Left ventricular volumes and function in successful and failed His-BundLe Pacing. A comparative prospective study.

INTRODUCTION: Initial data suggest that His Bundle Pacing (HBP) could preserve long-term cardiac structure and function better than Right Ventricular Pacing (RVP), but evidence is limited. METHODS: We studied consecutive patients with baseline ejection fraction (EF) ≥ 50% who underwent HBP attempt, either successful (HBP group) or failed (RVP group). Two-dimensional (2D) and three-dimensional (3D) echocardiography were carried out at baseline and after 6 months of ventricular pacing burden > 20%. RESULTS: Among 68 patients, 40 underwent successful HBP, and 28 RVP. The HBP and RVP groups did not differ for age, sex and pacing indication. At baseline, the HBP and RVP groups did not differ for 2D EF (62% vs. 62%), 3D EF (60% vs. 63%), 2D (-19% vs. -19%) and 3D global longitudinal strain (GLS) (-15% vs. -16%). After 6 months, 2D EF (-3.86%) and 3D EF (-5.71%) significantly decreased in the RVP group and did not change in the HBP group (p for interaction .006 and <.001, respectively). 2D GLS (3.08%) and 3D GLS (2.22%) significantly increased in the RVP group, but did not change in the HBP group (p for interaction .013 and <.016, respectively). Pacing induced cardiomyopathy (PICM) (EF drop ≥ 10% and EF < 50%) occurred in 14% (RVP) versus 0% (HBP) of patients (p = .025). CONCLUSIONS: Successful HBP was superior to RVP in preserving LV systolic function despite a high ventricular pacing burden, and was less frequently associated with PICM.

Therapy of Type 2 diabetes: more gliflozines and less metformin?

Metformin is a frequently used anti-diabetic drug. In addition to the well-known modulating properties on glyco-metabolic control, metformin reduces cardiovascular (CV) risk partly independently of its anti-hyperglycaemic effect. The use of 'new' anti-diabetic drugs, inhibitors of the renal Na-glucose co-transporter (SGLTs-I or 'gliflozines') and GLP-1 receptor agonists (GLP1-RAs), has further contributed to challenge the strictly 'gluco-centric' view of diabetic CV disease. Several controlled trials have demonstrated that the cardio-renal benefits of gliflozines and GLP1-RAs are present regardless of the presence of metformin as 'background' therapy. The impact on the 'cardio-renal continuum' exerted by SGLTs-I was also noted in non-diabetic patients with heart failure and reduced or preserved ventricular function and different levels of renal function. These drugs reduced re-hospitalization, CV mortality, and progression to end-stage renal disease. These clinical acquisitions, implemented by Scientific Societies, have led to a change in the therapeutic approach to diabetic cardio-renal disease. Although metformin still represents a valid therapeutic option to be offered particularly to 'naïve' diabetic patients without previous cardio-renal events, SGLTs-I and/or GLP1-RAs emerge as 'first-line' drugs in diabetic patients with previous CV events, or at high CV risk, without having to request 'on board' metformin therapy.

Soluble CD40 ligand and outcome in patients with coronary artery disease undergoing percutaneous coronary intervention.

