Detailed analysis of electrogram peak frequency to guide ventricular tachycardia substrate mapping.

AIMS: Differentiating near-field (NF) and far-field (FF) electrograms (EGMs) is crucial in identifying critical arrhythmogenic substrate during ventricular tachycardia (VT) ablation. A novel algorithm annotates NF-fractionated signals enabling EGM peak frequency (PF) determination using wavelet transformation. This study evaluated the algorithms' effectiveness in identifying critical components of the VT circuit during substrate mapping. METHODS AND RESULTS: A multicentre, international cohort undergoing VT ablation was investigated. VT activation maps were used to demarcate the isthmus zone (IZ). Offline analysis was performed to evaluate the diagnostic performance of low-voltage area (LVA) PF substrate mapping. A total of 30 patients encompassing 198 935 EGMs were included. The IZ PF was significantly higher in sinus rhythm (SR) compared to right ventricular paced (RVp) substrate maps (234 Hz (195-294) vs. 197 Hz (166-220); P = 0.010). Compared to LVA PF, the IZ PF was significantly higher in both SR and RVp substrate maps (area under curve, AUC: 0.74 and 0.70, respectively). The LVA PF threshold of ≥200 Hz was optimal in SR maps (sensitivity 69%; specificity 64%) and RVp maps (sensitivity 60%; specificity 64%) in identifying the VT isthmus. In amiodarone-treated patients (n = 20), the SR substrate map IZ PF was significantly lower (222 Hz (186-257) vs. 303 Hz (244-375), P = 0.009) compared to amiodarone-naïve patients (n = 10). The ≥200 Hz LVA PF threshold resulted in an 80% freedom from VT with a trend towards reduced ablation lesions and radiofrequency times. CONCLUSION: LVA PF substrate mapping identifies critical components of the VT circuit with an optimal threshold of ≥200 Hz. Isthmus PF is influenced by chronic amiodarone therapy with lower values observed during RV pacing.

Beta-blockers and inhibitors of the renin-angiotensin aldosterone system for chronic heart failure with preserved ejection fraction.

