Left bundle branch area versus conventional pacing after transcatheter valve implant for aortic stenosis: the LATVIA study.

BACKGROUND: Atrioventricular block (AVB) is a frequent complication in patients undergoing transcatheter aortic valve implantation (TAVI). Right apex ventricular pacing (RVP) represents the standard treatment but may induce cardiomyopathy over the long term. Left bundle branch area pacing (LBBAP) is a promising alternative, minimizing the risk of desynchrony. However, available evidence with LBBAP after TAVI is still low. OBJECTIVE: To assess the feasibility and safety of LBBAP for AVB post-TAVI compared with RVP. METHODS: Consecutive patients developing AVB early after TAVI were enrolled between 1 January 2022 and 31 December 2022 at three high-volume hospitals and received LBBAP or RVP. Data on procedure and at short-term follow-up (at least 3 months) were collected. RESULTS: A total of 38 patients (61% men, mean age 83 ±â€Š6 years) were included; 20 patients (53%) received LBBAP. Procedural success was obtained in all patients according to chosen pacing strategy. Electrical pacing performance at implant and after a mean follow-up of 4.2 ±â€Š2.8 months was clinically equivalent for both pacing modalities. In the LBBAP group, procedural time was longer (70 ±â€Š17 versus 58 ±â€Š15 min in the RVP group, P  = 0.02) and paced QRS was shorter (120 ±â€Š19 versus 155 ±â€Š12 ms at implant, P  < 0.001; 119 ±â€Š18 versus 157 ±â€Š9 ms at follow-up, P  < 0.001). Complication rates did not differ between the two groups. CONCLUSION: In patients with AVB after TAVI, LBBAP is feasible and safe, resulting in a narrow QRS duration, either acutely and during the follow-up, compared with RVP. Further studies are needed to evaluate if LBBAP reduces pacing-induced cardiomyopathy in this clinical setting.

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.

The pharmacology of anticoagulant drug treatment options in COVID-19 patients: reviewing real-world evidence in clinical practice.

INTRODUCTION: The optimal anticoagulation strategy for venous thromboembolism (VTE) prevention among COVID-19 patients, hospitalized or in the community setting, is still challenging and largely based on real-world evidence. AREAS COVERED: We analyzed real-world data regarding the safety and effectiveness of anticoagulant treatment, both parenteral and oral, for VTE prevention or atrial fibrillation (AF)/VTE treatment among COVID-19 patients. EXPERT OPINION: The efficacy of low-molecular-weight heparin (LMWH) doses for VTE prevention correlates with COVID-19 disease status. LMWH prophylactic dose may be useful in COVID-19 patients at the early stage of the disease. LMWH intermediate or therapeutic dose is recommended in COVID-19 patients with an advanced stage of the disease. COVID-19 patients on VKA therapy for atrial fibrillation (AF) and VTE should switch to NOACs in the community setting or LMWH in the hospital setting. No definitive data on de-novo starting of NOACs or VKA therapy for VTE prevention in COVID-19 outpatients are available. In patients at high risk discharged after hospitalization due to COVID-19, thromboprophylaxis with NOACs may be considered.

[On the Field of Honor. Historical research in memory of Italian male nurses who died in the First World War]. / Sul campo dell'Onore. Ricerca storica in memoria degli infermieri italiani caduti nella Prima Guerra Mondiale.

AIM: Several Italian male nurses employed at the Ospedale Maggiore in Milan were among the dead during First World War. This paper investigates whether and in which way these people are remembered. In addition the authors draw a picture of the nursing profession as it were in the early Twentieth Century in Italy. METHOD: The administrative documentation of 127 male nurses on duty at the Ospedale Maggiore in Milan and called to arms between 1915 and 1918 was examined. The documents were found in the historical archive of the Ospedale Maggiore from July 2015 to March 2016 and analyzed using the method of historical research according to Chabod (2012). RESULTS: Documents that witnessed the death of 5 male nurses during the war were found. These people were praised for their courage, self-sacrifice and commitment in attending the sick and the wounded. The hospital community arranged to devolve a sum of money to their families in sign of gratitude and commemorated them by engraving their names in a marble monument. CONCLUSIONS: Many memories of civilian male nurses in the years 1915-1918 emerged from this investigation, and the professional identity of nurses in the 1920s emerged quite clearly. The participation of male nurses in the First World War, in conjunction with the recurrence of its centenary, could be further deepened.

