An ISHLT consensus statement on strategies to prevent and manage hemocompatibility related adverse events in patients with a durable, continuous-flow ventricular assist device.

Life expectancy of patients with a durable, continuous-flow left ventricular assist device (CF-LVAD) continues to increase. Despite significant improvements in the delivery of care for patients with these devices, hemocompatability-related adverse events (HRAEs) are still a concern and contribute to significant morbility and mortality when they occur. As such, dissemination of current best evidence and practices is of critical importance. This ISHLT Consensus Statement is a summative assessment of the current literature on prevention and management of HRAEs through optimal management of oral anticoagulant and antiplatelet medications, parenteral anticoagulant medications, management of patients at high risk for HRAEs and those experiencing thrombotic or bleeding events, and device management outside of antithrombotic medications. This document is intended to assist clinicians caring for patients with a CF-LVAD provide the best care possible with respect to prevention and management of these events.

State of the art on angiotensin-neprilysin inhibitors.

Angiotensin receptor neprilysin inhibitor (ARNI) decreases renin-angiotensin-aldosterone system (RAAS) and sympathetic nervous systems (SNS) activity promoting vasodilation, decreasing myocardial hypertrophy and fibrosis. Beyond the SNS, RAAS and natriuretic peptide systems, ARNI results in increased circulatory and myocardial nitric oxide levels activating cGMP and protein kinase G, which reduces oxidative stress, myocyte hypertrophy, cell death and has anti-thrombotic effects. ARNIs have a class I indication by heart failure (HF) guidelines in HFrEF patients with NYHA class II to III symptoms. Beyond HFrEF, the use of ARNIs has also been expanded to other clinical settings including HF with preserved ejection fraction (EF, HFpEF), acute HF, advanced HF, hypertension, arrhythmias and chronic kidney disease. This paper reviews the clinical benefits of ARNIs in both HF and the aforementioned cardiovascular conditions. We also discuss the combined use of ARNI with SGLT2i and their potential synergistic benefits on cardiovascular outcomes.

Management of hypertension in heart transplant recipients: an ongoing conundrum.

PURPOSE OF REVIEW: Hypertension remains one of the most common clinical problems leading to significant posttransplant complications. This study reviews the pathophysiology of hypertension in the postcardiac transplant phase and provides an update on currently available antihypertensive therapies for heart transplant patients. RECENT FINDINGS: The true prevalence of hypertension in the heart transplant population remains unknown. Effective blood pressure (BP) control is key to prevent left ventricular remodeling, diastolic dysfunction and stroke. Calcium channel blockers (CCBs) are the most commonly and preferred agents in the early posttransplant phase and may have renal protective effects. Angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs) can all be used as second line antihypertensive agents and may have a role in preventing other long-term complications such as calcineurin-inhibitor induced nephropathy. Although more data are needed, sodium-glucose co-transporter 2 inhibitors (SGLT2i) appeared to be well tolerated and could be considered especially in the presence of type diabetes and chronic kidney disease. Conversely, angiotensin receptor-neprilysin inhibition (ARNI) have not been studied in the heart transplant population therefore cannot be recommended at this time. SUMMARY: Hypertension is very common after heart transplant. Early steroid wean and traditional risk factor modification play an important part in the management of post-heart transplant hypertension. CCB, ACEI, ARB are the preferred antihypertensive agents to improve postcardiac transplant complications. Novel therapies such as SGLT2i appear well tolerated and may have benefits in both BP and glycemic control in heart transplant; however, larger trials are needed.

Torsemide vs Furosemide Among Patients With New-Onset vs Worsening Chronic Heart Failure: A Substudy of the TRANSFORM-HF Randomized Clinical Trial.