BACKGROUND: Beta-blockers and inhibitors of the renin-angiotensin-aldosterone system improve survival and reduce morbidity in people with heart failure with reduced left ventricular ejection fraction (LVEF); a review of the evidence is required to determine whether these treatments are beneficial for people with heart failure with preserved ejection fraction (HFpEF). OBJECTIVES: To assess the effects of beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, angiotensin receptor neprilysin inhibitors, and mineralocorticoid receptor antagonists in people with HFpEF. SEARCH METHODS: We updated searches of CENTRAL, MEDLINE, Embase, and one clinical trial register on 14 May 2020 to identify eligible studies, with no language or date restrictions. We checked references from trial reports and review articles for additional studies.  SELECTION CRITERIA: We included randomised controlled trials with a parallel group design, enrolling adults with HFpEF, defined by LVEF greater than 40%. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included 41 randomised controlled trials (231 reports), totalling 23,492 participants across all comparisons. The risk of bias was frequently unclear and only five studies had a low risk of bias in all domains. Beta-blockers (BBs) We included 10 studies (3087 participants) investigating BBs. Five studies used a placebo comparator and in five the comparator was usual care. The mean age of participants ranged from 30 years to 81 years. A possible reduction in cardiovascular mortality was observed (risk ratio (RR) 0.78, 95% confidence interval (CI) 0.62 to 0.99; number needed to treat for an additional benefit (NNTB) 25; 1046 participants; three studies), however, the certainty of evidence was low. There may be little to no effect on all-cause mortality (RR 0.82, 95% CI 0.67 to 1.00; 1105 participants; four studies; low-certainty evidence). The effects on heart failure hospitalisation, hyperkalaemia, and quality of life remain uncertain. Mineralocorticoid receptor antagonists (MRAs) We included 13 studies (4459 participants) investigating MRA. Eight studies used a placebo comparator and in five the comparator was usual care. The mean age of participants ranged from 54.5 to 80 years. Pooled analysis indicated that MRA treatment probably reduces heart failure hospitalisation (RR 0.82, 95% CI 0.69 to 0.98; NNTB = 41; 3714 participants; three studies; moderate-certainty evidence). However, MRA treatment probably has little or no effect on all-cause mortality (RR 0.91, 95% CI 0.78 to 1.06; 4207 participants; five studies; moderate-certainty evidence) and cardiovascular mortality (RR 0.90, 95% CI 0.74 to 1.11; 4070 participants; three studies; moderate-certainty evidence). MRA treatment may have little or no effect on quality of life measures (mean difference (MD) 0.84, 95% CI -2.30 to 3.98; 511 participants; three studies; low-certainty evidence). MRA treatment was associated with a higher risk of hyperkalaemia (RR 2.11, 95% CI 1.77 to 2.51; number needed to treat for an additional harmful outcome (NNTH) = 11; 4291 participants; six studies; high-certainty evidence). Angiotensin-converting enzyme inhibitors (ACEIs) We included eight studies (2061 participants) investigating ACEIs. Three studies used a placebo comparator and in five the comparator was usual care. The mean age of participants ranged from 70 to 82 years. Pooled analyses with moderate-certainty evidence suggest that ACEI treatment likely has little or no effect on cardiovascular mortality (RR 0.93, 95% CI 0.61 to 1.42; 945 participants; two studies), all-cause mortality (RR 1.04, 95% CI 0.75 to 1.45; 1187 participants; five studies) and heart failure hospitalisation (RR 0.86, 95% CI 0.64 to 1.15; 1019 participants; three studies), and may result in little or no effect on the quality of life (MD -0.09, 95% CI -3.66 to 3.48; 154 participants; two studies; low-certainty evidence). The effects on hyperkalaemia remain uncertain. Angiotensin receptor blockers (ARBs) Eight studies (8755 participants) investigating ARBs were included. Five studies used a placebo comparator and in three the comparator was usual care. The mean age of participants ranged from 61 to 75 years. Pooled analyses with high certainty of evidence suggest that ARB treatment has little or no effect on cardiovascular mortality (RR 1.02, 95% 0.90 to 1.14; 7254 participants; three studies), all-cause mortality (RR 1.01, 95% CI 0.92 to 1.11; 7964 participants; four studies), heart failure hospitalisation (RR 0.92, 95% CI 0.83 to 1.02; 7254 participants; three studies), and quality of life (MD 0.41, 95% CI -0.86 to 1.67; 3117 participants; three studies). ARB was associated with a higher risk of hyperkalaemia (RR 1.88, 95% CI 1.07 to 3.33; 7148 participants; two studies; high-certainty evidence). Angiotensin receptor neprilysin inhibitors (ARNIs) Three studies (7702 participants) investigating ARNIs were included. Two studies used ARBs as the comparator and one used standardised medical therapy, based on participants' established treatments at enrolment. The mean age of participants ranged from 71 to 73 years. Results suggest that ARNIs may have little or no effect on cardiovascular mortality (RR 0.96, 95% CI 0.79 to 1.15; 4796 participants; one study; moderate-certainty evidence), all-cause mortality (RR 0.97, 95% CI 0.84 to 1.11; 7663 participants; three studies; high-certainty evidence), or quality of life (high-certainty evidence). However, ARNI treatment may result in a slight reduction in heart failure hospitalisation, compared to usual care (RR 0.89, 95% CI 0.80 to 1.00; 7362 participants; two studies; moderate-certainty evidence). ARNI treatment was associated with a reduced risk of hyperkalaemia compared with valsartan (RR 0.88, 95% CI 0.77 to 1.01; 5054 participants; two studies; moderate-certainty evidence). AUTHORS' CONCLUSIONS: There is evidence that MRA and ARNI treatment in HFpEF probably reduces heart failure hospitalisation but probably has little or no effect on cardiovascular mortality and quality of life. BB treatment may reduce the risk of cardiovascular mortality, however, further trials are needed. The current evidence for BBs, ACEIs, and ARBs is limited and does not support their use in HFpEF in the absence of an alternative indication. Although MRAs and ARNIs are probably effective at reducing the risk of heart failure hospitalisation, the treatment effect sizes are modest. There is a need for improved approaches to patient stratification to identify the subgroup of patients who are most likely to benefit from MRAs and ARNIs, as well as for an improved understanding of disease biology, and for new therapeutic approaches.

