Real-world data of patients affected by advanced heart failure treated with implantable cardioverter defibrillator and left ventricular assist device: Results of a multicenter observational study.

BACKGROUND: Left ventricular assist device (L-VAD) implantation is increasingly used in patients with heart failure (HF) and most patients also have an implantable cardioverter defibrillator (ICD). Limited data are available on the incidence of ICD therapies and complications in this special setting. The aim of this study was to analyze the real-world incidence and predictors of ICD therapies, complications and interactions between ICD and L-VAD. METHODS: We conducted a multicenter retrospective observational study in patients with advanced HF implanted with ICD and a continuous-flow L-VAD, followed-up in five advanced HF centers in Northern Italy. RESULTS: A total of 234 patients (89.7% male, median age 59, 48.3% with ischemic etiology) were enrolled. After a median follow-up of 21 months, 66 patients (28.2%) experienced an appropriate ICD therapy, 22 patients (9.4%) an inappropriate ICD therapy, and 17 patients (7.3%) suffered from an interaction between ICD and L-VAD. The composite outcome of all ICD-related complications was reported in 41 patients (17.5%), and 121 (51.7%) experienced an L-VAD-related complication. At multivariable analysis, an active ventricular tachycardia (VT) zone and a prior ICD generator replacement were independent predictors of ICD therapies and of total ICD-related complications, respectively. CONCLUSIONS: Real-world patients with both L-VAD and ICD experience a high rate of ICD therapies and complications. Our findings suggest the importance of tailoring device programming in order to minimize the incidence of unnecessary ICD therapies, thus sparing the need for ICD generator replacement, a procedure associated to a high risk of complications.

Atrial arrhythmias and heart failure: A "modern view" of an old paradox.

BACKGROUND: Heart failure (HF) and atrial arrhythmias (AAs) are two clinical conditions that characterize the daily clinical practice of cardiologists. In this perspective review, we analyze the shared etiopathogenetic pathways of atrial arrhythmias, which are the most common cause of atrial arrhythmias-induced cardiomyopathy (AACM) and HF. HYPOTHESIS: The aim is to explore the pathophysiology of these two conditions considering them as a "unicum", allowing the definition of a cardiovascular continuum where it is possible to predict the factors and to identify the patient phenotype most at risk to develop HF due to atrial arrhythmias. METHODS: Potentially eligible articles, identified from the Electronic database (PubMed), and related references were used for a literature search that was conducted between January 2022 and January 2023. Search strategies were designed to identify articles that reported atrial arrhythmias in association with heart failure and vice versa. For the search we used the following keywords: atrial arrhythmias, atrial fibrillation, heart failure, arrhythmia-induced cardiomyopathy, tachycardiomyopathy. We identified 620 articles through the electronic database search. Out of the 620 total articles we removed 320 duplicates, thus selecting 300 eligible articles. About 150 titles/abstracts were excluded for the following reasons: no original available data, no mention of atrial arrhythmias and heart failure crosstalk, very low quality analysis or evidence. We excluded also non-English articles. When multiple articles were published on the same topic, the articles with the most complete set of data were considered. We preferentially included all papers that could provide the best evidence in the field. As a result, the present review article is based on a final number of 104 references. RESULTS: While the pathophysiology of AACM and Heart Failure with reduced ejection fraction (HFrEF) has been studied in detail over the years, the causal link between atrial arrhythmias and heart failure with Preserved Ejection Fraction (HFpEF) has been often subject of interest. HFpEF is strictly related to AAs, which has always been considered significant risk factor. In this review we described the pathophysiological links between atrial fibrillation and heart failure. Furthermore, we illustrated and discussed the preclinical and clinical predicting factors of AF and HFpEF, and the corresponding targets of the available therapeutic agents. Finally, we outlined the patient phenotype at risk of developing AF and HFpEF (Central Illustration). CONCLUSIONS: In this review, we underline how these two clinical conditions (AF and HFpEF) represent a "unicum" and, therefore, should be considered as a single disease that can manifest itself in the same phenotype of patients but at different times. Furthermore, considering that today we have few therapeutic strategies to treat these patients, it would be good to make an early diagnosis in the initial stages of the disease or intervene even before the development of signs and symptoms of HF. This is possible only by paying greater attention to patients with predisposing factors and carrying out a targeted screening with the correct diagnostic methods. A systemic approach aimed at improving the immuno-metabolic profile of these patients by lowering the body mass index, threatening the predisposing factors, lowering the mean heart rate and reducing the sympathetic nervous system activation is the key strategy to reduce the clinical impact of this disease.

Prognostic value of tricuspid regurgitation.

