Heart failure (HF) is one of the leading causes of morbidity and mortality globally, with 23 million patients suffering from this entity. The prevalence increases with age and comorbidities, and its burden affects the healthcare system worldwide. ^{1 , 2} In Brazil, the estimated burden of HF affects 2 million individuals, with an incidence of 240,000 new cases annually. ³ In recent decades, there has been important progress in drug therapy and the widespread use of implantable cardioverter defibrillators (ICDs) and cardiac resynchronization therapy (CRT) devices, which have improved the prognosis of patients with HF. ^{4 , 5} However, morbidity rates remain high, with an estimated five-year mortality of more than 50% associated with high re-hospitalization rates. ^{1 , 2 , 4 , 5} In this sense, in recent years, several transcatheter implantable devices have emerged intending to improve the prognosis and quality of life in HF. The main transcatheter devices available for minimally invasive cardiac monitoring, as well as for the adjuvant treatment of advanced chronic HF, are summarized in the Central Figure. Treatments aimed at valve etiologies of HF are not addressed in this review.

The Corvia interatrial shunt device (IASD) system II® (Corvia Medical Inc., Tewkesbury, Massachusetts, USA) consists of a nitinol device (19 mm outside diameter) percutaneously inserted into the interatrial septum to produce an 8 mm atrial septal defect ( Table 2 ). The device was designed after testing its potential hemodynamic effects using a computational model of HF. ⁴²

Initial experience with this device included 11 patients with chronic HF, NYHA > II, LVEF ≥ 45%, and pulmonary capillary wedge pressure (PCWP) ≥ 15 mmHg at rest or ≥25 mmHg at exercise. The device was successfully implanted using the transfemoral approach in all patients without complications. At 30 days, the control echocardiogram did not show device displacement, and left-to-right shunt patency was verified in 10 patients (91%). In the remaining patient, the flow direction could not be determined. There was a significant improvement in PCWP (p= 0.005), quality of life (p= 0.005), and 6MWT (p= 0.025) at 30 days. ⁴³

The single-arm, phase I prospective study called REDUCE LAP-HF (Reduced Elevated Left Atrial Pressure in Patients With Heart Failure I) ^{44 , 45} included 64 patients with symptomatic HF (NYHA II [n = 18] or III [n = 46]), LVEF > 40% (mean LVEF of 47 ± 7%, LV end-diastolic volume of 68 ± 13 ml/m ² , with ischemic etiology in 23 patients (36%). At 12-month follow-up, there were 17 hospitalizations for HF in 13 patients and 3 deaths (pneumonia, fatal stroke, and an undetermined cause), with a 95% 1-year survival rate. NYHA functional class, quality of life (Minnesota CI score), and the 6MWT all had significant and sustained improvements after 1 year (all with p<0.01). ⁴⁵ At the control echocardiogram (n=48), LVEF remained unchanged, but there was a significant reduction in the indexed left and right ventricle end-diastolic volumes. The Qp: Qs ratio (1.25 ± 0.25) remained unchanged at 12 months. These studies demonstrated that this new therapy for HF is feasible, safe, and effective in improving symptoms in patients with HF with preserved or moderately reduced LVEF, but it is still unclear whether the improvement is persistent in the longer term and whether this therapy can improve survival in patients with refractory HF. Subsequently, the sham-controlled, double-blind, phase II study called REDUCE LAP-HF I ^{46 , 47} included HF patients with LVEF > 40% and increased left atrial pressure. A total of 44 patients were randomized 1:1 to the control group (n=22) or treatment group (n=22); both underwent placement of the femoral introducer, but only the treatment group performed the transseptal puncture and placement of the IASD. In the first month, there was a significant reduction in PCWP during exercise in the treatment group (p= 0.028). ⁴⁶ At the 6-month follow-up, there was an increase in the diameter of the right ventricle in the treatment group, compatible with a left-to-right shunt (IASD: 7.9 mL/m ² vs. control: −1.8 mL/m ² ; p= 0.002). At the 1-year follow-up, shunt patency was confirmed in all patients, and the procedure was safe. There was a trend towards a reduction in the rates of hospitalizations for HF or visits requiring intravenous diuretic therapy (IASD: 0.22 patient/year, 95%CI 0.08-0.58 vs. control: 0.63 patient/year, 95%CI 0.33-1.21; p= 0.06), but the study lacked statistical power due to the very small sample. ⁴⁷

