Cardiac resynchronization therapy in heart failure based on Strauss criteria for left bundle branch block.

AIMS: The left bundle branch block (LBBB) is a strong predictor of response to cardiac resynchronization therapy (CRT). However, a significant number of patients do not respond to the treatment. The study sought to evaluate the impact of the stricter Strauss criteria for left bundle branch block (St-LBBB) on CRT response, hospitalizations, ventricular arrhythmia (VA) events and mortality. METHODS: This study is a retrospective analysis of prospectively collected data on heart failure (HF) patients with LBBB admitted for CRT implantation. Patients were divided into two groups according to the fulfilment or not of St-LBBB criteria. RESULTS: The study included 82 patients with ischaemic (ICM) and non-ischaemic (NICM) cardiomyopathy [46 (56%) with St-LBBB and 36 (44%) with non-St-LBBB]. Patients with St-LBBB showed higher CRT response rates compared with those with non-St-LBBB (P < 0.01), while the group with NICM exhibited the greatest benefit (P < 0.01). St-LBBB CRT responders displayed significantly lower rates of HF hospitalization (P < 0.0001) compared with the non-St-LBBB group. According to Kaplan-Meier time curves, this was primarily evident in patients with NICM (P < 0.0001). CRT responders displayed significantly fewer VA events (P < 0.001) and lower mortality rates (P < 0.0001) than non-responders. Kaplan-Meier estimates demonstrated a significantly lower incidence of VAs in NICM patients with St-LBBB (P = 0.049) compared with ICM patients with St-LBBB (P = 0.25). Lower mortality rates were observed in CRT responders than non-responders (P < 0.0001), with the group of NICM with St-LBBB criteria exhibiting the greatest benefit (P = 0.0238). CONCLUSIONS: Patients with NICM and St-LBBB present the greatest benefit concerning CRT response, HF hospitalizations, VA events and mortality. Although St-LBBB criteria seem to improve patient selection for CRT, more data are needed to elucidate the role of St-LBBB criteria in this setting.

The left ventricular assist device 'skeleton man': case report-simple tools for skeletal muscle evaluation and very early aerobic/resistance/inspiratory training in cardiac cachexia.

Background: Skeletal muscle wasting (SMW) is highly prevalent in patients with heart failure (HF) at left ventricular assist device (LVAD) implantation and is associated with morbidity and mortality. At the same time, SMW is clinically under-recognized, while exercise training (ET) studies in weak LVAD patients are lacking. Case summary: A 60-year-old man with advanced HF, SMW, cardiac cachexia, and frailty was confined in bed for 6 months initially supported with intravenous inotropes and subsequently with an intra-aortic balloon pump. His frailty was recognized as an LVAD-responsive frailty, and patient was successfully implanted with a HeartWare (Medtronic). Post-surgery, patient was very weak, unable even to move in bed without assistance. We evaluated skeletal muscle using simple tools such as the Oxford scale, mid-thigh circumference, hand-held dynamometry, and maximum inspiratory pressure. Physical performance was assessed with the sit to stand test, gait speed test, pedal bike timing, and the 6 min walk test. On top of routine physiotherapy, patient underwent an 8-week modified aerobic/resistance/inspiratory (ARIS) ET programme at moderate intensity and showed significant improvements in skeletal muscle mass and strength and physical and functional capacity. Discussion: We want to emphasize the importance of skeletal muscle evaluation at LVAD implantation and the feasibility and effectiveness of early ARIS training in very weak patients.

Incidence, risk factors and clinical outcome of multidrug-resistant organisms after heart transplantation.