Importance: Differences in clinical profiles, outcomes, and diuretic treatment effects may exist between patients with de novo heart failure (HF) and worsening chronic HF (WHF). Objectives: To compare clinical characteristics and treatment outcomes of torsemide vs furosemide in patients hospitalized with de novo HF vs WHF. Design, Setting, and Participants: All patients with a documented ejection fraction who were randomized in the Torsemide Comparison With Furosemide for Management of Heart Failure (TRANSFORM-HF) trial, conducted from June 18 through March 2022, were included in this post hoc analysis. Study data were analyzed March to May 2023. Exposure: Patients were categorized by HF type and further divided by loop diuretic strategy. Main Outcomes and Measures: End points included all-cause mortality and hospitalization outcomes over 12 months, as well as change from baseline in the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS). Results: Among 2858 patients (mean [SD] age, 64.5 [14.0] years; 1803 male [63.1%]), 838 patients (29.3%) had de novo HF, and 2020 patients (70.7%) had WHF. Patients with de novo HF were younger (mean [SD] age, 60.6 [14.5] years vs 66.1 [13.5] years), had a higher glomerular filtration rate (mean [SD], 68.6 [24.9] vs 57.0 [24.0]), lower levels of natriuretic peptides (median [IQR], brain-type natriuretic peptide, 855.0 [423.0-1555.0] pg/mL vs 1022.0 [500.0-1927.0] pg/mL), and tended to be discharged on lower doses of loop diuretic (mean [SD], 50.3 [46.2] mg vs 63.8 [52.4] mg). De novo HF was associated with lower all-cause mortality at 12 months (de novo, 65 of 838 [9.1%] vs WHF, 408 of 2020 [25.4%]; adjusted hazard ratio [aHR], 0.50; 95% CI, 0.38-0.66; P < .001). Similarly, lower all-cause first rehospitalization at 12 months and greater improvement from baseline in KCCQ-CSS at 12 months were noted among patients with de novo HF (median [IQR]: de novo, 29.94 [27.35-32.54] vs WHF, 23.68 [21.62-25.74]; adjusted estimated difference in means: 6.26; 95% CI, 3.72-8.81; P < .001). There was no significant difference in mortality with torsemide vs furosemide in either de novo (No. of events [rate per 100 patient-years]: torsemide, 27 [7.4%] vs furosemide, 38 [10.9%]; aHR, 0.70; 95% CI, 0.40-1.14; P = .15) or WHF (torsemide 212 [26.8%] vs furosemide, 196 [24.0%]; aHR, 1.08; 95% CI, 0.89-1.32; P = .42; P for interaction = .10), In addition, no significant differences in hospitalizations, first all-cause hospitalization, or total hospitalizations at 12 months were noted with a strategy of torsemide vs furosemide in either de novo HF or WHF. Conclusions and Relevance: Among patients discharged after hospitalization for HF, de novo HF was associated with better clinical and patient-reported outcomes when compared with WHF. Regardless of HF type, there was no significant difference between torsemide and furosemide with respect to 12-month clinical or patient-reported outcomes.

Outcomes of Patients With Left Ventricular Assist Devices Requiring Intermittent Hemodialysis: Single-Center Cohort, Systematic Review, and Individual-Participant Data Meta-Analysis.

Patients with left ventricular assist devices (LVADs) who require intermittent hemodialysis (iHD) are considered to have a poor prognosis despite a paucity of supportive evidence, mostly from small single-center cohorts and extrapolations from studies of patients who received continuous renal replacement therapy but no iHD. We conducted a systematic review and individual-participant-data meta-analysis of the literature including our single-center cohort to examine the outcomes of patients initiated on iHD following LVAD implantation. Sixty-four patients from 5 cohorts met selection criteria (age 57.5 [46-64.5] years, 87% HeartMate II, mostly bridge to transplantation). Follow-up after iHD initiation was 87.5 (38.5-269.5) days, although it was considerably longer in our center than in other cohorts (601.5 [93-1559] days vs 65 [26-180] days, P = 0.0007). The estimated median survival was 308 (76-912.5) days and varied significantly among cohorts, ranging from 60 (57-65) to 838 (103-1872) days (P = 0.0096). Twelve (18.8%) patients achieved either heart transplantation (HT) or remission during follow-up. Patients who received HT had an 8-fold longer estimated median survival (1972 [799-1972] days vs 244 [64-838] days, P = 0.0112). Being from a more recent cohort was associated with better 1-year survival. Renal recovery occurred in eight patients (13.1%) at 30 days and its cumulative incidence increased to 73% (27/37 patients with available data) at 1 year. Most patients initiated on iHD after LVAD experienced renal recovery within the first year after implantation. Improved survival was observed for patients who received HT and in those from more recent cohorts. Some patients were able to survive on LVAD and iHD support for several years.