The REDUCE LAP-HF II trial is a randomized, double-blind, sham-controlled study that included 626 patients with symptomatic HF, with EF ≥ 40%, PCP > 25mmHg during exercise, and divided into device group (n=314) and sham (n=312). The mean age was 72 years (IQR 66-77), mostly female (62%), with mean LVEF = 60% (IQR 55-65), NYHA III (77%), and 42% using more than one diuretic. In the 691-day follow-up (IQR 389–809), there was an improvement in NYHA at 1 year in the device group (p=0.006), although with no difference between groups in the rate of HF-related events or improvement in quality of life by the Kansas questionnaire. ⁴⁸ In pre-specified analysis, the highest rate of events in the device group were the following subgroups: (1) male sex (95%CI 1.01–1.71; p= 0.02), (2) higher indexed volumes of the right atrium (95%CI 1.08–1.90; p= 0.012), (3) pulmonary systolic arterial pressure (PSAP) > 70 mmHg (95%CI 1.10-1.79; p= 0.002). Subgroups with intermediate LVEF (40-49%) and reduction in left ventricular global longitudinal strain (higher degree of systolic dysfunction) tended to have non-significant higher rate of events (p= 0.20 and 0.37, respectively).

In summary, patients treated with the Corvia device initially presented with enlargement of the right atrial and ventricular cavities, with subsequent reduction of the left ventricular cavity and maintenance of shunts throughout the follow-up period. Although studies have demonstrated a reduction in PCWP, improvement in symptoms and quality of life, and LV remodeling by echocardiogram, the larger randomized study showed less consistent results and the need for more robust data to be recommended in daily practice.

With the approval of the IASD in the European Union (CE Mark), the real-world registry called REDUCE LAP-HF III (NCT03191656) was created, which intends to include, by mid-2023, a total of 500 patients with HF, LVEF ≥ 40 %, increased left atrial pressures, which remain symptomatic despite optimized clinical therapy. Other ongoing clinical registries are the REDUCE LAP-HF IV (NCT04632160) and the REDUCE LAP-HFrEF (NCT03093961).

The V-Wave IASD (V-Wave Ltd, Akiva, Israel) consists of an hourglass-shaped nitinol structure encapsulated in polytetrafluoroethylene, which is implanted in the interatrial septum through a transseptal puncture ( Table 2 ). Inside, there is a porcine pericardial valve, which allows a unidirectional flow from left to right according to the increase in pressure in the left atrium, with a minimum lumen size of 5 mm ( Table 2 ). ⁴⁹

The V-Wave device was initially evaluated in an experimental sheep model of ischemic HF, ⁵⁰ being the first patient treated in October 2013. ⁴⁹ The first prospective study included 10 patients, all with chronic systolic HF (LVEF <40%), NYHA ≥III despite optimized medical treatment, and PCP ≥ 15 mmHg. The V-Wave device was successfully implanted in all patients without complications. Treatment at hospital discharge was anticoagulation with warfarin in 7 cases and direct anticoagulants (DOACS) in 3 cases. No device-related adverse events occurred. One patient had warfarin-related gastrointestinal bleeding 2 months after the procedure, and another patient with an LVEF of 15% and a history of ventricular arrhythmias had multiple episodes of symptomatic ventricular tachycardia that required hospitalization and ablation therapy 5 weeks after the procedure. This patient continued to deteriorate the following weeks after hospitalization and died of terminal HF. At follow-up, transesophageal echocardiography at 1 month and transthoracic echocardiography at 3 months showed residual left-to-right atrial shunt in all patients. No thrombus or device migration was documented. At the 3-month follow-up, there was a significant reduction in PCWP (23 vs. 17 mmHg; p= 0.035), with improvement in the 6MWT (244 vs. 318m, p= 0.016) and quality of life according to the Kansas questionnaire (p= 0.0001). In addition, there was a significant reduction in left ventricular systolic and diastolic diameters at 3 months, despite maintained bi-ventricular function, as well as stable Nt-pro-BNP levels at follow-up. ⁵¹

