Progress in Cardiac Resynchronisation Therapy and Optimisation.

Cardiac resynchronisation therapy (CRT) has become the cornerstone of heart failure (HF) treatment. Despite the obvious benefit from this therapy, an estimated 30% of CRT patients do not respond ("non-responders"). The cause of "non-response" is multi-factorial and includes suboptimal device settings. To optimise CRT settings, echocardiography has been considered the gold standard but has limitations: it is user dependent and consumes time and resources. CRT proprietary algorithms have been developed to perform device optimisation efficiently and with limited resources. In this review, we discuss CRT optimisation including the various adopted proprietary algorithms and conduction system pacing.

Exercise Mode in Heart Failure: A Systematic Review and Meta-Analysis.

BACKGROUND: Optimising exercise prescription in heart failure (HF) with a preserved (HFpEF) or reduced (HFrEF) ejection fraction is clinically important. As such, the aim of this meta-analysis was to compare traditional moderate intensity training (MIT) against combined aerobic and resistance training (CT) and high-intensity interval training (HIIT) for improving aerobic capacity (VO2), as well as other clinically relevant parameters. METHODS: A comprehensive systematic search was performed to identify randomised controlled trials published between 1990 and May 2021. Research trials reporting the effects of MIT against CT or HIIT on peak VO2 in HFpEF or HFrEF were considered. Left-ventricular ejection fraction (LVEF) and various markers of diastolic function were also analysed. RESULTS: Seventeen studies were included in the final analysis, 4 of which compared MIT against CT and 13 compared MIT against HIIT. There were no significant differences between MIT and CT for peak VO2 (weighted mean difference [WMD]: 0.521 ml min-1 kg-1, [95% CI] = - 0.7 to 1.8, Pfixed = 0.412) or LVEF (WMD: - 1.129%, [95% CI] = - 3.8 to 1.5, Pfixed = 0.408). However, HIIT was significantly more effective than MIT at improving peak VO2 (WMD: 1.62 ml min-1 kg-1, [95% CI] = 0.6-2.6, Prandom = 0.002) and LVEF (WMD: 3.24%, [95% CI] = 1.7-4.8, Prandom < 0.001) in HF patients. When dichotomized by HF phenotype, HIIT remained significantly more effective than MIT in all analyses except for peak VO2 in HFpEF. CONCLUSIONS: HIIT is significantly more effective than MIT for improving peak VO2 and LVEF in HF patients. With the exception of peak VO2 in HFpEF, these findings remain consistent in both phenotypes. Separately, there is no difference in peak VO2 and LVEF change following MIT or CT, suggesting that the addition of resistance exercise does not inhibit aerobic adaptations in HF.

Successful Identification of and Discrimination Between Atrial and Ventricular Arrhythmia with the Aid of Pacing and Defibrillator Devices.

The presence of supraventricular tachycardia is the leading cause of inappropriate shock in ICD recipients, and it can be a significant cause of morbidity, psychological distress and worsened clinical outcome. Modern pacing and ICD systems offer a number of discriminators that are integrated into algorithms to differentiate sustained ventricular tachycardia from supraventricular tachycardia. These algorithms can be adapted and optimised for each individual patient to ensure that only those arrhythmias that need treatment through the use of an ICD, are actually treated. This review summarises the single- and dual-chamber discriminators that can be used in the detection and classification of tachyarrhythmias.

False-positive troponin elevation due to an immunoglobulin-G-cardiac troponin T complex: a case report.

