Long- and short-term outcomes after transvenous lead extraction in a large single-centre patient cohort using the clinical frailty scale as a risk assessment tool.

BACKGROUND AND AIMS: The rate of cardiac implantable electronic device (CIED) implantations and the need for transvenous lead extraction (TLE) are growing worldwide. This study examined a large Swedish cohort with the aim of identifying possible predictors of post-TLE mortality with special focus on systemic infection patients and frailty. METHODS: This was a single centre study. Records of patients undergoing TLE between 2010 and 2018 were analysed. Statistical analyses were conducted to compare baseline characteristics of patients with different indications and identify risk factors of 30-day and 1-year mortality. RESULTS: A total of 893 patients were identified. Local infection was the dominant indication and pacemaker was the most common CIED. The mean age was 65 ± 16 years, 73 % were male and median follow-up was 3.9 years. Heart failure was the most common comorbidity. Patients with systemic infection were significantly older, frailer and had significantly higher levels of comorbidities. 30-day mortality and 1-year mortality rates were 2.5 % and 9.9 %, respectively. Systemic infection and chronic kidney disease (CKD) were independently associated with 30-day and 1-year mortality. Clinical frailty scale (CFS) 5-7 correlated independently with 1-year mortality in the entire cohort and specifically in systemic infection patients. CKD, cardiac resynchronization therapy and CFS 5-7 were significant risk factors for long-term mortality (death >1 year after TLE) in multivariable analysis. CONCLUSIONS: Systemic infection, kidney failure in addition to the novel parameter of frailty were associated with post-TLE all-cause mortality. These risk factors should be considered during pre-procedure risk stratification to improve post-TLE outcomes.

Endocardial pacing compared to epicardial left ventricle pacing and right ventricle pacing: A single-center long-term experience in a pediatric population.

BACKGROUND AND AIMS: Pediatric pacing is usually performed as epicardial pacing in small children in need of pacemaker therapy. Epicardial pacing compared with transvenous pacing for pediatric complete atrioventricular block (CAVB) has different strengths and weaknesses. The epicardial left ventricular wall position of the lead has been considered superior, in terms of contraction pattern, compared to a transvenous right ventricular stimulation. We aimed to compare QRS duration and cardiac function before and after the switch from epicardial to transvenous pacing in a pediatric population. METHODS: Pediatric patients with congenital or acquired CAVB, who underwent a switch from epicardial-to transvenous pacing at our center from 2005 to 2021, were identified through the national ICD- and Pacemaker Registry. Data regarding clinical status, ECG, and echocardiography before and after the switch and at last follow-up were collected. RESULTS: We included 15 children. The median age at the switch was 6.7 (4.4-11.7) years with a median weight of 21 (15-39) Kg. The median QRS duration with the transvenous systems was 136 (128-152) ms vs. a QRS duration during epicardial stimulation of 150 (144-170) ms with a median difference in QRS duration of 14 (6-20) ms. Children with a post-surgical AV block had a broader QRS duration, both with epicardial and endocardial stimulation. Before the switch, there was one patient with impaired left ventricular function (LVF) but with normal left ventricular end-diastolic diameters. After the switch, one patient developed symptomatic LV dysfunction with the recovery of LVF at the last follow-up after being implanted with a cardiac resynchronization therapy device. CONCLUSIONS: Our report of pediatric patients after switching from epicardial to transvenous pacing shows how transvenous pacing is not inferior to epicardial pacing in terms of QRS duration and no significant deterioration of cardiac function was detectable.

Left ventricular ejection fraction digit bias and reclassification of heart failure with mildly reduced vs reduced ejection fraction based on the 2021 definition and classification of heart failure.

AIMS: Aims were to evaluate (1) reclassification of patients from heart failure with mildly reduced (HFmrEF) to reduced (HFrEF) ejection fraction when an EF = 40% was considered as HFrEF, (2) role of EF digit bias, ie, EF reporting favouring 5% increments; (3) outcomes in relation to missing and biased EF reports, in a large multinational HF registry. METHODS AND RESULTS: Of 25,154 patients in the European Society of Cardiology (ESC) HF Long-Term registry, 17% had missing EF and of those with available EF, 24% had HFpEF (EF≥50%), 21% HFmrEF (40%-49%) and 55% HFrEF (<40%) according to the 2016 ESC guidelines´ classification. EF was "exactly" 40% in 7%, leading to reclassifying 34% of the HFmrEF population defined as EF = 40% to 49% to HFrEF when applying the 2021 ESC Guidelines classification (14% had HFmrEF as EF = 41% to 49% and 62% had HFrEF as EF≤40%). EF was reported as a value ending with 0 or 5 in ∼37% of the population. Such potential digit bias was associated with more missing values for other characteristics and higher risk of all-cause death and HF hospitalization. Patients with missing EF had higher risk of all-cause and CV mortality, and HF hospitalization compared to those with recorded EF. CONCLUSIONS: Many patients had reported EF = 40%. This led to substantial reclassification of EF from old HFmrEF (40%-49%) to new HFrEF (≤40%). There was considerable digit bias in EF reporting and missing EF reporting, which appeared to occur not at random and may reflect less rigorous overall care and worse outcomes.