Hemodynamic-Guided Heart Failure Management in Patients With Either Prior HF Hospitalization or Elevated Natriuretic Peptides.

BACKGROUND: In patients with symptomatic heart failure (HF) and previous heart failure hospitalization (HFH), hemodynamic-guided HF management using a wireless pulmonary artery pressure (PAP) sensor reduces HFH, but it is unclear whether these benefits extend to patients who have not been recently hospitalized but remain at risk because of elevated natriuretic peptides (NPs). OBJECTIVES: This study assessed the efficacy and safety of hemodynamic-guided HF management in patients with elevated NPs but no recent HFH. METHODS: In the GUIDE-HF (Hemodynamic-Guided Management of Heart Failure) trial, 1,000 patients with New York Heart Association (NYHA) functional class II to IV HF and either previous HFH or elevated NP levels were randomly assigned to hemodynamic-guided HF management or usual care. The authors evaluated the primary study composite of all-cause mortality and total HF events at 12 months according to treatment assignment and enrollment stratum (HFH vs elevated NPs) by using Cox proportional hazards models. RESULTS: Of 999 evaluable patients, 557 were enrolled on the basis of a previous HFH and 442 on the basis of elevated NPs alone. Those patients enrolled by NP criteria were older and more commonly White persons with lower body mass index, lower NYHA class, less diabetes, more atrial fibrillation, and lower baseline PAP. Event rates were lower among those patients in the NP group for both the full follow-up (40.9 per 100 patient-years vs 82.0 per 100 patient-years) and the pre-COVID-19 analysis (43.6 per 100 patient-years vs 88.0 per 100 patient-years). The effects of hemodynamic monitoring were consistent across enrollment strata for the primary endpoint over the full study duration (interaction P = 0.71) and the pre-COVID-19 analysis (interaction P = 0.58). CONCLUSIONS: Consistent effects of hemodynamic-guided HF management across enrollment strata in GUIDE-HF support consideration of hemodynamic monitoring in the expanded group of patients with chronic HF and elevated NPs without recent HFH. (Hemodynamic-Guided Management of Heart Failure [GUIDE-HF]; NCT03387813).

Effect of Early Amiodarone Use on Warfarin Sensitivity, Blood Product Use, and Bleeding in Patients With a Left Ventricular Assist Device.

Data are scarce on the effect of amiodarone on warfarin sensitivity and related outcomes after placement of a left ventricular assist device (VAD). This retrospective study compared 30-day outcomes between patients on amiodarone vs no amiodarone after VAD implant. After exclusions, 220 patients received amiodarone and 136 patients did not. Compared to the no amiodarone group, the amiodarone group had a higher warfarin dosing index (0.53 [0.39, 0.79] vs 0.46 [0.34, 0.63]; P = 0.003), incidence of INR ≥ 4 (40.5 vs 23.5%; P = 0.001), incidence of bleeding (24.1 vs 14%; P = 0.021), and use of INR reversal agents (14.5 vs 2.9%, P ≤ 0.001). Amiodarone was associated with bleeding (OR, 1.95; 95% CI, 1.10-3.47; P = 0.022), but not after adjusting for age, estimated glomerular filtration rate, and platelet count (OR, 1.67; 95% CI, 0.92-3.03; P = 0.089). After VAD implant, amiodarone was associated with increased warfarin sensitivity and administration of INR reversal agents.