BACKGROUND: Troponin is a crucial biomarker for the diagnosis of an acute coronary syndrome (ACS). It rises in response to myocardial injury from significant acute myocardial ischaemia caused by obstructive coronary artery disease ['classical' myocardial infarction (MI)]. However, raised levels have also been noted in conditions not recognized as classical ACS. This may include MI with non-obstructed coronary arteries such as takotsubo cardiomyopathy and other acute or chronic conditions such as pulmonary embolus or chronic kidney disease. This is commonly labelled as a 'falsely elevated' troponin although there is some myocardial strain to explain the rise, such as an increase in cardiac oxygen demand. True 'falsely elevated' troponin, characterized by a persistent elevation in the absence of cardiac injury does occur and thought to be secondary to an immunoglobulin-troponin complex (macrotroponin). CASE SUMMARY: A 53-year-old gentleman with a background of diabetes, hypertension, hypercholesterolaemia, and hepatitis B was admitted with chest pain and persistently elevated cardiac troponin T (cTnT) levels. Investigations revealed unobstructed coronary arteries and a structurally normal, well-functioning heart. Subsequent biochemical analysis found the persistently elevated cTnT secondary to macrotroponin T. DISCUSSION: Macrotroponin, an immunoglobulin-troponin bound complex should be considered as a differential diagnosis when the biochemistry is not reflective of the clinical picture. Early recognition requires effective collaboration with the biochemistry laboratory for accurate diagnosis.

Assessing the Eligibility Criteria in Phase III Randomized Controlled Trials of Drug Therapy in Heart Failure With Preserved Ejection Fraction: The Critical Play-Off Between a "Pure" Patient Phenotype and the Generalizability of Trial Findings.

AIMS: To investigate the effect of the different eligibility criteria used by phase III clinical studies in heart failure with preserved ejection fraction (HFpEF) on patient selection, phenotype, and survival. METHODS AND RESULTS: We applied the key eligibility criteria of 7 phase III HFpEF studies (Digitalis Investigation Group Ancillary, Candesartan in Patients With Chronic Heart Failure and Preserved Left-Ventricular Ejection Fraction, Perindopril in Elderly People With Chronic Heart Failure, Irbesartan in Heart Failure With Preserved Systolic Function, Japanese Diastolic Heart Failure, Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist, and Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction [PARAGON-HF; ongoing]) to a typical and well-characterized HFpEF population (n = 557) seen in modern European cardiological practice. Follow-up was available for a minimum of 24 months in each patient. Increasing the number of study eligibility criteria identifies a progressively smaller group of patients from real-life practice suitable for recruitment into clinical trials; using the J-DHF criteria, 81% of our clinic patients would have been eligible, whereas the PARAGON-HF criteria significantly reduced this proportion to 32%. The patients identified from our clinical population had similar mortality rates using the different criteria, which were consistently higher than those reported in the actual clinic trials. CONCLUSIONS: Trial eligibility criteria have become stricter with time, which reduces the number of eligible patients, affecting both generalizability of any findings and feasibility of completing an adequately powered trial. We could not find evidence that the additional criteria used in more recent randomized trials in HFpEF have identified patients at higher risk of all-cause mortality.

Cardiac computational modeling of ventricular tachycardia and cardiac resynchronization therapy: a clinical perspective.

Computational modeling has contributed to the understanding of the normal cardiac electrophysiology and the mechanisms underlying arrhythmogenesis and arrhythmia maintenance. Our improved understanding of cardiac physiology and access to faster computational power have allowed us to integrate many layers of biological systems, gain further insight into the mechanism of cardiac pathology and moved from small scale molecular and cellular models to integrated three-dimensional models representing the anatomy, electrophysiology and hemodynamic parameters on an organ scale. The ultimate goal of cardiac modeling is to create personalized patient-specific models that would allow clinicians to better understand the disease pathology, aid diagnosis and plan treatment strategy on a case-by-case basis. Pioneers in the field have demonstrated that such approach have already impacted on the diagnosis and therapeutic treatment for ventricular arrhythmia and heart failure. This review demonstrates the feasibility to integrate computational modeling with clinical investigations in a clinical environment and to guide therapeutic treatment of cardiac arrhythmia and heart failure in real time for individual patients.

Effect of atrioventricular optimization on circulating N-terminal pro brain natriuretic peptide following cardiac resynchronization therapy.