Beta-blockers and inhibitors of the renin-angiotensin aldosterone system for chronic heart failure with preserved ejection fraction.

BACKGROUND: Beta-blockers and inhibitors of the renin-angiotensin aldosterone system improve survival and reduce morbidity in people with heart failure with reduced left ventricular ejection fraction. There is uncertainty whether these treatments are beneficial for people with heart failure with preserved ejection fraction and a comprehensive review of the evidence is required. OBJECTIVES: To assess the effects of beta-blockers, angiotensin converting enzyme inhibitors, angiotensin receptor blockers, angiotensin receptor neprilysin inhibitors, and mineralocorticoid receptor antagonists in people with heart failure with preserved ejection fraction. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase and two clinical trial registries on 25 July 2017 to identify eligible studies. Reference lists from primary studies and review articles were checked for additional studies. There were no language or date restrictions. SELECTION CRITERIA: We included randomised controlled trials with a parallel group design enrolling adult participants with heart failure with preserved ejection fraction, defined by a left ventricular ejection fraction of greater than 40 percent. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies for inclusion and extracted data. The outcomes assessed included cardiovascular mortality, heart failure hospitalisation, hyperkalaemia, all-cause mortality and quality of life. Risk ratios (RR) and, where possible, hazard ratios (HR) were calculated for dichotomous outcomes. For continuous data, mean difference (MD) or standardised mean difference (SMD) were calculated. We contacted trialists where neccessary to obtain missing data. MAIN RESULTS: 37 randomised controlled trials (207 reports) were included across all comparisons with a total of 18,311 participants.Ten studies (3087 participants) investigating beta-blockers (BB) were included. A pooled analysis indicated a reduction in cardiovascular mortality (15% of participants in the intervention arm versus 19% in the control arm; RR 0.78; 95% confidence interval (CI) 0.62 to 0.99; number needed to treat to benefit (NNTB) 25; 1046 participants; 3 studies). However, the quality of evidence was low and no effect on cardiovascular mortality was observed when the analysis was limited to studies with a low risk of bias (RR 0.81; 95% CI 0.50 to 1.29; 643 participants; 1 study). There was no effect on all-cause mortality, heart failure hospitalisation or quality of life measures, however there is uncertainty about these effects given the limited evidence available.12 studies (4408 participants) investigating mineralocorticoid receptor antagonists (MRA) were included with the quality of evidence assessed as moderate. MRA treatment reduced heart failure hospitalisation (11% of participants in the intervention arm versus 14% in the control arm; RR 0.82; 95% CI 0.69 to 0.98; NNTB 41; 3714 participants; 3 studies; moderate-quality evidence) however, little or no effect on all-cause and cardiovascular mortality and quality of life measures was observed. MRA treatment was associated with a greater risk of hyperkalaemia (16% of participants in the intervention group versus 8% in the control group; RR 2.11; 95% CI 1.77 to 2.51; 4291 participants; 6 studies; high-quality evidence).Eight studies (2061 participants) investigating angiotensin converting enzyme inhibitors (ACEI) were included with the overall quality of evidence assessed as moderate. The evidence suggested that ACEI treatment likely has little or no effect on cardiovascular mortality, all-cause mortality, heart failure hospitalisation, or quality of life. Data for the effect of ACEI on hyperkalaemia were only available from one of the included studies.Eight studies (8755 participants) investigating angiotensin receptor blockers (ARB) were included with the overall quality of evidence assessed as high. The evidence suggested that treatment with ARB has little or no effect on cardiovascular mortality, all-cause mortality, heart failure hospitalisation, or quality of life. ARB was associated with an increased risk of hyperkalaemia (0.9% of participants in the intervention group versus 0.5% in the control group; RR 1.88; 95% CI 1.07 to 3.33; 7148 participants; 2 studies; high-quality evidence).We identified a single ongoing placebo-controlled study investigating the effect of angiotensin receptor neprilysin inhibitors (ARNI) in people with heart failure with preserved ejection fraction. AUTHORS' CONCLUSIONS: There is evidence that MRA treatment reduces heart failure hospitalisation in heart failure with preserverd ejection fraction, however the effects on mortality related outcomes and quality of life remain unclear. The available evidence for beta-blockers, ACEI, ARB and ARNI is limited and it remains uncertain whether these treatments have a role in the treatment of HFpEF in the absence of an alternative indication for their use. This comprehensive review highlights a persistent gap in the evidence that is currently being addressed through several large ongoing clinical trials.