Prognosis of CRT-treated and CRT-untreated unselected population with LBBB in Stockholm County.

AIMS: Left bundle branch block (LBBB) might be the first finding of cardiovascular diseases but also the prerequisite for cardiac resynchronization therapy (CRT) in heart failure (HF) with reduced ejection fraction (HFrEF). The prognosis for patients with LBBB and the implications of CRT in an unselected real-world setting are the focus of our study. METHODS AND RESULTS: A central electrocardiogram (ECG) database and national registers have been screened to identify patients with LBBB. Predictors of HF and the use of CRT were identified with Cox models. The hazard ratios (HRs) of death, cardiovascular death (CVD), and HF hospitalization (HFH) were estimated according to CRT use. Of 5359 patients with LBBB and QRS > 150 ms, median age 76 years, 36% were female. At the time of index ECG, 41% had a previous history of HF and 27% developed HF. Among 1053 patients with a class I indication for CRT, only 60% received CRT with a median delay of 137 days, and it was associated with a lower risk of death [HR: 0.45, 95% confidence interval (CI): 0.36-0.57], CVD (HR: 0.47, 95% CI: 0.35-0.63), and HFH (HR: 0.56, 95% CI: 0.48-0.66). The age of over 75 years and the diagnosis of dementia and chronic obstructive pulmonary disease were predictors of CRT non-use, while having a pacing/defibrillator device independently predicted CRT use. CONCLUSION: In an unselected LBBB population, CRT is underused but of great value for HF patients. Therefore, it is crucial to find ways of better implementing and understanding CRT utilization and characteristics that influence the management of our patients.

What determines who gets cardiac resynchronization therapy in Europe? A comparison between ESC-HF-LT registry, SwedeHF registry, and ESC-CRT Survey II.

AIMS: Cardiac resynchronization therapy (CRT) is effective in heart failure with reduced ejection fraction (HFrEF) and dyssynchrony but is underutilized. In a cohort study, we identified clinical, organizational, and level of care factors linked to CRT implantation. METHODS AND RESULTS: We included HFrEF patients fulfilling study criteria in the ESC-HF-Long Term Registry (ESC-HF-LT, n = 1031), the Swedish Heart Failure Registry (SwedeHF) (n = 5008), and the ESC-CRT Survey II (n = 11 088). In ESC-HF-LT, 36% had a CRT indication of which 47% had CRT, 53% had indication but no CRT, and the remaining 54% had no indication and no CRT. In SwedeHF, these percentages were 30, 25, 75, and 70%. Median age of patients with CRT indication and CRT present vs. absent was 68 vs. 65 years with 24% vs. 22% women in ESC-HF-LT, 76 vs. 74 years with 26% vs. 26% women in SwedeHF, and 70 years with 24% women in CRT Survey II (all had CRT). For ESC-HF-LT, independent predictors of having CRT were guideline-directed medical therapy (GDMT), atrial fibrillation (AF), prior HF hospitalization, and NYHA class. For SwedeHF, they were GDMT, age, AF, previous myocardial infarction, lower NYHA class, enrolment at university hospital, and follow-up at HF centre/Hospital. In SwedeHF, above median income and higher education level were also independently associated with having CRT. In the ESC-CRT Survey II (n = 11 088), all patients received CRT but with differences in the clinical characteristics between countries. CONCLUSION: CRT was used in a minority of eligible patients and more used in ESC-HF-LT than in SwedeHF.

Impact of the metal-to-artery ratio on clinical outcomes in left main and nonleft main bifurcation: insights the RAIN-CARDIOGROUP VII study (veRy thin stents for patients with left mAIn or bifurcatioN in real life).