Atrial fibrillation and cardiac resynchronization therapy.

PURPOSE OF REVIEW: Atrial fibrillation and heart failure are commonly encountered in current clinical practice. This review aims to revisit the complex interaction of these two common situations and the best treatment whenever both occurs, especially focusing on heart failure patients undergoing cardiac resynchronization therapy (CRT). RECENT FINDINGS: It has been recently confirmed that in patients undergoing cardiac resynchronization therapy, 100% biventricular pacing percentage should be pursued. Large observational studies confirmed that atrioventricular junction ablation is very often the only way to gain 100% biventricular pacing in atrial fibrillation. SUMMARY: On the basis of the recent observational extensive data, in patients presenting intermediate or elevated atrial tachycardia-atrial fibrillation burden, atrioventricular junction ablation may represent a fundamental tool to achieve full CRT delivery, thus, conferring marked improvements in global cardiac function, and by extension, in survival. Atrial fibrillation patients should not be excluded from CRT, provided that maximal biventricular pacing is warranted.

The effects of gender on electrical therapies for the heart: procedural considerations, results and complications: A report from the XII Congress of the Italian Association on Arrhythmology and Cardiostimulation (AIAC).

Use of cardiac implantable devices and catheter ablation is steadily increasing in Western countries following the positive results of clinical trials. Despite the advances in scientific knowledge, tools development, and techniques improvement we still have some grey area in the field of electrical therapies for the heart. In particular, several reports highlighted differences both in medical behaviour and procedural outcomes between female and male candidates. Women are referred later for catheter ablation of supraventricular arrhythmias, especially atrial fibrillation, leading to suboptimal results. On the opposite females present greater response to cardiac resynchronization, while the benefit of implantable defibrillator in primary prevention seems to be less pronounced. Differences on aetiology, clinical profile, and development of myocardial scarring are the more plausible causes. This review will discuss all these aspects together with gender-related differences in terms of acute/late complications. We will also provide useful hints on plausible mechanisms and practical procedural aspects.

Multipoint Pacing versus conventional ICD in Patients with a Narrow QRS complex (MPP Narrow QRS trial): study protocol for a pilot randomized controlled trial.

BACKGROUND: Despite an intensive search for predictors of the response to cardiac resynchronization therapy (CRT), the QRS duration remains the simplest and most robust predictor of a positive response. QRS duration of ≥ 130 ms is considered to be a prerequisite for CRT; however, some studies have shown that CRT may also be effective in heart failure (HF) patients with a narrow QRS (<130 ms). Since CRT can now be performed by pacing the left ventricle from multiple vectors via a single quadripolar lead, it is possible that multipoint pacing (MPP) might be effective in HF patients with a narrow QRS. This article reports the design of the MPP Narrow QRS trial, a prospective, randomized, multicenter, controlled feasibility study to investigate the efficacy of MPP using two LV pacing vectors in patients with a narrow QRS complex (100-130 ms). METHODS: Fifty patients with a standard ICD indication will be enrolled and randomized (1:1) to either an MPP group or a Standard ICD group. All patients will undergo a low-dose dobutamine stress echo test and only those with contractile reserve will be included in the study and randomized. The primary endpoint will be the percentage of patients in each group that have reverse remodeling at 12 months, defined as a reduction in left ventricular end-systolic volume (LVESV) of >15% from the baseline. DISCUSSION: This feasibility study will determine whether MPP improves reverse remodeling, as compared with standard ICD, in HF patients who have a narrow QRS complex (100-130 ms). TRIAL REGISTRATION: ClinicalTrials.gov, NCT02402816 . Registered on 25 March 2015.