The V-WAVE SHUNT study (VW-SP-1; NCT01965015) has the longest follow-up, with 38 patients, NYHA class III or IV, including HFrEF (n=30) and HFpEF (n=8). The device was successfully implanted in all patients, with only 1 case of tamponade, which reverted with pericardial drainage. At 3 and 12 months of follow-up, there was an improvement in NYHA functional class [classes I (78%) or II (60%)], quality of life (improvement >5 points in 74% and 73% of patients, respectively) and in the 6MWT (mean increases of 41±63 and 28±83 meters, respectively), all with p <0.02. All shunts were patent at 3 months; however, at 12 months, 5 of 36 (14%) were occluded, and another 13 of 36 (36%) were stenotic. Patients with widely patent shunts had lower rates of long-term death, need for a left ventricular assist device or heart transplant (p < 0.001), and hospitalization for HF (p < 0.008), along with a reduction in PCP (from 23.3±5.4 mmHg at baseline to 18.0±4.0 mmHg at 12 months; p=0.011). No objective changes were detected in the measures of the function of the right cavities. ⁵²

The ongoing RELIEVE-HF, multicenter, randomized, double-blind clinical trial (NCT03499236) includes 605 patients, randomized 1:1 to implantation of the V-wave IASD vs. control group. The control group underwent right heart catheterization and echocardiography to assess anatomy, while the treatment group underwent transseptal puncture V-Wave device placement. All cases will be followed up for 1, 2, and 5 years, with results estimated soon.

Initial data with V-Wave demonstrated that creating a left-to-right shunt with the implantation of a valved device in the septum is safe and effective, with improvement in clinical and hemodynamic outcomes in the short and medium term. Larger randomized trials with a greater number of patients are needed to confirm these initial findings and determine the long-term patency of the devices.

The AFR (Mia Medical, Istanbul, Turkey) is a self-expanding nitinol double-disk device with a 1-2 mm waist and central fenestration. It is available in fenestrated diameters of 6, 8, and 10 mm, with a total diameter of 18, 24, and 30 mm, and was initially used in patients with pulmonary arterial hypertension, creating a right-to-left shunt and causing an improvement in cardiac output, at the expense of desaturation. ⁵³ The left-to-right shunt caused by AFR is being tested in the context of HF in the multicenter European prospective pilot study called AFR-PRELIEVE (NCT03030274). Inclusion criteria are patients with symptomatic NYHA III or IV HF and pulmonary hypertension (PCWP ≥15 mmHg at rest or > 25 mmHg at exercise), regardless of LVEF. The primary endpoint is safety at 90 days, and the secondary endpoint of clinical efficacy and safety at 360 days. At the 3-month follow-up, improvement in symptoms and HF parameters was demonstrated. ⁵⁴ The 12-month follow-up was published in 2021, and the patients presented a mean age of 70 years, NYHA III in 93%, mean LVEF of 30% (IQR 29-35), with 53 devices successfully implanted [HFrEF (n=24) and HFpEF (n=29)]. Shunt patency was demonstrated in 92% (47/51) of cases, PCWP drop of 5 mmHg (p= 0.0003), and 11% (6/53) of death within 1 year. ⁵⁵