Management of hypertension in patients supported with continuous flow left ventricular assist devices.

PURPOSE OF REVIEW: Hypertension remains one of the most common clinical problems leading to devastating postleft ventricular assist device (LVAD) implant complications. This study reviews the pathophysiology of hypertension in the setting of continuous flow LVAD support and provides an update on currently available antihypertensive therapies for LVAD patients. RECENT FINDINGS: The true prevalence of hypertension in the LVAD population remains unknown. Effective blood pressure (BP) control and standardization of BP measurement are key to prevent suboptimal left ventricular unloading, pump malfunction and worsening aortic regurgitation. Angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB), beta blockers and mineralocorticoid receptor antagonists (MRA) are the preferred antihypertensive agents because of their additional potential benefits, including optimization of haemodynamics, prevention of stroke, gastrointestinal bleed and in some patients myocardial recovery. Angiotensin receptor-neprilysin inhibition (ARNI) may be a well tolerated and effective therapy for BP control especially among CF-LVAD patients with resistant hypertension. Similarly, sodium glucose co-transporter 2 inhibitors (SGLT2i) should be considered in the absence of contraindications. SUMMARY: Hypertension is very common post-LVAD implant. Heart failure guideline directed medical therapies, including ACEI, ARB, beta blockers and MRA, are the preferred antihypertensive agents to improve post-LVAD outcomes.

Preimplant Hyponatremia Does Not Predict Adverse Outcomes in Patients With Left Ventricular Assist Devices.

Hyponatremia is a well-established marker of adverse outcomes in chronic heart failure (HF) but not well studied in patients with left ventricular assist device (LVAD). This is a retrospective study, single center study of HM3 [Abbott, USA] LVAD implants. We divided our population based on their sodium prior to LVAD implantation - hyponatremia if <135 mEq/L and normal sodium if 135-145 mEq/L. We compared postoperative and long-term outcomes. A total of 195 patients were included, preimplant hyponatremia was present in 40% with a sodium of 132.1 ± 2.1 vs 137.8 ± 1.9 mEq/L in the normal sodium group. No differences were observed in the postoperative or long-term outcomes. Preimplant hyponatremia was not associated with mortality or HF admissions, likely due to adequate left ventricular unloading and resolution of the mechanisms that lead to hyponatremia. These results suggest that optimization of mild hyponatremia may not be critical and should not delay LVAD placement.

New concepts in heart failure with preserved ejection fraction and hypertension.

PURPOSE OF REVIEW: Hypertension (HTN) remains the most common and strongest contributing factor to the development of heart failure with preserved ejection fraction (HFpEF). In this review, we aim to summarize the pathophysiological processes linking HTN to HFpEF and highlight novel concepts in medical and device-based management of HFpEF and HTN. RECENT FINDINGS: Despite the global increase in the prevalence of HFpEF, there has been limited benefit in current medication and device-based therapy for this complex syndrome. The hallmark of HFpEF is an elevated left intra-atrial and ventricular pressure and exertional dyspnea. Traditional medications used for treating HTN in patients with reduced left ventricular ejection fraction have unclear benefits in patients with HFpEF. Careful analysis of emerging medications such as angiotensin receptor-neprilysin inhibitor and sodium-glucose co-transporter-2 inhibitors showed benefit in reducing not only blood pressure but also hospitalizations in patients with HFpEF. Current data on device-based therapy aims to reduce left intra-atrial pressure, ventricular pressure and stimulate baroreceptors to lower blood pressure; however, needs further investigation. SUMMARY: The nexus of HTN and HFpEF remains strong and complex. Although traditional medications for treating HFrEF did not affect long-term outcomes, novel therapies with angiotensin receptor neprilysin-inhibitor and sodium-glucose co-transporter-2 inhibitor offer promising results. Many device-based interventions in the HFpEF population are being developed with the aim to reduce left intra-atrial and ventricular pressure; however, their role in HFpEF hypertensive patients needs to be further investigated.