OBJECTIVES: CD40 ligand (CD40L), a transmembrane glycoprotein belonging to the tumor necrosis factor family and expressed by a variety of cells, is involved in the basic mechanisms of inflammation, atherosclerosis and thrombosis. Some studies suggest that the soluble form of CD40L (sCD40L) is a predictor of major cardiovascular events and mortality in a variety of clinical settings, but data from literature are conflicting. METHODS: We studied consecutive patients with acute (ACS) or chronic (CCS) coronary syndrome who underwent percutaneous coronary artery intervention (PCI). Blood samples for sCD40L dosage were taken at baseline immediately before PCI. We tested the relation between sCD40L and pre-specified outcome measures consisting of new ACS, clinical restenosis and all-cause mortality. We recruited 3,841 patients (mean age 64 ± 11 years, 79% men) with ACS (n=2,383) or CCS (n=1,458). RESULTS: During a mean follow-up of two years (±0.6 years), 642 patients developed ACS, 409 developed restenosis (≥70% of at least one of the previously treated coronary segments) and 175 died. For each 1-standard deviation increase in sCD40L (0.80 ng/mL), the hazard ratios (HRs) for ACS, restenosis, and mortality were 1.11 (95% confidence interval [CI]: 1.05 to 1.18, p<0.0001), 1.10 (95% CI: 1.02 to 1.19, p=0.010), and 1.00 (95% CI: 0.86 to 1.16, p=0.983), respectively. In multivariable Cox regression models with adjustment for several potential confounders including age, acute or chronic coronary syndrome, multi-vessel disease, stent placement, diabetes, previous coronary events and dyslipidemia, sCD40L remained an independent predictor of ACS and coronary restenosis. There were no interactions between sCD40L and acute or chronic coronary syndrome or stent placement. CONCLUSIONS: Among patients with ACS or CCS who undergo PCI, higher levels of sCD40L predict an increased risk of acute coronary events and coronary restenosis, but not of mortality.

Association of statin pretreatment with presentation characteristics, infarct size and outcome in older patients with acute coronary syndrome: the Elderly ACS-2 trial.

BACKGROUND: prior statin treatment has been shown to have favourable effects on short- and long-term prognosis in patients with acute coronary syndrome (ACS). There are limited data in older patients. The aim of this study was to investigate the association of previous statin therapy and presentation characteristics, infarct size and clinical outcome in older patients, with or without atherosclerotic cardiovascular disease (ASCVD), included in the Elderly-ACS 2 trial. METHODS: data on statin use pre-admission were available for 1,192 of the 1,443 patients enrolled in the original trial. Of these, 531 (44.5%) were already taking statins. Patients were stratified based on established ASCVD and statin therapy. ACS was classified as non-ST elevation or ST elevation myocardial infarction (STEMI). Infarct size was measured by peak creatine kinase MB (CK-MB). All-cause death in-hospital and within 1 year were the major end points. RESULTS: there was a significantly lower frequency of STEMI in statin patients, in both ASCVD and No-ASCVD groups. Peak CK-MB levels were lower in statin users (10 versus 25 ng/ml, P < 0.0001). There was lower all-cause death in-hospital and within 1 year for subjects with ASCVD already on statins independent of other baseline variables. There were no differences in all-cause death for No-ASCVD patients whether or not on statins. CONCLUSIONS: statin pretreatment was associated with more favourable ACS presentation and lower myocardial damage in older ACS patients both ASCVD and No-ASCVD. The incidence of all-cause death (in-hospital and within 1 year) was significantly lower in the statin treated ASCVD patients.

The myocardial bridge: incidence, diagnosis, and prognosis of a pathology of uncertain clinical significance.

The myocardial bridge (MB) is a common anomaly of the coronary tree, very often clinically silent. The artery typically involved is the left anterior descending in its proximal and/or middle portion. MB can cause ischaemia with various mechanisms, directly proportional to the degree of compression of the intra-myocardial tract, which impairs the coronary flow. It is a dynamic phenomenon that is affected by the adrenergic tone and is therefore often brought by physical exercise. MB, when symptomatic, often begins with angina from exertion; some patients have more severe conditions such as unstable angina or myocardial infarction. Coronary vasospasm related to MB-induced endothelial dysfunction can explain a number of cases that come to observation even with catastrophic pictures such as ventricular fibrillation caused by ischaemia. The diagnostic workup includes the non-invasive study using computed tomography angiography and the invasive study of the haemodynamic impact using pressure and Doppler guides. In symptomatic cases, drug therapy with a beta-blocker is enough to manage angina. When it fails, there is the option of coronary angioplasty or surgical treatment techniques.

Procedural myocardial injury, infarction and mortality in patients undergoing elective PCI: a pooled analysis of patient-level data.