Other atrial shunt devices stand out, although preliminary data are restricted to a few patients. Alleviant system (Alleviant Medical, Austin, Texas, USA) is being evaluated in patients with HFpEF/HFmrEF, NYHA ≥ II, and LVEF >40%, in phase 1 and phase 2 studies: Alleviate-HF-1 (NCT04583527) and Alleviate- HF-2 (NCT04838353), with a follow-up of up to 12 months. Creating a no-implant interatrial shunt using the Alleviant System was initially evaluated in 28 patients; the mean age was 68 ± 9 years, and 68% were female. All procedures displayed technical success with left-to-right flow (shunt diameter 7.1±0.9 mm). Mean 6-minute walk distance increased by 101±71 meters (p < 0.001); quality of life increased by 26±19 points (p < 0.001); NT-proBNP decreased 372 ± 857 pg/mL (p = 0.018); and shunt patency was confirmed with unchanged diameter. ⁵⁶ The TASS - Transcatheter Atrial Shunt System (Edwards Lifesciences, Irvine, CA, USA) is a left-to-right shunt device via the coronary sinus. The coronary sinus (CS) is accessed and punctured to the left atrium (LA) through a right internal jugular vein puncture. The TASS device is positioned at the puncture site and causes LA decompression. The initial study included 11 patients, with the device being successfully implanted in 8 cases. In the 201-day follow-up (IQR 156-260), there was an improvement in NYHA class (I or II in 87.5%) and PCWP (9 mmHg; IQR 9.5-8.0 mmHg), with the maintenance of the shunt (Qp/Qs 0.25; IQR 0.19-0.33). ⁵⁷

The autonomic nervous system (ANS) is part of the regulation and homeostasis of cardiac function determined by a complex interaction between the sympathetic nervous system (SNS) and parasympathetic nervous system (PNS), together with regional and feedback responses by the central nervous system. In chronic HF, constant stimulation of the SNS has deleterious effects, with stress induced by tachycardia, elevated afterload, increased oxygen consumption, and ventricular remodeling. Other deleterious effects of the ANS imbalance are tachycardia and lower heart rate variability; both correlated with increased mortality in HF. ⁵⁸ Increased sympathetic activation and reduced parasympathetic tone may occur due to reduced sensitivity to the carotid baroreceptor reflex, as well as reduced heart rate variability. These factors may contribute to the progression of HF, meaning they should be considered treatment targets.

The increase in parasympathetic tone by (1) stimulation of the vagus nerve, (2) baroreceptor stimulating therapy in the carotid sinus, or (3) stimulation of the thoracic aorta has been recently evaluated, as summarized in Table 3 .

Table 3

Device	CardioFit	Barostim Neo	Harmony (HASS)
Indication	HFrEF	HFrEF	HFrEF or HFmrEF
Method of vagal stimulation	Bidirectional (efferent and afferent)	Afferent	Afferent
Electrode location	Cervical vagus nerve, 3 cm below the bifurcation of the carotid artery	Carotid sinus	Thoracic aorta
Trials	INOVATE-HF (2016): - n=707, FU= 16 months - Inclusion: EF ≤ 40%, NYHA III - did not change the 1a composite EP of death or HF-related events - improvement in NYHA, quality of life, and 6MWT (p< 0.05 for all) - no change in iLVEsV	HOPE4HF (2015): - n=146, FU= 6 months - Inclusion: EF ≤ 35%, NYHA III - Results: significant improvement in 6MWT, quality of life, NT pro-BNP, NYHA - no difference in hospitalization for HF (p= 0.08) BeAT-HF (2020): n=408, FU= 6 months - Inclusion: EF ≤ 35, NYHA II-III - Results: significant improvement in 6MWT, quality of life, NT pro-BNP (p< 0.01 for all)	ENDO-HF (in progress): - n=30, FU 6 months, phase II - Inclusion: EF ≥ 40%, NYHA II-III, NT pro-BNP > 300 pg/mL

HFrEF: heart failure with reduced ejection fraction; HFmrEF: heart failure mid-range ejection fraction; FU: follow-up; EF: left ventricular ejection fraction; NYHA: functional class by the New York Heart Association; EP: endpoint; HF: heart failure; 6MWT: 6-minute walk test; iLVEsV: indexed left ventricular end-systolic volume; NT-ProBNP: N-terminal fragment of type B natriuretic peptide.