Identification of genetic markers for treatment success in heart failure patients: insight from cardiac resynchronization therapy.

BACKGROUND: Cardiac resynchronization therapy (CRT) can improve ventricular size, shape, and mass and reduce mitral regurgitation by reverse remodeling of the failing ventricle. About 30% of patients do not respond to this therapy for unknown reasons. In this study, we aimed at the identification and classification of CRT responder by the use of genetic variants and clinical parameters. METHODS AND RESULTS: Of 1421 CRT patients, 207 subjects were consecutively selected, and CRT responder and nonresponder were matched for their baseline parameters before CRT. Treatment success of CRT was defined as a decrease in left ventricular end-systolic volume >15% at follow-up echocardiography compared with left ventricular end-systolic volume at baseline. All other changes classified the patient as CRT nonresponder. A genetic association study was performed, which identified 4 genetic variants to be associated with the CRT responder phenotype at the allelic (P<0.035) and genotypic (P<0.031) level: rs3766031 (ATPIB1), rs5443 (GNB3), rs5522 (NR3C2), and rs7325635 (TNFSF11). Machine learning algorithms were used for the classification of CRT patients into responder and nonresponder status, including combinations of the identified genetic variants and clinical parameters. CONCLUSIONS: We demonstrated that rule induction algorithms can successfully be applied for the classification of heart failure patients in CRT responder and nonresponder status using clinical and genetic parameters. Our analysis included information on alleles and genotypes of 4 genetic loci, rs3766031 (ATPIB1), rs5443 (GNB3), rs5522 (NR3C2), and rs7325635 (TNFSF11), pathophysiologically associated with remodeling of the failing ventricle.

The importance of increased percentage of biventricular pacing to improve clinical outcomes in patients receiving cardiac resynchronization therapy.

PURPOSE OF REVIEW: To describe the growing evidence that a maximal biventricular pacing is needed to gain the maximal benefits from cardiac resynchronization therapy (CRT). RECENT FINDINGS: Even small gains in the biventricular (BIV) pacing percentage are clinically important both to prevent acute heart failure and, more importantly, to improve survival. SUMMARY: Every effort should be made in all patients receiving CRT to approach 100% BIV pacing by a correct device programming, a correct pharmacologic regimen and atrioventricular nodal ablation in atrial fibrillation patients.

Genetic variants of the renin-angiotensin-aldosterone system and reverse remodeling after cardiac resynchronization therapy.

BACKGROUND: Reverse remodeling (RR) after cardiac resynchronization therapy (CRT) is associated with favorable clinical outcomes in heart failure (HF). The renin-angiotensin-aldosterone system (RAAS) is involved in the remodeling process. METHODS AND RESULTS: We assessed the association between RR and 8 common RAAS gene variants, which were determined by TaqMan assays, in 156 outpatients with chronic HF. RR was defined as a >15% decrease in left ventricular end systolic volume (LVESV) at 9 (interquartile range 7-12) months after CRT. We matched 76 patients who did not show RR (RR-) to 80 RR+ control subjects by age, sex, HF etiology, New York Heart Association (NYHA) functional class and left ventricular ejection fraction (LVEF). The frequency of the minor allele of the NR3C2 gene (rs5522 C/T), encoding the mineralocorticoid receptor, was higher in RR- than in RR (24/126 vs 10/150; P value after false discovery rate correction: <.0193). Conversely, LVESV decreased significantly less after CRT in carriers of the NR3C2 minor C allele (P = .02). After adjustment for age, sex, NYHA functional class, previous myocardial infarction, atrial fibrillation, and LVEF, RR- remained independently associated with NR3C2 C allele carriage (odds ratio 3.093, 95% confidence interval 1.253-7.632). CONCLUSIONS: The association of RR- after CRT with a common polymorphism in the mineralocorticoid receptor gene involved in aldosterone signaling suggests a possible role for variants in RAAS genes in progressive LV function decline, despite apparently effective CRT.