INTRODUCTION: The impact on clinical outcomes of the metal coverage on the coronary surface (namely the metal-to-artery ratio) of currently used drug-eluting stents (DESs) has not been defined. METHODS: All patients with a left main or bifurcation stenosis treated with percutaneous coronary intervention (PCI) using ultrathin stents (struts thinner than 81 µm) were enrolled with a prospective multicentre fashion. The rate of device-oriented endpoint [DOE, defined as a composite of target lesion revascularization (TLR) and stent thrombosis] was the primary endpoint, while its single components were the secondary ones, evaluated according to the metal-to-artery ratio. RESULTS: After 14 ±â€Š10.4 months 62 (7.5%) of 830 patients undergoing PCI on left main experienced a DOE without differences in the metal-to-artery ratio (14.5 ±â€Š2.1 vs. 14.4 ±â€Š1.9, P = 0.51). Fifty out (2.4%) of 2082 patients treated with PCI on a coronary bifurcation other than left main experienced a DOE, with a higher mean metal-to-artery ratio (15.3 ±â€Š2.1 vs. 14.6 ±â€Š2, P = 0.01). At multivariate analysis, together with hypertension and diabetes, the metal-to-artery ratio was an independent predictor of DOE (hazard ratio 1.7 : 1.02-1.34, P = 0.02) in nonleft main PCI. When analysed for diameter, we found a significant correlation with DOE when the stent diameter was inferior to 3.0 mm (hazard ratio 1.21: 1.06-1.38, P < 0.01, all 95% confidence interval); this result was mainly consistent for patients treated with provisional stenting. The metal-to-artery ratio does not impact on outcomes in left main PCI, both in the provisional or two-stent technique, and generally when a drug-eluting stent more than 3.5 mm in diameter is implanted. Regarding nonleft main PCI, it is independently related to DOE and TLR, especially for DES with a diameter of 3.25 mm or less. CONCLUSION: The metal-to-artery ratio does not impact on outcomes in left main PCI, both in the provisional or two-stent technique, and generally when a drug-eluting stent more than 3.5 mm in diameter is implanted. Regarding nonleft main PCI, it is independently related to DOE and TLR, especially for DES with a diameter of 3.25 mm or less.

Impact of strut thickness and number of crown and connectors on clinical outcomes on patients treated with second-generation drug eluting stent.

INTRODUCTION: In new generation drug eluting stents (DESs) era, the impact of stent geometry on freedom from recurrent events has been poorly explored. Impact of struts thickness and the number of crowns and connectors on clinical outcomes were evaluated in the present study. METHODS: Randomized controlled trials comparing last generation DESs were selected. The primary endpoint was the rate of target lesion revascularization (TLR), while secondary was definite stent thrombosis (ST). RESULTS: Fifty-three studies with 52,006 patients were included. A struts thickness ≤81 nm was associated with a lower incidence of TLR (2.9%: 2.4-3.4 vs. 3.6%: 3.0-4.3) and ST (0.8%: 0.6-1.1 vs. 1.3%: 0.9-1.8). A mean number of connectors >2.5 was also associated with a lower incidence of TLR (3.2%: 2.8-3.6 vs. 3.5%: 2.9-4.2) and ST (1.0%:0.8-1.3 vs. 1.3%: 0.9-1.7 vs. for ST). On the other hand, stents with average number of crowns <7.5 did not perform better than stents with higher average number of crowns. CONCLUSIONS: The findings of the study support that lower struts thickness and higher numbers of connectors have a positive clinical outcome reducing stent thrombosis and target lesion revascularizations, while the average number of stent crowns plays a secondary role.

Diagnostic accuracy of functional, imaging and biochemical tests for patients presenting with chest pain to the emergency department: A systematic review and meta-analysis.

BACKGROUND: Non-invasive ischaemia tests and biomarkers are widely adopted to rule out acute coronary syndrome in the emergency department. Their diagnostic accuracy has yet to be precisely defined. METHODS: Medline, Cochrane Library CENTRAL, EMBASE and Biomed Central were systematically screened (start date 1 September 2016, end date 1 December 2016). Prospective studies (observational or randomised controlled trial) comparing functional/imaging or biochemical tests for patients presenting with chest pain to the emergency department were included. RESULTS: Overall, 77 studies were included, for a total of 49,541 patients (mean age 59.9 years). Fast and six-hour highly sensitive troponin T protocols did not show significant differences in their ability to detect acute coronary syndromes, as they reported a sensitivity and specificity of 0.89 (95% confidence interval 0.79-0.94) and 0.84 (0.74-0.9) vs 0.89 (0.78-0.94) and 0.83 (0.70-0.92), respectively. The addition of copeptin to troponin increased sensitivity and reduced specificity, without improving diagnostic accuracy. The diagnostic value of non-invasive tests for patients without troponin increase was tested. Coronary computed tomography showed the highest level of diagnostic accuracy (sensitivity 0.93 (0.81-0.98) and specificity 0.90 (0.93-0.94)), along with myocardial perfusion scintigraphy (sensitivity 0.85 (0.77-0.91) and specificity 0.92 (0.83-0.96)). Stress echography was inferior to coronary computed tomography but non-inferior to myocardial perfusion scintigraphy, while exercise testing showed the lower level of diagnostic accuracy. CONCLUSIONS: Fast and six-hour highly sensitive troponin T protocols provide an overall similar level of diagnostic accuracy to detect acute coronary syndrome. Among the non-invasive ischaemia tests for patients without troponin increase, coronary computed tomography and myocardial perfusion scintigraphy showed the highest sensitivity and specificity.