The objective of VNS in HF is to increase parasympathetic tone. VNS has been successfully used in animal models, demonstrating that vagal stimulation caused a reduction in heart rate, preventing the occurrence of ventricular tachycardia after acute myocardial infarction in dogs. ⁵⁹ In the pilot study with CardioFit ^TM (BioControl Medical Ltd, Yehud, Israel), the device was successfully implanted in 8 patients, demonstrating feasibility, safety, and tolerability. ⁶⁰ CardioFit is positioned on the cervical topography of the vagus nerve, with an electrode in the right ventricle (RV) to regulate the heart rate and avoid excessive bradycardia through stimulation in the RV. In the multicenter, single-arm, phase II, CardioFit study, De Ferrari et al. ⁶¹ studied 32 patients with significant systolic dysfunction (mean LVEF of 23 ± 8%), mean age of 56±11 years and NYHA functional class II-IV. The device was associated with improvements in functional class, quality of life, LVEF (22 ± 7 to 29 ± 8%), and LV end-systolic volume, with results maintained at 12 months. The INOVATE-HF ⁶² clinical study included 707 patients with NYHA III HF and LVEF < 40%, randomized 3:2 to the CardioFit device implant group (n=436) or control group (n=271). At the 16-month follow-up, there was an improvement in NYHA, quality of life, and 6MWT in the CardioFit group (p< 0.05 for all), although with no difference in the primary composite outcome of death or HF-related events. Completed in 2014, using the first generation of ENV LivaNova (formerly Cyberonics), VNS Therapy System (LivaNova, Houston, Texas), the phase 2 ANTHEM-HF study included 60 patients with HFrEF (LVEF < 40%), NYHA II-III and LV end-diastolic diameter (LVDD) between 50-80 mm. They were submitted to cyclic and continuous vagus nerve stimulation with an amplitude of 1.5-3.0mA. At a 6-month follow-up, efficacy was demonstrated by an improvement in LVEF by 4.5% (95%CI of 2.4 to 6.6), a reduction in LV end-systolic volume of 4.1 mL (95%CI -9.0 to 0.8) and reduction in LV end-systolic diameter by 1.7 mm (95%CI -2.8 to -0.7). Furthermore, at 6 months, there were improvements in both NYHA (in 77%) and 6MWT (in 56 minutes, 95%CI 37-75) maintained at the late follow-up of 42 months. ^{63 , 64} In the randomized phase 2 study NECTAR-HF (n=96) patients with LVEF <35%, LVDD= 55 mm, and NYHA II-III were tested for the VNS (Boston Scientific, Massachusetts, USA). The device presented many adverse effects (cough and neck pain). No significant improvements were observed in cardiac remodeling or functional capacity, but there was an improvement in quality of life at 6 months and 18 months follow-up. ^{65 , 66} Among the 4 largest VNS studies (CardioFit, INOVATE-HF, ANTHEM-HF, and NECTAR-HF), we can observe a safety profile with improvements in functional class and quality of life. However, CardioFit and ANTHEM-HF demonstrated improvements in echocardiographic parameters (such as LVEF), while INOVATE-HF and NECTAR-HF had no differences between treatment and control groups. ⁶⁷ Finally, the single-arm ANTHEM-HFrEF study (NCT03425422), using the second-generation LivaNova device, VITARIA System (LivaNova USA, Inc, Houston, TX), is ongoing, including symptomatic HF with LVEF ≤35%, NYHA III, LVDD ≤ 80 mm and NT-proBNP ≥800 pg/mL, with a plan to recruit 800 patients. ⁶⁸ One consideration is that the vagus nerve comprises 20% efferent fibers and 80% afferent fibers. The influence of afferent fibers still needs to be evaluated more appropriately for the best performance of VNS.