COVID-19 Myocarditis: An Emerging Clinical Conundrum.

Coronavirus Disease 2019 (COVID-19) has been a significant cause of global mortality and morbidity since it was first reported in December 2019 in Wuhan, China. COVID19 like previous coronaviruses primarily affects the lungs causing pneumonia, interstitial pneumonitis, and severe acute respiratory distress syndrome (ARDS). However, there is increasing evidence linking COVID-19 to cardiovascular complications such as arrhythmias, heart failure, cardiogenic shock, fulminant myocarditis, and cardiac death. Given the novelty of this virus, there is paucity of data on some cardiovascular complications of COVID-19, specifically myocarditis. Myocarditis is an inflammatory disease of the heart muscle with a heterogenous clinical presentation and progression. It is mostly caused by viral infections and is the result of interaction of the virus and the host's immune system. There have been several case reports linking COVID-19 with myocarditis, however the true mechanism of cardiac injury remains under investigation. In this paper we review the clinical presentation, proposed pathophysiology, differential diagnoses and management of myocarditis in COVID-19 patients.

Biomarkers in heart failure: Relevance in the clinical practice.

Early detection and risk stratification of patients with heart failure (HF) are crucial to improve outcomes. Given the complexity of the pathophysiological processes of HF and the involvement of multi-organ systems in different stages of HF, clinical prognostication of HF can be challenging. In this regard, several biomarkers have been investigated for diagnosis, screening, and risk stratification of HF patients. These biomarkers can be classified as biomarkers of myocardial stretch such as B-type natriuretic peptide, biomarkers of neurohormonal activation, biomarkers of inflammation and oxidative stress and biomarkers of cardiac hypertrophy, fibrosis and remodeling. In this paper, we summarize current evidence supporting the use of selected biomarkers in HF. We review their diagnostic, prognostic and therapeutic role in the management of HF. We also discuss potential factors limiting the use of these novel biomarkers in the clinical practice and highlight the challenges of adopting a multi-biomarker strategy.

Cerebral protection during percutaneous intervention for left ventricular assist device outflow graft obstruction.

BACKGROUND: Left ventricular assist devices (LVAD) outflow graft obstruction is an uncommon complication but carries significant morbidity and mortality. Here we provide a case series of patients with LVAD intrinsic outflow graft obstruction who are deemed to be a high surgical risk for pump exchange and, therefore, underwent percutaneous intervention with the concomitant use of neuroprotective device-Sentinel cerebral protection system (CPS) (Boston Scientific) to prevent embolic stroke. METHODS: We retrospectively analyzed patients who underwent LVAD placement in our institution and developed LVAD outflow graft obstruction. The diagnosis of LVAD outflow graft obstruction was confirmed by utilizing various cardiac imaging modalities such as echocardiography and/or computed tomography angiography. All patients were treated with percutaneous intervention and a catheter-based CPS. RESULTS: From a total of 501 LVAD implants in our institute, 6 (1.2%) patients with LVAD outflow graft obstruction who underwent percutaneous treatment were included; 4 patients with HeartMate-III LVAD, 1 patient with HeartMate-II LVAD, and 1 patient with HeartWare (HVAD). The median age of patients was 56.5 years at the time of LVAD implantation. The median time from the LVAD implantation to the episode of LVAD outflow obstruction was 1343 days. Utilization of Sentinel CPS resulted in the capture and removal of thrombus/debris in all patients. CONCLUSIONS: Percutaneous intervention of LVAD outflow graft obstruction is less invasive than surgical pump exchange and an acceptable alternative in properly selected patients. In our experience, utilization of a catheter-based CPS can help in reducing the incidence of periprocedural embolic events.

Triple Antithrombotic Therapy in Patients With Left Ventricular Assist Devices.