BACKGROUND: Transplant recipients commonly harbor multidrug-resistant organisms (MDROs), as a result of frequent hospital admissions and increased exposure to antimicrobials and invasive procedures. AIM: To investigate the impact of patient demographic and clinical characteristics on MDRO acquisition, as well as the impact of MDRO acquisition on intensive care unit (ICU) and hospital length of stay, and on ICU mortality and 1-year mortality post heart transplantation. METHODS: This retrospective cohort study analyzed 98 consecutive heart transplant patients over a ten-year period (2013-2022) in a single transplantation center. Data was collected regarding MDROs commonly encountered in critical care. RESULTS: Among the 98 transplanted patients (70% male), about a third (32%) acquired or already harbored MDROs upon transplantation (MDRO group), while two thirds did not (MDRO-free group). The prevalent MDROs were Acinetobacter baumannii (14%), Pseudomonas aeruginosa (12%) and Klebsiella pneumoniae (11%). Compared to MDRO-free patients, the MDRO group was characterized by higher body mass index (P = 0.002), higher rates of renal failure (P = 0.017), primary graft dysfunction (10% vs 4.5%, P = 0.001), surgical re-exploration (34% vs 14%, P = 0.017), mechanical circulatory support (47% vs 26% P = 0.037) and renal replacement therapy (28% vs 9%, P = 0.014), as well as longer extracorporeal circulation time (median 210 vs 161 min, P = 0.003). The median length of stay was longer in the MDRO group, namely ICU stay was 16 vs 9 d in the MDRO-free group (P = 0.001), and hospital stay was 38 vs 28 d (P = 0.006), while 1-year mortality was higher (28% vs 7.6%, log-rank-χ 2: 7.34). CONCLUSION: Following heart transplantation, a predominance of Gram-negative MDROs was noted. MDRO acquisition was associated with higher complication rates, prolonged ICU and total hospital stay, and higher post-transplantation mortality.

Contemporary management of ventricular arrhythmias in heart failure.

Enhanced ventricular arrhythmogenesis is commonly experienced by patients in the end-stage of heart failure spectrum. A high burden of ventricular arrhythmias can affect the ventricular systolic function, lead to unexpected hospitalizations and further deteriorate the prognosis. Management of ventricular arrhythmias in this population is challenging. Implantable cardioverter-defibrillators are protective for the immediate termination of life-threatening arrhythmias but they have no impact in reducing the arrhythmic burden. Combination treatment with invasive (catheter ablation, mechanical hemodynamic support, sympathetic denervation) and noninvasive (antiarrhythmic drugs, medical therapy for heart failure, programming of implantable devices) therapies is commonly required. The aim of this review is to present the available therapeutic options, with main focus on recently published data for catheter ablation and provide a stepwise treatment approach.

Diagnostic and therapeutic dilemmas in a patient with myocarditis, Brugada syndrome and arrhythmic syncope.

We present a case of a previously healthy 23-year-old male who presented with chest pain, palpitations and spontaneous type 1 Brugada electrocardiographic (ECG) pattern. Positive family history for sudden cardiac death (SCD) was remarkable. Initially, clinical symptoms in combination with myocardial enzymes elevation, regional myocardial oedema with late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) and inflammatory lymphocytoid-cell infiltrates in the endomyocardial biopsy (EMB) suggested the diagnosis of a myocarditis-induced Brugada phenocopy (BrP). Under immunosuppressive therapy with methylprednisolone and azathioprine, a complete remission of both symptoms and biomarkers was accomplished. However, the Brugada pattern did not resolve. The eventually spontaneous Brugada pattern type 1 established the diagnosis of Brugada syndrome (BrS). Due to his previous history of syncope, the patient was offered an ICD that he declined. After his discharge he experienced a new episode of arrhythmic syncope. He was readmitted and received an ICD.

How does age affect outcomes after left ventricular assist device implantation: results from the PCHF-VAD registry.

AIMS: Use of left ventricular assist devices (LVADs) in older patients has increased, and assessing outcomes in older LVAD recipients is important. Therefore, this study aimed to investigate associations between age and outcomes after continuous-flow LVAD (cf-LVAD) implantation. METHODS AND RESULTS: Cf-LVAD patients from the multicentre European PCHF-VAD registry were included and categorized into those <50, 50-64, and ≥65 years old. The primary endpoint was all-cause mortality. Among secondary outcomes were heart failure (HF) hospitalizations, right ventricular (RV) failure, haemocompatibility score, bleeding events, non-fatal thromboembolic events, and device-related infections. Of 562 patients, 184 (32.7%) were <50, 305 (54.3%) were aged 50-64, whereas 73 (13.0%) were ≥65 years old. Median follow-up was 1.1 years. Patients in the oldest age group were significantly more often designated as destination therapy (DT) candidates (61%). A 10 year increase in age was associated with a significantly higher risk of mortality (hazard ratio [HR] 1.34, 95% confidence interval [CI] [1.15-1.57]), intracranial bleeding (HR 1.49, 95% CI [1.10-2.02]), and non-intracranial bleeding (HR 1.30, 95% CI [1.09-1.56]), which was confirmed by a higher mean haemocompatibility score (1.37 vs. 0.77, oldest vs. youngest groups, respectively, P = 0.033). Older patients suffered from less device-related infections requiring systemic antibiotics. No age-related differences were observed in HF-related hospitalizations, ventricular arrhythmias, pump thrombosis, non-fatal thromboembolic events, or RV failure. CONCLUSIONS: In the PCHF-VAD registry, higher age was associated with increased risk of mortality, and especially with increased risk of major bleeding, which is particularly relevant for the DT population. The risks of HF hospitalizations, pump thrombosis, ventricular arrhythmia, or RV failure were comparable. Strikingly, older patients had less device-related infections.