The values of defibrillation testing at implantable cardioverter defibrillator implantation: 'and then there were none'.

PURPOSE OF REVIEW: Since its advent, implantable cardioverter defibrillator (ICD) intra-operative defibrillation testing (DFT) has been a standard practice to confirm its optimal configuration. However, due to advances in device and lead technology, which now facilitate successful device implantation, and due to growing number of ICD primary prevention patients, the need for DFT has recently been questioned. The purpose of this review is to summarize the pro and contra DFT arguments, according to benefits, risk and clinical relevance, trying to identify the candidates for whom DFT is really indicated. RECENT FINDINGS: There is an ongoing debate on the need for DFT at ICD implant due to significant DFT-related complications; recently, many electrophysiologists have chosen not to perform DFT in many cases. Recent literature findings document large differences of practice between different centres and countries. In particular, there has been major debate and concern over performing DFT in patients with heart failure, indicated for CRT-D implants (cardiac resynchronization therapy with defibrillator). SUMMARY: Due to the potential for serious complications during DFT and expanding primary prevention ICD candidates, we agree with the growing tendency not to routinely perform DFT at implant, as the risks may overweigh the benefits.

Resumption of sinus rhythm in patients with heart failure and permanent atrial fibrillation undergoing cardiac resynchronization therapy: a longitudinal observational study.

AIMS: To investigate the temporal patterns, predictors, and prognostic impact of spontaneous sinus rhythm resumption (SRR) of heart failure (HF) patients with permanent atrial fibrillation (AF) treated with cardiac resynchronization therapy (CRT). METHODS AND RESULTS: This multicentre, retrospective, longitudinal study analysed 330 consecutive HF patients with permanent AF treated with a CRT device (mean age 70 +/- 9 years, male 83%, ischaemic aetiology 44%, NYHA class III-IV 93%, mean QRS duration 167 +/- 40 ms, and mean ejection fraction 26 +/- 7%). Clinical, echocardiographic, and outcome data were collected during follow-up. Thirty-four patients experienced SRR after CRT (10.3%) at a median 4-month follow-up. The strongest independent predictors were end-diastolic diameter (EDD) [hazard ratios (HR) 4.03, 95% confidence intervals (95% CI) 1.43-11.36, P = 0.008], post-CRT QRS

Cardiac resynchronization therapy in heart failure patients with atrial fibrillation.

Cardiac resynchronization therapy (CRT) is an important device-based, non-pharmacological approach that has shown, in large randomized trials, to improve left ventricular (LV) function and reduce both morbidity and mortality rates in selected patients affected by advanced heart failure (HF): New York Heart Association (NYHA) functional class III-IV, reduced LV systolic function with an ejection fraction (EF) or=120 ms, on optimal medical therapy, and who were in sinus rhythm. For the first time, the latest ESC and AHA/ACC/HRS Guidelines have considered atrial fibrillation (AF) patients, who constitute an important subgroup of HF patients, as eligible to receive CRT. Nevertheless, these Guidelines did not include a strategy for defining differentiated approaches according to AF duration or burden. In this review, the authors explain in which way AF may interfere with adequate CRT delivery, how to manage different AF burden, and finally present a brief overview on the effects of CRT in AF patients.

Insulin-treated type 2 diabetes is associated with a decreased survival in heart failure patients after cardiac resynchronization therapy.