Tricuspid regurgitation (TR) has a considerable prevalence in the overall population, that further increases in selected categories of patients. Three morphologic types of TR prevail, namely primary, secondary and atrial TR, mostly, but not always, occurring in different subsets of patients. Recent evidences demonstrate a negative impact of TR on outcomes, irrespective of etiology and even when less than severe in grading. Unfortunately, current surgical standards are void of strong prospective evidence of positive impact on clinical outcomes. While on one hand recent advances in diagnosis and risk stratification of patients with TR are shedding light onto the population that may benefit from intervention and its appropriate timing, on the other hand the arrival on stage of percutaneous treatment options is widening even more the therapeutic options for such population. In this review we will address and discuss the available evidence on the prognostic impact of TR in different clinical contexts encountered in practice.

Percutaneous Tricuspid Valve Repair.

Tricuspid regurgitation (TR) negatively affects patient outcomes. Surgical tricuspid valve repair/replacement carries a high operative risk and is not a viable option for many high-risk patients. Percutaneous approaches provide an attractive alternative solution for such patients since they represent a valid alternative to open heart surgery without the significant risks carried by surgery. A number of percutaneous devices are currently under clinical development. This review will discuss about the latest development in the field of percutaneous tricuspid valve repair with possible future developments.

Digoxin-specific Fab and therapeutic plasma exchange for digitalis intoxication and renal failure.

Treatment of chronic digitalis intoxication includes suspension of drug intake, which may be sufficient in case of mild manifestations, and supportive measures. Severe bradycardia requires the administration of atropine or isoproterenol; placement of a temporary pacemaker may be required in case of absent response to pharmacological therapy. Severe and life-threatening manifestations should be treated with digoxin-specific fragment antigen binding antibodies (Fab). Therapeutic plasma exchange has been suggested, in addition to Fab therapy, to maximize the clearance of Fab-digoxin complexes in patients with renal failure. To date, few case reports have described the use of such a therapeutic approach; currently, extracorporeal methods are not recommended as part of the treatment of digitalis intoxication, and stronger evidence is required to establish their benefit.

Transitory effusive-constrictive pericarditis.

Pericardial effusion of various sizes is a quite common clinical finding, while its progression to effusive-constrictive pericarditis occurs in about 1.4-14% of cases. Although available evidence on prevalence and prognosis of this rare pericardial syndrome is poor, apparently a considerable proportion of patients conservatively managed has a spontaneous resolution after several weeks. A 61-year-old female presented to our emergency department reporting fatigue, effort dyspnea and abdominal swelling. The echocardiography showed large pericardial effusion with initial hemodynamic impact, so she underwent a pericardiocentesis with drainage of 800-850cm3 of exudative fluid, on which diagnostic investigations were undertaken: possible viral and bacterial infections, medical conditions, iatrogenic causes, neoplastic and connective tissue diseases were all excluded. Despite empirical therapy with NSAIDs and colchicine, after about one week she had a recurrence of pericardial effusion and progressive development of constriction. Echocardiography performed after a few weeks of anti-inflammatory therapy showed resolution of constriction and PE, with clinical improvement. If progression of pericardial syndromes to a constrictive form is rarely described in literature, cases of transitory effusive-constrictive phase are even more uncommon, mainly reported during the evolution of pericardial effusion. According to the available data, risk of progression to a constrictive form is very low in case of idiopathic pericardial effusion. We report a case of large idiopathic subacute pericardial effusion, treated with pericardiocentesis and then evolved into an effusive-constrictive pericarditis. A prolonged anti-inflammatory treatment leads to complete resolution of pericardial syndrome without necessity of pericardiectomy.

Diuretic Combination Therapy in Acute Heart Failure: An Updated Review.

Loop diuretics are the cornerstone of decongestive therapy in patients presenting with acute heart failure and have been extensively studied in randomized clinical trials. Therefore, in current guidelines, they are the only drug with a class I recommendation to treat signs and symptoms of congestion when present. However, the percentage of patients achieving successful decongestion is suboptimal, and diuretic resistance frequently develops. Patients with a poor response to loop diuretics and those discharged with residual signs of congestion are characterized by a worse prognosis over time. Recently, a renovated interest in different diuretic classes sprouted among heart failure researchers in order to improve decongestion strategies and ameliorate short- and long-term clinical outcomes. Randomized clinical trials investigating associations among diuretic classes and loop diuretics have been performed but yielded variable results. Therefore, despite initial evidence of a possible benefit from some of these compounds, a definite way to approach diuretic resistance via diuretic combination therapy is still missing. The aim of this review is to summarize current clinical evidence on the use of diuretic combination therapy in patients with acute heart failure and to suggest a possible approach to avoid or counteract diuretic resistance.

Leadless Pacemaker Implantation Across Percutaneous Tricuspid Valve Prothesis Implanted Via Valve-in-Valve Technique.