Is pericardial effusion a negative prognostic marker? Meta-analysis of outcomes of pericardial effusion.

BACKGROUND: The prognostic relevance and the prevalence of pericardial effusion in several diseases are not well established. The aim of this meta-analysis is to summarize the available evidence related to pericardial effusion prevalence and outcomes according to the cause. METHODS: Articles investigating the prognosis of pericardial effusion were identified by literature search. Twenty-three studies were finally included (17 022 patients). All-cause mortality was the primary end-point. Secondary end-point was the prevalence of pericardial effusion in most common diseases related to this clinical condition. RESULTS: The pooled prevalence of pericardial effusion was 19.5% [95% confidence interval (CI): 14.3-26]. After a mean follow-up of 36 ±â€Š23 months, the risk of death was higher in pericardial effusion patients [hazard ratio (HR) 1.59, 95% CI 1.37-1.85, P < 0.0001]. Stratifying for the main disease, pericardial effusion is associated with unfavourable outcome in all available subgroups: pulmonary arterial hypertension HR 1.53 (95% CI: 1.22-1.92; P < 0.0001), chronic heart failure (CHF) HR 1.53 (95% CI: 1.22-1.92; P < 0.0001), myocardial infarction HR 2.65 (95% CI: 1.4-4.99; P = 0.003) and malignancies HR 1.75 (95% CI: 1.09-2.81, P = 0.021). The lack of data concerning the idiopathic pericardial effusion does not permit a secure risk assessment but the average incidence of mortality is 14.5% (95% CI: 7.7-25.6). CONCLUSION: Pericardial effusion should be considered a marker of the severity of the underlying disease, whereas for idiopathic pericardial effusion the correlation with poor prognosis is less clear.

An innovative matrix controlling drug delivery produced by thermal treatment of DC tablets containing polycarbophil and ethylcellulose.

An innovative matrix, produced by thermal treatment on direct compression (DC) tablets containing polycarbophil (POL) and ethylcellulose (EC), identified as matrix forming polymers, and able to control the release of diltiazem hydrochloride, was developed. At pH 7.2, 72 ± 1.2% (w/w) of drug loaded was released in 25 h, mostly at constant rate. This swellable and unerodible matrix controls drug release by an anomalous transport mechanism. The modifications induced by the thermal treatment are irreversible and can be used to control and characterize the matrix. A 3-component constrained mixture design allowed the investigation of the experimental domain in which the matrix forms and the computation of a mathematical model that can be used to optimize the formulation properties. The release rate can be modulated (0.032-0.064% drug released/min) through the choice of suitable treatment conditions and tablet composition. The maximum amount of diltiazem hydrochloride released by zero-order kinetics, at the lowest release rate, occurs for POL:EC ratio in the range of 1:1-2:3 with 20-30% of diluent. The tablets are able to load up to 50% (w/w) of diltiazem hydrochloride without losing their properties. A stability study performed on a selected formulation containing DTZ showed stability for at least 2.7 years at RT conditions.

Study of retinoic acid polymorphism.

Some authors recently hypothesized the existence of a new retinoic acid (RA) phase in addition to the two already known polymorphs. We investigated RA polymorphism and our results exclude the presence of new modifications and refine the properties of the known forms. By comparison of simulated and acquired X-Ray Powder Diffraction (XRPD) it was possible to identify only the known monoclinic (I) and the triclinic (II) modifications; the same were also characterized by DSC, IR, and Raman spectroscopy. A solubility study associated to DSC allowed establishing an enantiotropic relationship between the two forms, with form II being less stable (DeltaGII/I=0.71 kJ/mol at 37 degrees C) below the transition temperature (136.6 degrees C; DeltaH=3.2 kJ/mol). The intrinsic dissolution rate (IDR) (I=61 microg/cm2xmin-1; II=125 microg/cm2xmin-1) confirmed this energetic relationship. The kinetics of solid transition I-->II was examined and its activation energy estimated (356 kJ/mol). The attempts to produce new phases allowed the development of methods to obtain the two polymorphs with high chemical and polymorphic purity. A validated DSC method is presented that enables detection of the presence of form I at a level of 1% (w/w) when in mixture with form II.