The parasympathetic nervous system innervates the carotid body and sinus through vagus, glossopharyngeal fibers, and the sympathetic nervous system via cervical sympathetic ganglia (stellate ganglion). Stimulation of carotid sinus mechanoreceptors causes attenuation of the SNS and increased vagal tone. Devices using BAT are available in Table 3 . Carotid sinus stimulation with the Barostim Neo device (CVRx, Inc., Minneapolis, Minnesota, USA) was evaluated in the phase II study HOPE4HF, published in 2015. ⁶⁹ Barostim consists of an electrode in the carotid sinus, associated with a pulse generator, which is implanted subcutaneously in the infraclavicular region. This randomized, multicenter study included 146 patients with NYHA III and LVEF ≤ 35%, 70 in the control and 76 in the treatment group, followed for 6 months. The treatment group presented significant improvement in the 6MWT (59.6 ± 14 m vs. 1.5 ± 13 m; p=0.004), quality of life (–17.4 ± 2.8 points vs. 2.1 ± 3.1 points; p < 0.001), NT-Pro-BNP and NYHA functional class, with no difference in days of hospitalization for HF (p= 0.08) or LVEF. ⁶⁹ The data were consistent at 6 and 12 months; ⁷⁰ in addition, BAT had more pronounced results in those without CRT, and there was no difference between the presence or absence of coronary artery disease. ^{71 , 72} In BeAT-HF, ⁷³ multicenter phase III study, with n=408, including patients with NYHA II-III HF and LVEF < 35%, consistent results were shown, with improvement in 6MWT, quality of life, and NT pro-BNP values. Thus, the American FDA and CE Mark approved BAT for patients with HFrEF, class II-III, with NT-pro-BNP < 1,600 or ineligibility for cardiac resynchronization therapy. Stimulation of the descending thoracic aorta also involves the baroreceptor system and is being evaluated in the ENDO-HF study (NCT02633644), with HASS technology - Harmony Aortic Stimulator System (Enopace Biomedical, Israel). A wireless system remotely configures this device and consists of a nitinol-coated stent structure containing electrodes and a receptor antenna to suppress the sympathetic tone by pressure waves in the aortic wall, resulting in reduced heart rate and peripheral vasoconstriction. The ENDO-HF study (NCT02633644) aims to follow 30 patients over 6 months, having the following inclusion criteria: HF with NYHA II-III, LVEF ≥ 40%, heart rate between 60-110 bpm and NT-proBNP >300 pg/mL. The first case described in the literature with Harmony showed safety, with (1) symptomatic improvement, demonstrated by NYHA, 6MWT, and reduction of NT-proBNP values, as well as (2) favorable changes in the heart structure, with a reduction in the indexed volume of the left atrium (41.3 to 31.6 mL/m ² ), increase in the LA reservoir strain by 40% and improvement in the diastolic function of LV. This data was consistent at 6 months and maintained at 1 year. ⁷⁴

Recent data support that catheter-based renal denervation (RDN) presents a safe and minimally invasive treatment option for uncontrolled hypertension, a condition that is driven by increased sympathetic activity. The radiofrequency method can also have secondary beneficial effects such as reduced heart rate, insulin resistance, less apnea and hypopnea, and lower volume of tachyarrhythmias. ^{75 , 76} The reduction of sympathetic tone with drug therapy is already an established fact in the therapeutic armamentarium for HF. In this sense, RDN could not only inhibit neprilysin activity but also limit the activation of the renin-angiotensin-aldosterone system, resulting in lower circulating levels of angiotensin I and II. ⁷⁷ In this regard, the hypothesis was raised that RDN could have clinical benefits in patients with chronic HF.

The first-in-man safety evaluation of RDN in the context of chronic HF was performed in the open-label REACH trial, where 7 patients with HFrEF and blood pressure above 120 mmHg systolic underwent the RDN procedure. Patients with a mean age of 69, mean LVEF of 43%, and most with ischemic HF (71%). In the 6-month follow-up, the study found no procedural or post-procedural complications, with an increase of 6MWT despite no change in blood pressure. ⁷⁸ Considering this promising data, the RDN as HF therapy was evaluated with the Symplicity Spyral (Medtronic, Minneapolis, USA) in the SYMPLICITY-HF, ⁷⁹ prospective, multicenter study that included 39 patients with LVEF<40% and NYHA II-III, despite optimized medical therapy. The average age was 65±11 years, and 62% had ischemic HF. At 12 months, no improvements in LVEF or 6MWT were observed, despite small reductions in NT-ProBNP levels (1530 ± 1228 vs. 1428 ± 1844 ng/mL; p= 0.006) and oral glucose tolerance test in 120 minutes (11.2 ± 5.1 vs. 9.9 ± 3.6; p= 0.026). In this study, renal denervation was focused on the ostium and larger bifurcations and was not applied to the distal bifurcations. Another recent prospective and randomized study with the Celsius ThermoCool Catheter (Biosense Webster, Irvine, USA) device evaluated RDN in 60 patients with HF with LVEF< 40%, NYHA II or III, despite optimized medical therapy. ⁸⁰ Patients were randomly assigned in a 1:1 ratio to RDN group (n=30) or control group (n=30). After 6 months, the RDN group significantly improved LVEF, NYHA functional class, and NT-proBNP values (all with p < 0.001). Among other characteristics, it is noteworthy that patients had a lower body mass index (BMI) than in SYMPLICITY-HF, which may have influenced the distribution of nerve fibers eliminated during renal denervation therapy.