Assessment of pericardial adhesions by means of the EpiCO2 technique: Brighton Adhesion Classification.

BACKGROUND: Epicardial ablation complications are more frequent in patients with preexisting pericardial adhesions. As opposed to the dry puncture technique, the coronary vein exit and carbon dioxide (CO2) insufflation (EpiCO2) technique allows diagnosing pericardial adhesions before subxiphoid puncture. OBJECTIVE: This study aimed to evaluate the efficacy of the EpiCO2 technique in diagnosing pericardial adhesions prior to subxiphoid puncture. METHODS: Following coronary vein exit, contrast was injected in the pericardial space, and adhesions classified using our novel Brighton Adhesion Classification (BAC) into BAC-0 (no adhesions), BAC-1 (dispersed adhesions), and BAC-2 (dense adhesions extending to the entire assessed area). CO2 insufflation allowed subclassification of BAC-1 adhesions into BAC-1a (not preventing epicardial access or restricting catheter movement) and BAC-1b (either preventing epicardial access or significantly limiting catheter movement). RESULTS: Intentional coronary vein exit (right atrial appendage exit in 1 case) was achieved in all 235 consecutive epicardial ablation procedures undertaken at our center. A diagnosis of BAC-0 was made in 219 cases (93.2%), BAC-1a in 9 cases (3.8%), BAC-1b in 2 cases (0.9%), and BAC-2 in 5 cases (2.1%). This led to not attempting subxiphoid puncture in 6 cases (2.6%) and abandoning epicardial mapping because of limited catheter movement in 1 case (0.4%). Access-related complications occurred in 7 cases (3%) only in the BAC-0 group. CONCLUSION: The EpiCO2 technique allows assessment of the presence of pericardial adhesions prior to attempting subxiphoid puncture for epicardial access, which may lead to a reduction in the procedural complications within this subset of patients.

The European Examination in Core Cardiology in Focus: Evaluation and Recommendations Using Educational Theory.

The European Examination in Core Cardiology (EECC) is a knowledge-based postgraduate examination for cardiology specialists in Europe. It is designed to assess if a trainee has gained sufficient knowledge for independent specialist practice in core cardiology. A critical evaluation of the ECCC was undertaken using current educational theory. Miller's Pyramid was considered, and the Utility Equation was employed in a mixed methods approach. The utility analysis findings were that the EECC measured well on reliability and validity although improvement could be made in educational impact, cost-effectiveness and accessibility. Recommendations for enhancement were then put forward. No assessment instrument is perfect, and it is important to remember that the EECC is one component of assessment strategy for specialist trainees, complementing other evidence of professional competence. After appraisal, while improvement can be made, the EECC fulfils its ambitions of assessment.

Radical freedom: Periyar and women.

This paper looks at South Indian social reformer and anti-caste radical Periyar E.V. Ramasamy's approach to the women's question. Periyar was not just an advocate of social and economic equality between the sexes but espoused a radical concept of sexual freedom for women, which is central to his concept of liberty as such. While the anti-colonialists of his period defended native traditions and customs, Periyar welcomed modernity and saw it laden with possibilities for the emancipation of women. Likewise, where other social reformers addressed the women's question within the ambit of the nation and/or the family, Periyar saw both nation and family as institutions that limited the liberties of women. This paper compares his thoughts with The Dialectic of Sex, the key work of the radical feminist Shulamith Firestone, and highlights the similarities in their approach to women's liberation and sexual freedom, especially their critique of child-rearing and child-bearing. It explores Periyar's booklet  Women Enslaved in detail and engages with lesser known, new primary material of Periyar on the women's question, concluding with a discussion of his perspective of the West.