Sex-related differences in left ventricular assist device utilization and outcomes: results from the PCHF-VAD registry.

AIMS: Data on sex and left ventricular assist device (LVAD) utilization and outcomes have been conflicting and mostly confined to US studies incorporating older devices. This study aimed to investigate sex-related differences in LVAD utilization and outcomes in a contemporary European LVAD cohort. METHODS AND RESULTS: This analysis is part of the multicentre PCHF-VAD registry studying continuous-flow LVAD patients. The primary outcome was all-cause mortality. Secondary outcomes included ventricular arrhythmias, right ventricular failure, bleeding, thromboembolism, and the haemocompatibility score. Multivariable Cox regression models were used to assess associations between sex and outcomes. Overall, 457 men (81%) and 105 women (19%) were analysed. At LVAD implant, women were more often in Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profile 1 or 2 (55% vs. 41%, P = 0.009) and more often required temporary mechanical circulatory support (39% vs. 23%, P = 0.001). Mean age was comparable (52.1 vs. 53.4 years, P = 0.33), and median follow-up duration was 344 [range 147-823] days for women and 435 [range 190-816] days for men (P = 0.40). No significant sex-related differences were found in all-cause mortality (hazard ratio [HR] 0.79 for female vs. male sex, 95% confidence interval [CI] [0.50-1.27]). Female LVAD patients had a lower risk of ventricular arrhythmias (HR 0.56, 95% CI [0.33-0.95]) but more often experienced right ventricular failure. No significant sex-related differences were found in other outcomes. CONCLUSIONS: In this contemporary European cohort of LVAD patients, far fewer women than men underwent LVAD implantation despite similar clinical outcomes. This is important as the proportion of female LVAD patients (19%) was lower than the proportion of females with advanced HF as reported in previous studies, suggesting underutilization. Also, female patients were remarkably more often in INTERMACS profile 1 or 2, suggesting later referral for LVAD therapy. Additional research in female patients is warranted.

Improved survival of left ventricular assist device carriers in Europe according to implantation eras: results from the PCHF-VAD registry.

AIMS: Temporal changes in patient selection and major technological developments have occurred in the field of left ventricular assist devices (LVADs), yet analyses depicting this trend are lacking for Europe. We describe the advances of European LVAD programmes from the PCHF-VAD registry across device implantation eras. METHODS AND RESULTS: Of 583 patients from 13 European centres in the registry, 556 patients (mean age 53 ± 12 years, 82% male) were eligible for this analysis. Patients were divided into eras (E) by date of LVAD implantation: E1 from December 2006 to December 2012 (6 years), E2 from January 2013 to January 2020 (7 years). Patients implanted more recently were older with more comorbidities, but less acutely ill. Receiving an LVAD in E2 was associated with improved 1-year survival in adjusted analysis (hazard ratio [HR] 0.58, 95% confidence interval [CI] 0.35-0.98; p = 0.043). LVAD implantation in E2 was associated with a significantly lower chance of heart transplantation (adjusted HR 0.40, 95% CI 0.23-0.67; p = 0.001), and lower risk of LVAD-related infections (adjusted HR 0.64, 95% CI 0.43-0.95; p = 0.027), both in unadjusted and adjusted analyses. The adjusted risk of haemocompatibility-related events decreased (HR 0.60, 95% CI 0.39-0.91; p = 0.016), while heart failure-related events increased in E2 (HR 1.67, 95% CI 1.02-2.75; p = 0.043). CONCLUSION: In an analysis depicting the evolving landscape of continuous-flow LVAD carriers in Europe over 13 years, a trend towards better survival was seen in recent years, despite older recipients with more comorbidities, potentially attributable to increasing expertise of LVAD centres, improved patient selection and pump technology. However, a smaller chance of undergoing heart transplantation was noted in the second era, underscoring the relevance of improved outcomes on LVAD support.