AIMS: Following CRT, atrioventricular (AV) optimization is not routinely practised. To evaluate its clinical utility, we examined the effect of AV delay optimization on the prognostic biomarker NT-proBNP. METHODS AND RESULTS: We prospectively studied 72 patients (mean age 73 ± 12.5 years, 70.8% male, 55.6% ischaemic) undergoing iterative AV optimization. Patients were divided into those whose nominal setting appeared ideal and not changed (Group 1, n = 22) and those whose AV delay was optimized (Group 2, n = 50). All patients underwent NT-proBNP assessment prior to CRT, and pre- and a median 5 days post-optimization. Compared with Group 1, NT-proBNP fell significantly in Group 2 patients (median 474 pg/mL) following optimization (P = 0.00001). A significant change in filling pattern (defined as a change in AV delay >50 ms) was required in 30% of patients, and it was this subgroup that derived the greater reduction in NT-proBNP levels [-1407 pg/mL, interquartile range (IQR) -3042 to -346 pg/mL] compared with those requiring <50 ms AV delay change (-125 pg/mL, IQR -1038 to 6 pg/mL), P = 0.0011. The benefit of AV optimization was principally observed in reverse remodelling non-responders (median -2167 pg/mL, IQR -3042 to -305 pg/mL) and in patients with a pseudonormal or restrictive filling pattern (median -1407 pg/mL, IQR -2809 to -342 pg/mL), compared with those with more benign diastolic filling (median - 264 pg/mL, IQR -1038 to -21 pg/mL), P = 0.033. CONCLUSIONS: In one-third of patients, major filling pattern changes are achieved with AV optimization, associated with subsequent rapid falls in NT-proBNP. The greater the AV delay change, the larger the NT-proBNP fall, and non-responders and those with restrictive or pseudonormal filling despite CRT are most likely to benefit.

Fragmented QRS complexes predict right ventricular dysfunction and outflow tract aneurysms in patients with repaired tetralogy of Fallot.

BACKGROUND: Fragmented QRS complexes (fQRS) correlate with myocardial scar, and may predict arrhythmias in patients with repaired tetralogy of Fallot (TOF). We investigated the relationship between fQRS in operated TOF patients with right ventricular (RV) dysfunction and RV outflow tract (RVOT) aneurysm. METHODS: We studied 56 operated TOF patients with moderate/severe pulmonary regurgitation, referred for cardiac magnetic resonance imaging (MRI) over a 4.5 year period. The presence of fQRS (additional notches in the R/S wave in ≥ 2 contiguous leads on the ECG) was correlated with MRI findings. RESULTS: fQRS was observed in 44 (78.6%) patients. Patients with fQRS had significantly larger RV end diastolic volume index (RVEDVi; 162 ml vs 141 ml, p=0.028) and RV end systolic volume index (RVESVi; 88 ml vs 70 ml, p=0.031). Increasing number of leads with fragmentation was independently associated with increasingly lower RV ejection fraction (adjusted co-efficient -0.97, 95%CI -1.83 to -0.12, p=0.026), greater pulmonary regurgitation fraction (1.65, 0.28 to 3.01, p=0.019), larger RVEDVi (6.78, 2.00 to 11.56, p=0.006) and RVESVi (5.41, 1.66 to 9.15, p=0.005). Anterior fragmentation correlated most significantly with RV dysfunction (p<0.05). fQRS had no significant association with LV dysfunction. Presence of any fQRS (OR 17.5, 95%CI 2.1-147.8, p=0.009) and inferior fQRS (OR 9.0, 95%CI 2.7-30.1, p<0.001) were found to be significant predictors for RVOT aneurysm. CONCLUSIONS: The presence of fQRS on the ECG is significantly associated with RV dysfunction and RVOT aneurysms in repaired TOF patients. Increasing burden of fragmentation, especially in the anterior leads, is associated with increasing RV dysfunction.

Rate-adaptive AV delay and exercise performance following cardiac resynchronization therapy.