AIMS: The prognostic importance of cardiac procedural myocardial injury and myocardial infarction (MI) in chronic coronary syndrome (CCS) patients undergoing elective percutaneous coronary intervention (PCI) is still debated. METHODS AND RESULTS: We analysed individual data of 9081 patients undergoing elective PCI with normal pre-PCI baseline cardiac troponin (cTn) levels. Multivariate models evaluated the association between post-PCI elevations in cTn and 1-year mortality, while an interval analysis evaluated the impact of the size of the myocardial injury on mortality. Our analysis was performed in the overall population and also according to the type of cTn used [52.0% had high-sensitivity cTn (hs-cTn)]. Procedural myocardial injury, as defined by the Fourth Universal Definition of MI (UDMI) [post-PCI cTn elevation ≥1 × 99th percentile upper reference limit (URL)], occurred in 52.8% of patients and was not associated with 1-year mortality [adj odds ratio (OR), 1.35, 95% confidence interval (CI) (0.84-1.77), P = 0.21]. The association between post-PCI cTn elevation and 1-year mortality was significant starting ≥3 × 99th percentile URL. Major myocardial injury defined by post-PCI ≥5 × 99th percentile URL occurred in 18.2% of patients and was associated with a two-fold increase in the adjusted odds of 1-year mortality [2.29, 95% CI (1.32-3.97), P = 0.004]. In the subset of patients for whom periprocedural evidence of ischaemia was collected (n = 2316), Type 4a MI defined by the Fourth UDMI occurred in 12.7% of patients and was strongly associated with 1-year mortality [adj OR 3.21, 95% CI (1.42-7.27), P = 0.005]. We also present our results according to the type of troponin used (hs-cTn or conventional troponin). CONCLUSION: Our analysis has demonstrated that in CCS patients with normal baseline cTn levels, the post-PCI cTn elevation of ≥5 × 99th percentile URL used to define Type 4a MI is associated with 1-year mortality and could be used to detect 'major' procedural myocardial injury in the absence of procedural complications or evidence of new myocardial ischaemia.

Prognostically relevant periprocedural myocardial injury and infarction associated with percutaneous coronary interventions: a Consensus Document of the ESC Working Group on Cellular Biology of the Heart and European Association of Percutaneous Cardiovascular Interventions (EAPCI).

A substantial number of chronic coronary syndrome (CCS) patients undergoing percutaneous coronary intervention (PCI) experience periprocedural myocardial injury or infarction. Accurate diagnosis of these PCI-related complications is required to guide further management given that their occurrence may be associated with increased risk of major adverse cardiac events (MACE). Due to lack of scientific data, the cut-off thresholds of post-PCI cardiac troponin (cTn) elevation used for defining periprocedural myocardial injury and infarction, have been selected based on expert consensus opinions, and their prognostic relevance remains unclear. In this Consensus Document from the ESC Working Group on Cellular Biology of the Heart and European Association of Percutaneous Cardiovascular Interventions (EAPCI), we recommend, whenever possible, the measurement of baseline (pre-PCI) cTn and post-PCI cTn values in all CCS patients undergoing PCI. We confirm the prognostic relevance of the post-PCI cTn elevation >5× 99th percentile URL threshold used to define type 4a myocardial infarction (MI). In the absence of periprocedural angiographic flow-limiting complications or electrocardiogram (ECG) and imaging evidence of new myocardial ischaemia, we propose the same post-PCI cTn cut-off threshold (>5× 99th percentile URL) be used to define prognostically relevant 'major' periprocedural myocardial injury. As both type 4a MI and major periprocedural myocardial injury are strong independent predictors of all-cause mortality at 1 year post-PCI, they may be used as quality metrics and surrogate endpoints for clinical trials. Further research is needed to evaluate treatment strategies for reducing the risk of major periprocedural myocardial injury, type 4a MI, and MACE in CCS patients undergoing PCI.

Permanent His bundle pacing using a new tridimensional delivery sheath and a standard active fixation pacing lead: The telescopic technique.