Comparative analysis of LVAD patients in regard of ischaemic or idiopathic cardiomyopathy: A propensity-score analysis of EUROMACS data.

BACKGROUND: Despite recent advances in management of patients with advanced heart failure, mortality remains high. Aim of this study was to compare impact of different aetiology of ischaemic and idiopathic cardiomyopathy on early outcomes and long-term survival of patients after left ventricular assist device implantation. METHODS: European Registry for Patients with Mechanical Circulatory Support (EUROMACS) gathers clinical data and follow-up parameters of LVAD recipients. Patients enrolled in the EUROMACS registry with primary diagnosis of either ischaemic (n = 1190) or idiopathic (n = 812) cardiomyopathy were included. Primary Endpoints were early mortality as well as long-term survival. Secondary endpoint were major postoperative adverse events, such as need for rethoracotomy. Additionally, a propensity-score matching analysis was performed for patients with ischaemic (n = 509) and idiopathic (n = 509) cardiomyopathy. RESULTS: In terms of basic demographics and baseline parameters the two groups significantly differed as expected before propensity-score matching due to different aetiology of cardiomyopathy. Seven-day (52 (4.4%) versus 18 (2.2%); p = 0.009), 30-day (153 (12.9%) versus 73 (9.0%); p = 0.008) and in-hospital mortality (253 (19.7%) versus 123 (15.1%); p = 0.009) were significantly lower in the idiopathic cardiomyopathy group compared to the ischaemic cardiomyopathy group, whereas after propensity-score matching 30-day (p = 0.169) was comparable and in-hospital mortality (p = 0.051) was almost significant. Kaplan-Meier survival analysis revealed no significant difference in regard of long-term survival after propensity-score matching (Breslow-test p = 0.161 and LogRank-test p = 0.113). CONCLUSION: Though patients with ischaemic and idiopathic cardiomyopathy suffer from different cardiomyopathy aetiologies, 30-day-mortality and long-term survival of both groups were similar leading to the conclusion that covariates predominately influence mortality and survival of ischaemic and idiopathic cardiomyopathies.

Cardiovascular disease in women: Executive summary of the expert panel statement of women in cardiology of the hellenic cardiological society.

The perception that women represent a low-risk population for cardiovascular (CV) disease (CVD) needs to be reconsidered. Starting from risk factors, women are more likely to be susceptible to unhealthy behaviors and risk factors that have different impact on CV morbidity and mortality as compared to men. Despite the large body of evidence as regards the effect of lifestyle factors on the CVD onset, the gender-specific effect of traditional and non-traditional risk factors on the prognosis of patients with already established CVD has not been well investigated and understood. Furthermore, CVD in women is often misdiagnosed, underestimated, and undertreated. Women also experience hormonal changes from adolescence till elder life that affect CV physiology. Unfortunately, in most of the clinical trials women are underrepresented, leading to the limited knowledge of CV and systemic impact effects of several treatment modalities on women's health. Thus, in this consensus, a group of female cardiologists from the Hellenic Society of Cardiology presents the special features of CVD in women: the different needs in primary and secondary prevention, as well as therapeutic strategies that may be implemented in daily clinical practice to eliminate underestimation and undertreatment of CVD in the female population.

Cardiac implantable electronic devices with a defibrillator component and all-cause mortality in left ventricular assist device carriers: results from the PCHF-VAD registry.

