in 2023 but with a likely need for sequential kidney transplantation. Optimization of organ distribution and patient outcomes after cardiac transplantation requires appropriate recipient selection. This review also outlines the criteria regarding the evaluation of patients with CKD awaiting heart transplantation and outcomes of combined HKT.

Clinical Predictors and Outcomes After Left Ventricular Assist Device Implantation and Tracheostomy.

BACKGROUND: Postoperative respiratory failure is a major complication that affects up to 10% of patients who undergo cardiac surgery and has a high in-hospital mortality rate. Few studies have investigated whether patients who require tracheostomy for postoperative respiratory failure after continuous-flow left ventricular assist device (CF-LVAD) implantation have worse survival outcomes than patients who do not. OBJECTIVE: To identify risk factors for respiratory failure necessitating tracheostomy in CF-LVAD recipients and to compare survival outcomes between those who did and did not require tracheostomy. METHODS: Consecutive patients who underwent primary CF-LVAD placement at a single institution between August 1, 2002, and December 31, 2019, were retrospectively reviewed. Propensity score matching accounted for baseline differences between the tracheostomy and nontracheostomy groups. Multivariate logistic regression was used to identify tracheostomy risk factors and 90-day survival; Kaplan-Meier analysis was used to assess midterm survival. RESULTS: During the study period, 664 patients received a CF-LVAD; 106 (16.0%) underwent tracheostomy for respiratory failure. Propensity score matching produced 103 matched tracheostomy-nontracheostomy pairs. Patients who underwent tracheostomy were older (mean [SD] age, 57.9 [12.3] vs 54.6 [13.9] years; P = .02) and more likely to need preoperative mechanical circulatory support (61.3% vs 47.8%; P = .01) and preoperative intubation (27.4% vs 8.8%; P < .001); serum creatinine was higher in the tracheostomy group (mean [SD], 1.7 [1.0] vs 1.4 [0.6] mg/dL; P < .001), correlating with tracheostomy need (odds ratio, 1.76; 95% CI, 1.21-2.56; P = .003). Both before and after propensity matching, 30-day, 60-day, 90-day, and 1-year survival were worse in patients who underwent tracheostomy. Median follow-up was 0.8 years (range, 0.0-11.2 years). Three-year Kaplan-Meier survival was significantly worse for the tracheostomy group before (22.0% vs 61.0%; P < .001) and after (22.4% vs 48.3%; P < .001) matching. CONCLUSION: Given the substantially increased probability of death in patients who develop respiratory failure and need tracheostomy, those at high risk for respiratory failure should be carefully considered for CF-LVAD implantation. Comprehensive management to decrease respiratory failure before and after surgery is critical.

Atrial Fibrillation Burden and Atrial Shunt Therapy in Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Atrial fibrillation (AF) is a common comorbidity in patients with heart failure with preserved ejection fraction (HFpEF) and in heart failure with mildly reduced ejection fraction (HFmrEF). OBJECTIVES: This study sought to describe AF burden and its clinical impact among individuals with HFpEF and HFmrEF who participated in a randomized clinical trial of atrial shunt therapy (REDUCE LAP-HF II [A Study to Evaluate the Corvia Medical, Inc IASD System II to Reduce Elevated Left Atrial Pressure in Patients with Heart Failure]) and to evaluate the effect of atrial shunt therapy on AF burden. METHODS: Study investigators characterized AF burden among patients in the REDUCE LAP-HF II trial by using ambulatory cardiac patch monitoring at baseline (median patch wear time, 6 days) and over a 12-month follow-up (median patch wear time, 125 days). The investigators determined the association of baseline AF burden with long-term clinical events and examined the effect of atrial shunt therapy on AF burden over time. RESULTS: Among 367 patients with cardiac monitoring data at baseline and follow-up, 194 (53%) had a history of AF or atrial flutter (AFL), and median baseline AF burden was 0.012% (IQR: 0%-1.3%). After multivariable adjustment, baseline AF burden ≥0.012% was significantly associated with heart failure (HF) events (HR: 2.00; 95% CI: 1.17-3.44; P = 0.01) both with and without a history of AF or AFL (P for interaction = 0.68). Adjustment for left atrial reservoir strain attenuated the baseline AF burden-HF event association (HR: 1.71; 95% CI: 0.93-3.14; P = 0.08). Of the 367 patients, 141 (38%) had patch-detected AF during follow-up without a history of AF or AFL. Atrial shunt therapy did not change AF incidence or burden during follow-up. CONCLUSIONS: In HFpEF and HFmrEF, nearly 40% of patients have subclinical AF by 1 year. Baseline AF burden, even at low levels, is associated with HF events. Atrial shunt therapy does not affect AF incidence or burden. (A Study to Evaluate the Corvia Medical, Inc IASD System II to Reduce Elevated Left Atrial Pressure in Patients with Heart Failure [REDUCE LAP-HF II]; NCT03088033).