We present the case of an 82-year-old woman with history of bivalvular replacement (mitral mechanical prothesis and tricuspid bioprothesis) and subsequent tricuspid percutaneous valve-in-valve bioprothesis implantation. The patient developed an indication for pacemaker implantation. We describe the feasibility of leadless pacemaker implantation across the tricuspid prothesis when all other techniques fail.

Bridging the gap in the symptomatic heart failure patient journey: insights from the Italian scenario.

BACKGROUND: The prognosis for heart failure (HF) patients remains poor, with a high mortality rate, and a marked reduction in quality of life (QOL) and functional status. This study aims to explore the ongoing needs of HF management and the epidemiology of patients followed by Italian HF clinics, with a specific focus on cardiac contractility modulation (CCM). RESEARCH DESIGN AND METHODS: Data from patients admitted to 14 HF outpatients clinics over 4 weeks were collected and compared to the results of a survey open to physicians involved in HF management operating in Italian centers. RESULTS: One hundred and five physicians took part in the survey. Despite 94% of patients receive a regular follow-up every 3-6 months, available therapies are considered insufficient in 30% of cases. Physicians reported a lack of treatment options for 23% of symptomatic patients with reduced ejection fraction (EF) and for 66% of those without reduced EF. Approximately 3% of HF population (two patients per month per HF clinic) meets the criteria for immediate CCM treatment, which is considered a useful option by 15% of survey respondents. CONCLUSIONS: Despite this relatively small percentage, considering total HF population, CCM could potentially benefit numerous HF patients, particularly the elderly, by reducing hospitalizations, improving functional capacity and QOL.

Mitral regurgitation in heart failure: insights from CPET combined with exercise echocardiography.

AIMS: In heart failure patients with reduced ejection fraction (HFrEF), exercise-induced functional mitral regurgitation (MR) may affect functional capacity and outcome. We sought to study functional and cardiac phenotypes of HFrEF patients according to the MR degree. METHODS AND RESULTS: We performed rest and exercise echocardiography (Ex-Echo), simultaneously combined with cardiopulmonary exercise test (CPET), in 102 HFrEF patients, identifying 3 groups: non-severe (ERO <20 mm2) MR (group A), exercise-induced severe (ERO ≥20 mm2) MR (group B), and rest severe MR (group C). Patients were tracked for the composite end point of death and heart failure hospitalization. Group B (ERO: rest= 14 ± 5 mm2, Ex= 28 ± 6 mm2; P = < 0.001) had a functional impairment (workload = 56 ± 21 vs. 50 ± 17 watts, P = 0.42; peak VO2 = 11.8 ± 3.2 vs. 11.5 ± 3.0 mL/Kg/min, P = 0.70) similar to Group C (ERO: rest = 29 ± 7 mm2, Ex = 42 ± 7 mm2, P = < 0.001), associated with comparable advanced left ventricle remodelling (end diastolic indexed volume = 107 ± 34 vs. 115 ± 30 mL/m2, P = 0.27), characterized by exercise-induced pulmonary hypertension (PH) (Ex systolic pulmonary pressures = 63 ± 16 mmHg). Group C showed the worse cardiac phenotype (right ventricle dilatation, dysfunction, and rest PH) with severe ventilatory impairment (VE/VCO2 = 41.2 ± 11) compared with Groups A and B. Moreover, Group C had the higher rate of death and HF hospitalization. CONCLUSIONS: In HFrEF patients, severe dynamic MR produces functional limitation similar to rest severe MR, characterized by dynamic PH. Rest severe MR reflects the most advanced bi-ventricular remodelling associated with rest PH, the most unfavourable ventilatory profile, and the worst mid-term outcome.

Right Ventricular Contractile Reserve and Pulmonary Circulation Uncoupling During Exercise Challenge in Heart Failure: Pathophysiology and Clinical Phenotypes.

OBJECTIVES: Right ventricular (RV) exercise contractile reserve (RVECR), its phenotypes, and its functional correlates are among the unresolved issues with regard to the role of the right ventricle in heart failure (HF) syndrome, and understanding these issues constitutes the objective of this study. BACKGROUND: Although the role of the right ventricle in HF syndrome might be fundamental, the pathophysiology of the failing right ventricle has not been extensively investigated. METHODS: Ninety-seven patients with HF (mean age 64 years, 70% men, mean left ventricular ejection fraction 33 ± 10%) underwent maximal exercise stress echocardiographic and cardiopulmonary exercise testing. RVECR and RV-to-pulmonary circulation (PC) coupling were assessed using the length-force relationship (tricuspid annular plane systolic excursion [TAPSE] vs. pulmonary artery systolic pressure) and the slope of mean pulmonary artery pressure versus cardiac output. On the basis of TAPSE, patients were categorized into 3 groups: those with TAPSE at rest ≥16 mm (group A, n = 60) and those with TAPSE at rest <16 mm, who were divided according to median TAPSE at peak exercise (15.5 mm) into 2 subgroups (group B, ≥15.5 mm, n = 19; group C, <15.5 mm, n = 18). RESULTS: Although they had similar left ventricular ejection fractions and rest RV impairment, compared with patients in group C, those in group B showed some degree of RVECR (upward shift of the length-force relationship), better RV-to-PC coupling (lower mean pulmonary artery pressure vs. cardiac output slope), and greater ventilatory efficiency (lower slope of minute ventilation to carbon dioxide output). Rest mitral regurgitation and net changes in pulmonary artery systolic pressure were the variables retained in the best regression model as correlates of RVECR. CONCLUSIONS: In patients with HF, RVECR unmasks different phenotypes. Impaired RV function at rest might not invariably lead to unfavorable RVECR and exercise RV-to-PC coupling. Testing these variables appears useful even in more advanced stages of HF to define various clinical conditions and, most likely, to define different levels of risk.