AIMS: To compare characteristics of left ventricular assist device (LVAD) recipients receiving a cardiac implantable electronic device (CIED) with a defibrillator component (implantable cardioverter-defibrillator and cardiac resynchronization therapy with defibrillation, CIED-D) vs. those without one, and to assess whether carrying such a device contiguously with an LVAD is associated with outcomes. METHODS AND RESULTS: Overall, 448 patients were analysed (mean age 52 ± 13 years, 82% male) in the multicentre European PCHF-VAD registry. To account for all active CIED-Ds during ongoing LVAD treatment, outcome analyses were performed by a time-varying analysis with active CIED-D status post-LVAD as the time-varying covariate. At the time of LVAD implantation, 235 patients (52%) had an active CIED-D. Median time on LVAD support was 1.1 years (interquartile range 0.5-2.0 years). A reduction of 36% in the risk of all-cause mortality was observed in patients with an active CIED-D [hazard ratio (HR) 0.64, 95% confidence interval (CI) 0.46-0.91; P = 0.012), increasing to 41% after adjustment for baseline covariates (HR 0.59, 95% CI 0.40-0.87; P = 0.008) and 39% after propensity score adjustment (HR 0.61, 95% CI 0.39-0.94; P = 0.027). Other than CIED-D, age, LVAD implant as redo surgery, number of ventricular arrhythmia episodes and use of vasopressors pre-LVAD were remaining significant risk factors of all-cause mortality. Incident ventricular arrhythmias post-LVAD portended a 2.4-fold and 2.6-fold increased risk of all-cause and cardiovascular death, respectively; carrying an active CIED-D remained associated with a 47% and 43% reduction in these events, respectively. CONCLUSIONS: In an analysis accounting for all active CIED-Ds, including those implanted during LVAD support, carrying such a device was associated with significantly better survival during LVAD support.

A case report of recessive restrictive cardiomyopathy caused by a novel mutation in cardiac troponin I (TNNI3).

BACKGROUND: Restrictive cardiomyopathy is a rare cardiac disease, for which several genes including TNNT2, MYPN, FLNC and TNNI3 have been associated with its familial form. CASE PRESENTATION: Here we describe a female proband with a severely manifested restrictive phenotype leading to heart transplantation at the age of 41, who was found homozygous for the novel TNNI3 mutation: NM_000363.4:c.586G > C, p.(Asp196His). Her parents were third-degree cousins originating from a small village and although they were found heterozygous for the same variant they displayed no symptoms of the disease. Her older sister who was also found heterozygous was asymptomatic. Her twin sister and her brother who were homozygous for the same variant displayed a restrictive and a hypertrophic phenotype, respectively. Their children are all carriers of the mutation and remain asymptomatic until the age of 21. CONCLUSION: These observations point to a recessive mode of inheritance reported for the first time for this combination of gene/disease.

Phenotypic Heterogeneity within Members of a Family Carrying the Same RBM20 Mutation R634W.

OBJECTIVE: We present the genotypic and phenotypic characterization of a family displaying dilated cardiomyopathy (DCM). METHODS: The proband and his relatives underwent full cardiological assessment. Genetic analysis of the proband was performed with the use of next-generation sequencing technology. RESULTS: In this study, we present 6 members of a family carrying the RBM20 mutation NM_001134363.2:c.1900C>T. The proband was initially diagnosed with DCM at the age of 18 years and received an implantable cardioverter defibrillator (ICD) due to ventricular arrhythmias. His brother, carrier of the mutation, has been diagnosed with borderline left ventricular function. The mutation was shown to be of paternal origin, but their father remains asymptomatic with a mild DCM, while his electrocardiogram at the initial evaluation showed a right bundle branch block pattern. The mutation was also detected in the index case's aunt who was resuscitated from sudden cardiac death. Her echocardiography revealed early stages of DCM and a bicuspid aortic valve. Her children are both carriers of the mutation. Her daughter is unaffected, but her son has an ICD implanted due to sustained ventricular tachycardia and presents early signs of DCM. CONCLUSION: Our findings are the first report of co-segregation of the mutation in 6 family members, supporting its pathogenic role.

Advanced heart failure: a position statement of the Heart Failure Association of the European Society of Cardiology.

This article updates the Heart Failure Association of the European Society of Cardiology (ESC) 2007 classification of advanced heart failure and describes new diagnostic and treatment options for these patients. Recognizing the patient with advanced heart failure is critical to facilitate timely referral to advanced heart failure centres. Unplanned visits for heart failure decompensation, malignant arrhythmias, co-morbidities, and the 2016 ESC guidelines criteria for the diagnosis of heart failure with preserved ejection fraction are included in this updated definition. Standard treatment is, by definition, insufficient in these patients. Inotropic therapy may be used as a bridge strategy, but it is only a palliative measure when used on its own, because of the lack of outcomes data. Major progress has occurred with short-term mechanical circulatory support devices for immediate management of cardiogenic shock and long-term mechanical circulatory support for either a bridge to transplantation or as destination therapy. Heart transplantation remains the treatment of choice for patients without contraindications. Some patients will not be candidates for advanced heart failure therapies. For these patients, who are often elderly with multiple co-morbidities, management of advanced heart failure to reduce symptoms and improve quality of life should be emphasized. Robust evidence from prospective studies is lacking for most therapies for advanced heart failure. There is an urgent need to develop evidence-based treatment algorithms to prolong life when possible and in accordance with patient preferences, increase life quality, and reduce the burden of hospitalization in this vulnerable patient population.