Broadening Heart Failure Care Beyond Cardiology: Challenges and Successes Within the Landscape of Multidisciplinary Heart Failure Care.

PURPOSE OF REVIEW: Heart failure (HF) is a growing public health concern that impairs the quality of life and is associated with significant mortality. As the prevalence of heart failure increases, multidisciplinary care is essential to provide comprehensive care to individuals. RECENT FINDINGS: The challenges of implementing an effective multidisciplinary care team can be daunting. Effective multidisciplinary care begins at the initial diagnosis of heart failure. The transition of care from the inpatient to the outpatient setting is critically important. The use of home visits, case management, and multidisciplinary clinics has been shown to decrease mortality and heart failure hospitalizations, and major society guidelines endorse multidisciplinary care for heart failure patients. Expanding heart failure care beyond cardiology entails incorporating primary care, advanced practice providers, and other disciplines. Patient education and self-management are fundamental to multidisciplinary care, as is a holistic approach to effectively address comorbid conditions. Ongoing challenges include navigating social disparities within heart failure care and limiting the economic burden of the disease.

Continuous-Flow Ventricular Assist Device Support in Adult Congenital Heart Disease: A 15-Year, Multicenter Experience of Temporary and Durable Support.

Heart failure (HF) is common in adult congenital heart disease (ACHD) patients; however, use of continuous-flow ventricular assist devices (CF-VADs) remains rare. We reviewed outcomes of patients with congenital heart disease greater than or equal to 18 years of age at the time of CF-VAD implant at the affiliated pediatric and adult institutions between 2006 and 2020. In total, 18 ACHD patients (15 with great anatomical complexity) received 21 CF-VADs. Six patients (median age 34 years) received seven percutaneous CF-VADs with a median duration of support of 20 days (3-44 days) with all patients survived to hospital discharge and two patients were bridged to durable CF-VADs. Fourteen patients (median age 38 years) received durable CF-VADs. Thirteen patients (93%) survived to hospital discharge and the median duration of support was 25.8 months (6.4-52.1 months). Estimated survival on durable CF-VAD at 1, 3, and 5 years was 84%, 72%, and 36%, respectively. Three patients were successfully bridged to transplantation. Device-related complications include cerebrovascular accident (n = 5), driveline infection (n = 3), device infection requiring chronic antibiotic therapy (n = 4), gastrointestinal bleeding (n = 6), and presumed pump thrombosis (n = 5). These results show percutaneous and durable CF-VADs can support ACHD patients with advanced HF.

Neprilysin Inhibitors in Heart Failure: The Science, Mechanism of Action, Clinical Studies, and Unanswered Questions.

This article provides a contemporary review and a new perspective on the role of neprilysin inhibition in heart failure (HF) in the context of recent clinical trials and addresses potential mechanisms and unanswered questions in certain HF patient populations. Neprilysin is an endopeptidase that cleaves a variety of peptides such as natriuretic peptides, bradykinin, adrenomedullin, substance P, angiotensin I and II, and endothelin. It has a broad role in cardiovascular, renal, pulmonary, gastrointestinal, endocrine, and neurologic functions. The combined angiotensin receptor and neprilysin inhibitor (ARNi) has been developed with an intent to increase vasodilatory natriuretic peptides and prevent counterregulatory activation of the angiotensin system. ARNi therapy is very effective in reducing the risks of death and hospitalization for HF in patients with HF and New York Heart Association functional class II to III symptoms, but studies failed to show any benefits with ARNi when compared with angiotensin-converting enzyme inhibitors or angiotensin receptor blocker in patients with advanced HF with reduced ejection fraction or in patients following myocardial infarction with left ventricular dysfunction but without HF. These raise the questions about whether the enzymatic breakdown of natriuretic peptides may not be a very effective solution in advanced HF patients when there is downstream blunting of the response to natriuretic peptides or among post-myocardial infarction patients in the absence of HF when there may not be a need for increased natriuretic peptide availability. Furthermore, there is a need for additional studies to determine the long-term effects of ARNi on albuminuria, obesity, glycemic control and lipid profile, blood pressure, and cognitive function in patients with HF.