INTRODUCTION: Permanent His bundle pacing (PHBP) preserves physiological ventricular activation but technical difficulties have limited its widespread use. We report the first experience of PHBP performed with a new specific delivery sheath (Selectra 3D, Biotronik, Berlin, Germany) and an extendable-retractable active screw, stylet-driven pacing lead (Solia S 60, Biotronik). METHODS AND RESULTS: Clinical, procedural, ECG, and electrical data from consecutive patients undergoing PHBP with this system were collected at implantation, and follow-up was performed after 1 month. Our cohort included 17 patients (71% males; mean age 76 ± 8 years) undergoing permanent pacing for sick sinus syndrome (59%) or atrioventricular block (41%). PHBP was successful in 15 (88%) procedures with mean procedure and fluoroscopy times of 63 ± 14 and 13 ± 5 min, respectively. The pacing threshold was 2.1 ± 1.1 V @1 ms and the sensed R-wave amplitude was 5.6 ± 3.5 mV; bipolar and unipolar pacing impedances were 526 ± 115 and 369 ± 109 Ω, respectively. At discharge, neither procedure-related complications nor lead dislodgement or pacing capture failures was reported. After 1 month, 14 (93%) patients still demonstrated His bundle stimulation and one (7%) lost His bundle capture but the lead revision was not necessary because the myocardial pacing threshold was stable. Follow-up threshold (2 ± 1.1 vs. 2.3 ± 1.2 V@1 ms, p = .239) and sensed R-wave amplitude (5.6 ± 3.4 vs. 6.4 ± 2.5, p = .403) was unchanged compared to the acute phase. CONCLUSION: PHBP performed with a standard active fixation pacing lead and a new delivery sheath for His pacing is feasible, safe and demonstrates clinically acceptable electric performance both at implantation and after 1 month.

The ISCHEMIA trial: optimal medical therapy against PTCA in the stable patient: the endless story.

In patients with acute coronary syndrome, an aggressive approach with coronary angiography and revascularization leads to important benefits compared to medical therapy alone. On the contrary, the prognostic impact of coronary revascularization in patients suffering from stable coronary artery disease has long been the subject of debate. The pivotal study in this area is COURAGE, published in 2007, in which coronary revascularization showed no benefit about the combined endpoint of death from all causes and acute myocardial infarction (AMI), compared to medical therapy. The ISCHEMIA study, published in 2020, compared selective coronary angiography and revascularization vs. a non-invasive approach. By protocol, the patients were initially evaluated with coronary computed axial tomography angiography: in case of coronary stenosis >50%, they were then randomized to the two strategies. While in the invasive arm patients were revascularized, in the non-invasive arm revascularization was used only in case of patient destabilization. As in COURAGE, the results of ISCHEMIA did not demonstrate superiority of revascularization over medical therapy alone for a combined endpoint of cardiovascular death, AMI, or hospitalization for unstable angina, heart failure, or cardiac arrest. Based on recent evidence from ISCHEMIA, it is therefore confirmed that coronary revascularization in stable patients does not seem to improve the prognosis compared to medical therapy alone.

Certainties fading away: ß-blockers do not worsen chronic obstructive pulmonary disease.

For many years, ß-blockers have been considered contraindicated in patients with heart failure (HF) and in those with bronchial asthma or even chronic obstructive pulmonary disease (COPD) although without clear evidence of asthma. Today, despite overwhelming evidence of the usefulness of ß-blockers, especially in HF with reduced left ventricular ejection fraction (HFrEF), and in ischaemic heart disease, some reluctance persists in using these drugs when COPD coexists. Such resistance is due to the fear that a possible worsening of bronchospasm induced by ß-blockers could induce negative effects greater than the benefits. The Guidelines of the European Society of Cardiology clearly suggest that: (i) implantation of a cardiac defibrillator (ICD) are not contraindicated in COPD without clear evidence of bronchial asthma; (ii) ß-blockers are only 'relatively' contraindicated when there is certainty of bronchial asthma with a documented bronchodilator response to the ß2 stimulant. Therefore, bronchial asthma is not an absolute contraindication to ß-blockers. The cardiologist should not limit the diagnosis of COPD to clinical suspicion, but should rely on a spirometry examination associated with any bronchodilation tests. In any case, selective ß1 blockers are preferred, starting at a basic dose, which ensure a better dilator response to bronchodilators and in any case cause less bronchospasm than non-selective ß-blockers. Unfortunately, there is still some reluctance to the use of ß-blockers in patients with COPD associated with HF, which should be eliminated.