Prevalence and characterization of exercise oscillatory ventilation in apparently healthy individuals at variable risk for cardiovascular disease: A subanalysis of the EURO-EX trial.

INTRODUCTION: There has been a greater appreciation of several variables obtained by cardiopulmonary exercise testing (CPX). Exercise oscillatory ventilation (EOV) is a CPX pattern that has gained recognition as an ominous marker of poor prognosis in cardiac patients. The purpose of the present study is to characterize whether such an abnormal ventilatory pattern may also be detected in apparently healthy subjects and determine its clinical significance. METHODS: The study involved 510 subjects (mean age 60 ± 14 years; 49% male) with a broad cardiovascular (CV) risk factor profile who underwent CPX. RESULTS: The population was divided into two groups according to the presence (17%) or absence of EOV. Subjects with EOV were significantly older and a higher percentage was female. Risk factor profile and medication use was significantly different between subgroups, indicating subjects with EOV had a worse CV risk factor profile and were prescribed CV-focused preventive medications at a significantly higher frequency. Subjects with EOV had comparatively poorer CPX performance and gas exchange phenotype. Multivariate binary logistic regression analysis found being female was the strongest predictor of EOV (odds ratio: 2.77, 95% confidence interval (CI): 1.66-4.61, p < 0.001). A diagnosis of diabetes (odds ratio: 2.40, 95% CI: 1.34-4.15.2, p < 0.001) added significant value for predicting EOV and was retained in the regression. The likelihood for EOV for subjects who were female and diagnosed with diabetes was 3.71 (95% CI 1.88-7.30, p < 0.001). CONCLUSIONS: This is the first study to examine EOV prevalence and characterization in apparently healthy persons with results supporting an in-depth definition of abnormal exercise phenotypes.

Role of right ventricle and dynamic pulmonary hypertension on determining ΔVO2/ΔWork Rate flattening: insights from cardiopulmonary exercise test combined with exercise echocardiography.

BACKGROUND: Several cardiovascular diseases are characterized by an impaired O2 kinetic during exercise. The lack of a linear increase of Δoxygen consumption (VO2)/ΔWork Rate (WR) relationship, as assessed by expired gas analysis, is considered an indicator of abnormal cardiovascular efficiency. We aimed at describing the frequency of ΔVO2/ΔWR flattening in a symptomatic population of cardiac patients, characterizing its functional profile, and testing the hypothesis that dynamic pulmonary hypertension and right ventricular contractile reserve play a major role as cardiac determinants. METHODS AND RESULTS: We studied 136 patients, with different cardiovascular diseases, referred for exertional dyspnoea. Cardiopulmonary exercise test combined with simultaneous exercise echocardiography was performed using a symptom-limited protocol. ΔVO2/ΔWR flattening was observed in 36 patients (group A, 26.5% of population) and was associated with a globally worse functional profile (reduced peak VO2, anaerobic threshold, O2 pulse, impaired VE/VCO2). At univariate analysis, exercise ejection fraction, exercise mitral regurgitation, rest and exercise tricuspid annular plane systolic excursion, exercise systolic pulmonary artery pressure, and exercise cardiac output were all significantly (P<0.05) impaired in group A. The multivariate analysis identified exercise systolic pulmonary artery pressure (odds ratio, 1.06; confidence interval, 1.01-1.11; P=0.01) and exercise tricuspid annular plane systolic excursion (odds ratio, 0.88; confidence interval, 0.80-0.97; P=0.01) as main cardiac determinants of ΔVO2/ΔWR flattening; female sex was strongly associated (odds ratio, 6.10; confidence interval, 2.11-17.7; P<0.01). CONCLUSIONS: In patients symptomatic for dyspnea, the occurrence of ΔVO2/ΔWR flattening reflects a significantly impaired functional phenotype whose main cardiac determinants are the excessive systolic pulmonary artery pressure increase and the reduced peak right ventricular longitudinal systolic function.