BACKGROUND: Physiological shortening of the atrioventricular (AV) interval with increasing heart rate is well documented in normal human beings and is an established component of dual-chamber pacing for bradycardia. OBJECTIVES: To assess the effect of exercise on optimal AV delay and the impact of a patient-specific rate-adaptive AV delay (RAAVD) on exercise capacity in patients with heart failure following cardiac resynchronization therapy. METHODS: Phase 1: We performed iterative AV optimization at rest and exercise in 52 cardiac resynchronization therapy patients in atrial-sensed mode (mean age 71.6 ± 9.2 years, 25% females). Phase 2: Subsequently, 20 consecutive volunteers from this group (mean age 69.2 ± 9.6 years, 15% females) underwent cardiopulmonary exercise testing with RAAVD individually programmed ON (RAAVD-ON) or OFF (RAAVD-OFF). RESULTS: Phase 1: In 94% of the patients, there was a marked reduction (mean 50%) in optimal AV delay with exercise. The optimal resting vs exercise AV delay was 114.2 ± 29 ms at a heart rate of 64.4 ± 7.1 beats/min vs 57 ± 31 ms at a heart rate of 103 ± 13 beats/min (P < .001). No patients required an increase in AV delay with exercise, and 3 (6%) showed no change. Phase 2: With RAAVD-ON, significantly better exercise times were achieved (8.7 ± 3.2 minutes) compared with RAAVD-OFF (7.9 ± 3.2 minutes; P = .003), and there was a significant improvement in Vo(2)max (RAAVD-ON 16.1 ± 4.0 vs RAAVD-OFF 14.9 ± 3.7 mL/(kg · min); P = .024). CONCLUSIONS: There was a dramatic reduction in optimal AV delay with physiological exercise in the majority of this heart failure cardiac resynchronization therapy cohort. Replicating this physiological response with a programmable RAAVD translated into a 10% improvement in exercise capacity.

The implantable loop recorder-an important addition to the armentarium in the management of unexplained syncope.

INTRODUCTION: Unexplained syncope is a common condition with a significant impact both on the patient and on healthcare expenditure. Often, the diagnosis is hampered due to the temporary sporadic nature of the symptoms. Conventional monitoring methods have a low yield for identifying an abnormality during a spontaneous event. The implantable loop recorder (ILR), often underutilised, is an important diagnostic device that may fi ll this void in the early assessment of patients presenting with syncope. MATERIALS AND METHODS: This article begins with 2 case vignettes which highlight the clinical utility of ILRs in making a definitive diagnosis and guiding subsequent management. This is followed by a review of the existing evidence for ILRs, including the recent international guidelines, underpinning the role of ILRs in the present management algorithm of patients presenting with unexplained syncope. The technical aspects and cost implications will also be reviewed. RESULTS: Present evidence-based international guidelines have recommended the early use of ILRs in the management of patients with unexplained syncope. Furthermore, there may also be an important role for ILR use in patients with presumed epilepsy refractory to treatment and in the neurally mediated syncope cohort with recurrent symptoms. Cost benefit analysis also demonstrates advantages with early ILR use. CONCLUSION: The early use of ILR in selected patients remains an accurate, cost-effective, high yield tool for diagnosis and management of patients with unexplained syncope. However, its use should not detract from the importance of taking a detailed medical history and physical examination in the initial assessment to facilitate identification of the aetiology and risk stratification of patients.

Detection of atrial high-rate events by continuous home monitoring: clinical significance in the heart failure-cardiac resynchronization therapy population.