Double organ transplantation in cardiac amyloidosis.

BACKGROUND: Cardiac amyloidosis, particularly primary or AL amyloidosis, is the most common infiltrative cardiomyopathy and is associated with a poor prognosis. The outcome of cardiac transplantation is generally poor, and almost half of patients die while waiting for the procedure to be done. PATIENT: We report here the remarkable case of a 63-year-old man with heart failure caused by AL amyloidosis. After a long course, which included rapid deterioration of preexisting heart failure, cardiac arrest, cardiogenic shock, biventricular assist device support, heart transplantation, renal failure, kidney transplantation and finally a life-threatening H1N1 virus pneumonia, the patient managed not only to survive but also to return fully to his previous demanding duties and lifestyle. DISCUSSION: Early use of left ventricular or biventricular mechanical circulatory support may be beneficial as a bridge to transplantation in patients with cardiac AL amyloidosis.

Intravascular Ultrasonic Imaging of Coronary Arterial Remodeling in Heart Transplant Recipients.

The purpose of this study was to evaluate long-term changes of transplant coronary arteries, including vessel, plaque, and lumen areas. There are limited long-term data on vessel remodeling after heart transplantation. We analyzed serial intravascular ultrasound images of the left anterior descending coronary artery (LAD) in 54 heart transplantation recipients. Nine patients (16.7%) had a history of rejection. Proximal left anterior descending artery segments were matched among time points, a ≥20-mm long segment was analyzed every 1 mm, and results were normalized for analysis length and reported as mm(3)/mm. During follow-up, vessel area decreased (-0.48 ± 1.3 mm(3)/mm/year), and plaque area did not change (-0.01 ± 0.47 mm(3)/mm/year). As a result, lumen area decreased (-0.52 ± 1.34 mm(3)/mm/year). The change in mean lumen area was well correlated to the change in mean vessel area (r = 0.94, p <0.01) but not to the change in mean plaque area (r = -0.27, p = 0.05). In conclusion, lumen loss occurred during long-term follow-up of patients who underwent heart transplantation, primarily secondary to negative remodeling (decrease in vessel dimensions).

Combined aerobic/inspiratory muscle training vs. aerobic training in patients with chronic heart failure: The Vent-HeFT trial: a European prospective multicentre randomized trial.

AIMS: Vent-HeFT is a multicentre randomized trial designed to investigate the potential additive benefits of inspiratory muscle training (IMT) on aerobic training (AT) in patients with chronic heart failure (CHF). METHODS AND RESULTS: Forty-three CHF patients with a mean age of 58 ± 12 years, peak oxygen consumption (peak VO2 ) 17.9 ± 5 mL/kg/min, and LVEF 29.5 ± 5% were randomized to an AT/IMT group (n = 21) or to an AT/SHAM group (n = 22) in a 12-week exercise programme. AT involved 45 min of ergometer training at 70-80% of maximum heart rate, three times a week for both groups. In the AT/IMT group, IMT was performed at 60% of sustained maximal inspiratory pressure (SPImax ) while in the AT/SHAM group it was performed at 10% of SPImax , using a computer biofeedback trainer for 30 min, three times a week. At baseline and at 3 months, patients were evaluated for exercise capacity, lung function, inspiratory muscle strength (PImax ) and work capacity (SPImax ), quality of life (QoL), LVEF and LV diameter, dyspnoea, C-reactive protein (CRP), and NT-proBNP. IMT resulted in a significantly higher benefit in SPImax (P = 0.02), QoL (P = 0.002), dyspnoea (P = 0.004), CRP (P = 0.03), and NT-proBNP (P = 0.004). In both AT/IMT and AT/SHAM groups PImax (P < 0.001, P = 0.02), peak VO2 (P = 0.008, P = 0.04), and LVEF (P = 0.005, P = 0.002) improved significantly; however, without an additional benefit for either of the groups. CONCLUSION: This randomized multicentre study demonstrates that IMT combined with aerobic training provides additional benefits in functional and serum biomarkers in patients with moderate CHF. These findings advocate for application of IMT in cardiac rehabilitation programmes.