Data on the efficacy and safety of the combination of warfarin and dual-antiplatelet therapy compared with warfarin and mono-antiplatelet therapy (MAPT) in patients with left ventricular assist devices (LVAD) remains scarce. Single-center study of 130 consecutive patients with durable LVAD. Baseline demographics, antithrombotic and antiplatelet regimen, and outcomes were compared between patients receiving warfarin plus dual-antiplatelet therapy (Group 1) and warfarin plus MAPT (Group 2). Antiplatelet therapy was assessed at hospital discharge post-LVAD implant and included aspirin, clopidogrel and dipyridamole. Outcomes at 1-year were assessed in each group. All patients were on aspirin and warfarin. No significant differences with regards to age, gender or ethnicity were noted at baseline between the two groups. Group 1 was more likely to have higher lactate dehydrogenase LDH levels at discharge and a history of stroke. No significant differences in international normalized ratio INR, hemoglobin or hematocrit were noted at discharge. During the study period, 48 patients had gastrointestinal bleeding events: 28 of 68 (41.2%) in Group 1 vs 20 of 62 (32.2%) in Group 2 (P = 0.293). At 1year, no statistically significant differences were noted in gastrointestinal bleeding (Group 1=27.90% vs Group 2 = 25.80, P = 0.784), ischemic stroke (Group 1 = 8.8% vs group 2 = 6.5%, P = 0.612), hemorrhagic stroke (Group 1 = 4.4% vs group 2 = 3.2%, P = 0.725) or mortality (Group 1 = 5.9% vs Group 2 = 1.6%, P = 0.206). Rates of pump thrombosis however were lower in Group 1 (Group 1 = 0% vs Group 2 = 6.5%, P = 0.033). Our study showed a high prevalence of triple-therapy antithrombotic use in LVAD patients with no significant differences in bleeding, stroke or survival. However, the risk for pump thrombosis was lower at 1-year when compared to patient receiving MAPT.

Feasibility and Safety of Coronary Angiography via Radial Approach in Cardiac Transplant Recipients: A Single Center Experience.

Coronary angiography remains the gold standard post-transplant screening test for cardiac allograft vasculopathy. This procedure has traditionally been performed via femoral approach. Data on safety and efficacy of radial approach in cardiac transplant patients remains scarce. Single center retrospective study including all cardiac transplant patients who underwent coronary angiography via transradial approach (TRA) or transfemoral approach (TFA). Safety and efficacy outcomes were compared between the 2 groups. Primary end points included major bleeding, vascular complications, crossover to femoral approach, contrast use and radiation exposure. A total of 201 patients were included. 96 patients (47.8%) underwent angiography via TRA. At baseline, no significant differences with regards to age, gender, or traditional risk factors such as HTN, DM, hyperlipidemia were noted between the 2 groups. Most patients underwent intravascular ultrasound (n = 179, 89%) with no statistically significant differences between the 2 groups (TRA: 90.6% vs TFA: 87.6%, P = 0.5). Additionally, there were no statistically significant differences in radiation exposure, amount of contrast use and fluoroscopy time between the 2 groups. Although there were trends toward increased bleeding among TFA group, these were not statistically significant and were mostly driven by access site hematomas. Use of TRA increased over time and Conversion from TRA to TFA was low (n = 4, 4.2%). Coronary angiography via the radial approach in cardiac transplant recipients is feasible, safe and is associated with low a risk of bleeding with no significant increase in radiation exposure when compared to the traditional femoral approach.

A Simplified Diagnostic and Therapeutic Approach to Pulmonary Hypertension.

Pulmonary hypertension remains a common but complex disorder that physicians face in their daily practice. Pulmonary hypertension has been classified by the World Health Organization into five major categories according to etiology, pathophysiology, and hemodynamic properties. The clinical course and overall prognosis varies by etiology, therefore making the correct diagnosis is paramount to avoid delay in treatment and improve outcomes. This review aims to provide clinicians with a simplified diagnostic approach to pulmonary hypertension. We also provide a guide to risk stratification and when to refer patient to a pulmonary hypertension expert center.