AIMS: Uncertainty exists over the importance of device-detected short-duration atrial arrhythmias. Continuous atrial diagnostics, through home monitoring (HM) technology (BIOTRONIK, Berlin, Germany), provides a unique opportunity to assess frequency and quantity of atrial fibrillation (AF) episodes defined as atrial high-rate events (AHRE). METHODS AND RESULTS: Prospective data from 560 heart failure (HF) patients (age 67 ± 10 years, median ejection fraction 27%) patients with a cardiac resynchronization therapy (CRT) device capable of HM from two multi-centre studies were analysed. Atrial high-rate events burden was defined as the duration of mode switch in a 24-h period with atrial rates of >180 beats for at least 1% or total of 14 min per day. The primary endpoint was incidence of a thromboembolic (TE) event. Secondary endpoints were cardiovascular death, hospitalization because of AF, or worsening HF. Over a median 370-day follow-up AHRE occurred in 40% of patients with 11 (2%) patients developing TE complications and mortality rate of 4.3% (24 deaths, 16 with cardiovascular aetiology). Compared with patients without detected AHRE, patients with detected AHRE>3.8 h over a day were nine times more likely to develop TE complications (P= 0.006). The majority of patients (73%) did not show a temporal association with the detected atrial episode and their adverse event, with a mean interval of 46.7 ± 71.9 days (range 0-194) before the TE complication. CONCLUSION: In a high-risk cohort of HF patients, device-detected atrial arrhythmias are associated with an increased incidence of TE events. A cut-off point of 3.8 h over 24 h was associated with significant increase in the event rate. Routine assessment of AHRE should be considered with other data when assessing stroke risk and considering anti-coagulation initiation and should also prompt the optimization of cardioprotective HF therapy in CRT patients.

Utility of high and standard right precordial leads during ajmaline testing for the diagnosis of Brugada syndrome.

AIMS: The authors sought to assess the value of the high right precordial leads (RPL) to detect the Type I Brugada ECG pattern in patients suspected of carrying Brugada syndrome (BrS). METHODS: Ajmaline testing using 15-lead ECGs was performed in 183 patients suspected of carrying BrS. Standard 12-lead ECG with V1-V3 recorded from the fourth intercostal space and an additional three leads placed over V1-V3 recorded from the third intercostal space were analysed. ECGs were analysed for a Type I ECG pattern in either the standard or high RPLs. RESULTS: Of the 183 tests, 31 (17%) were positive, and 152 were negative. In all positive studies, at least one high RPL became positive. In 13/31 (42%) cases, the Type I ECG pattern could be observed only in the high RPLs. Standard or high V3 were never positive before standard or high V1-V2. In seven patients, a Type I pattern was seen in one standard and one high RPL (vertical relationship). CONCLUSIONS: The high RPLs are more sensitive than the conventional 12-lead ECG alone and initial observations suggest that they remain specific for BrS, while standard and high lead V3 offer redundant data. A vertical relationship of type 1 patterns may have a similar diagnostic value to that of a horizontal pair.

Atherosclerotic plaque regression: fact or fiction?

Coronary artery disease is the major cause of death in the western world. The formation and rapid progression of atheromatous plaques can lead to serious cardiovascular events in patients with atherosclerosis. The better understanding, in recent years, of the mechanisms leading to atheromatous plaque growth and disruption and the availability of powerful HMG CoA-reductase inhibitors (statins) has permitted the consideration of plaque regression as a realistic therapeutic goal. This article reviews the existing evidence underpinning current therapeutic strategies aimed at achieving atherosclerotic plaque regression. In this review we also discuss imaging modalities for the assessment of plaque regression, predictors of regression and whether plaque regression is associated with a survival benefit.

Premature ventricular contractions arising from the pulmonary artery: the use of multielectrode array mapping and cryoablation.

Premature ventricular contractions with a left bundle branch block-like morphology and inferior axis typically originate from the right ventricular outflow tract; however, they can also originate from the pulmonary artery. We report two patients with frequent premature ventricular contractions who underwent successful cryoablation of ectopics arising from the posterolateral region of the pulmonary artery. The safe and effective use of cryoablation within the pulmonary artery is discussed. We recommend the use of noncontact mapping with multielectrode array catheter in facilitating the technique and providing a more accurate localization of the ectopic focus within the pulmonary artery, compared with conventional pace mapping methods.