BACKGROUND: Cardiac resynchronization therapy (CRT) improves cardiac performance and survival in patients with congestive heart failure. Recent observations suggest that diabetes is associated with a worse outcome in these patients. The aim of the study was to investigate the effect of diabetes and insulin treatment on outcome after CRT. METHODS: Diabetic status and insulin treatment were assessed in 447 patients who underwent CRT (males 80.8%, mean age 65.7 +/- 9.7 years, ejection fraction 29.9 +/- 6.11%). Patients were stratified in three groups according to the presence or absence of diabetes and insulin treatment. RESULTS: Nondiabetic patients were 366 (79.6%), noninsulin-treated diabetic patients 62 (13.9%), insulin-treated diabetic patients 29 (6.5%). The estimated death rate was 5.15 per 100 patients-year in the nondiabetic group, 8.63 in noninsulin-treated diabetics (HR 1.59, P = 0.240), and 15.84 in insulin-treated diabetics (HR 3.05, P = 0.004). Cardiac mortality accounted for 81% of deaths in nondiabetic patients and for 56% of deaths in diabetic patients. Diabetic patients tended to have a worse recovery of left ventricular ejection fraction over time (P = 0.057) and of the distance at 6-minute walking test (6MWT) (P = 0.018). CONCLUSIONS: Insulin-treated diabetes is associated with a worse functional recovery and a higher mortality in patients with advanced heart failure after CRT. While cardiac death accounts for the majority of deaths in nondiabetic patients, a relevant proportion of the mortality in diabetic patients seem to result from noncardiac causes.

Remission of left ventricular systolic dysfunction and of heart failure symptoms after cardiac resynchronization therapy: temporal pattern and clinical predictors.

BACKGROUND: The aim of the study was to determine whether cardiac resynchronization therapy (CRT) may induce a heart failure (HF) remission phase (recovery to New York Heart Association functional class I-II and regression of left ventricular [LV] dysfunction: LV ejection fraction [EF] > or = 50%) and to define the incidence and predictors of such a process. METHODS: Cardiac resynchronization therapy devices were successfully implanted in 520 consecutive HF patients from 1999 to 2006 (mean age 66 years, 82% male sex, New York Heart Association class > or = II, LVEF 28%, QRS 164 milliseconds, 6-minute hall walk distance 302 m) at our institution. Follow-up data were prospectively collected every 3 to 6 months. Continuous variables were stratified in tertiles. RESULTS: Over a median follow-up of 28 months, 26% of patients achieved LV remission (rate: 16 per 100 person-years). At univariate analysis, female sex (P = .032), non-coronary artery disease (CAD) etiology (P < .001), mitral regurgitation < 2/4 (P = .022), higher EF tertile (P < .001), lower diameter and volume tertiles (both P < .001), previous conventional right ventricle pacing (P = .029), and post-CRT-paced QRS (P = .008) predicted remission. At multivariate analysis, non-CAD etiology, LVEF 30% to 35%, and LV end-diastolic volume < 180 mL were strongly associated with HF remission phase (all P < .001). Concomitance of these 3 factors yielded a significantly higher remission rate compared with either no or only 1 factor (respectively, 60 vs 7 and 11 per 100 person-years, P < .001). CONCLUSIONS: Cardiac resynchronization therapy induces HF remission phase in 26% of patients, even after 3 years. Non-CAD etiology and moderately compromised LV function at baseline may easily predict this process.

Three years of cardiac resynchronization therapy: could superior benefits be obtained in patients with heart failure and narrow QRS?

AIM OF THE STUDY: To examine the long-term effects of cardiac resynchronization therapy (CRT) in patients presenting with heart failure (HF) and QRS 120 ms in the remaining 331 patients. The baseline characteristics of the 2 groups were similar. We evaluated indices of cardiac function, percentage of responders, and survival rates over a mean 28-month follow-up. RESULTS: Both groups experienced similar long-term increases in 6-MHW, and decreases in New York Heart Association functional class and LV end-systolic volume (all comparisons P < 0.0001 in both groups). Time interaction of changes in LVEF and percentage of responders were significantly different (P = 0.03 and P = 0.004, respectively), in favor of the narrow QRS group, where the changes were sustained and persisted at 2 and 3 years. The long-term death rate from HF was lower in the group with narrow than in the group with wide QRS complex (P = 0.04; log-rank test). CONCLUSIONS: CRT confers considerable long-term clinical, functional, and survival benefits in patients presenting with HF and narrow QRS, not preselected by echocardiographic criteria of dyssynchrony. Caution is advised before denying CRT to these patients on the basis of QRS width only.