A meta-analysis of 11 studies involving RDN in HFrEF demonstrated a significant increase in LVEF, reduction in LV end-systolic diameter and reduction in left atrium diameter. ⁸¹ In a subgroup of patients with Chagas cardiomyopathy and HFrEF (average LVEF of 26.7 ± 4.9%), RDN was evaluated in a prospective, randomized pilot study with 17 patients, and the therapy was safe but underpowered for clinical outcomes due to the limited number of patients. ⁸²

The recent IMPROVE-HF-I trial is a single center open label prospective randomized controlled trial that evaluated RDN in the setting of HFrEF and assigned 50 patients with a LVEF≤ 35% and NYHA class ≥II, in a 1:1 ratio to either RDN and optimal medical therapy (OMT) or OMT alone. The device used for RDN was the Vessix V2 Renal Denervation System (Boston Scientific, Natick, MA, USA). The primary efficacy endpoint was the change in iodine-123 meta-iodobenzylguanidine (123I-MIBG) heart-to-mediastinum ratio (HMR) at 6 months. With a mean age of 60 ± 9 years, 86% male, and mean LVEF of 33 ± 8%, RDN with the Vessix device was safe but did not result in significant changes in cardiac sympathetic nerve activity at 6 months as measured using 123I-MIBG. ⁸³

In summary, RDN for HFrEF is safe, without any relevant complications, and may associate with improvements in LVEF, 6MWT, NYHA functional class, and NT-proBNP values and reduction of LV end-systolic diameter and left atrium diameter, although larger studies are warranted to confirm such findings.

In the context of HFpEF, hypertension remains the most common comorbidity, and its treatment with RDN could greatly impact HF management. The retrospective study by Kresoja et al. evaluated 164 hypertensive patients between 2011 and 2018 undergoing RDN with HFpEF (n=99) and without HF diagnosis (n=65). Pre-intervention, the HFpEF group had greater index stroke volume, vascular stiffness, and diastolic dysfunction than the non-HF group. After RSD, the hemodynamic changes in the HFpEF group were partially normalized, implying a possible role for RSD also in hypertensive HFpEF patients. ⁸⁴

Currently, there are several transcatheter percutaneous options for diagnosis and adjuvant treatment of chronic HF patients. Despite the significant improvement in the morbidity and mortality of these conditions, re-hospitalization and mortality rates remain high. Catheter-based interventions for HF offer potential solutions for managing and optimizing HF patients. They target some mechanistic and pathophysiological processes critical in the progression of heart failure, focusing on monitorization, left ventricular restoration, interatrial shunt, and neurohumoral activation. Preliminary results associated with most of these interventions have been promising, with improvements in hemodynamics, symptoms, quality of life, and functional status. However, data from most of these technologies are restricted to observational studies, including limited numbers of patients and relatively small randomized trials. Currently, the CardioMEMS monitoring device has the most robust data, having improved quality of life and reduced both HF hospitalizations and mean pulmonary arterial pressure, being incorporated into current guidelines. Randomized studies with larger numbers of patients and longer-term follow-ups will be necessary to provide definitive data on the effectiveness of these various devices in clinical practice.