Evidence to support magnetic resonance conditional labelling of all pacemaker and defibrillator leads in patients with cardiac implantable electronic devices.

AIMS: Many cardiac pacemakers and defibrillators are not approved by regulators for magnetic resonance imaging (MRI). Even following generator exchange to an approved magnetic resonance (MR)-conditional model, many systems remain classified 'non-MR conditional' due to the leads. This classification makes patient access to MRI challenging, but there is no evidence of increased clinical risk. We compared the effect of MRI on non-MR conditional and MR-conditional pacemaker and defibrillator leads. METHODS AND RESULTS: Patients undergoing clinical 1.5T MRI with pacemakers and defibrillators in three centres over 5 years were included. Magnetic resonance imaging protocols were similar for MR-conditional and non-MR conditional systems. Devices were interrogated pre- and immediately post-scan, and at follow-up, and adverse clinical events recorded. Lead parameter changes peri-scan were stratified by MR-conditional labelling. A total of 1148 MRI examinations were performed in 970 patients (54% non-MR conditional systems, 39% defibrillators, 15% pacing-dependent) with 2268 leads. There were no lead-related adverse clinical events, and no clinically significant immediate or late lead parameter changes following MRI in either MR-conditional or non-MR conditional leads. Small reductions in atrial and right ventricular sensed amplitudes and impedances were similar between groups, with no difference in the proportion of leads with parameter changes greater than pre-defined thresholds (7.1%, 95% confidence interval: 6.1-8.3). CONCLUSIONS: There was no increased risk of MRI in patients with non-MR conditional pacemaker or defibrillator leads when following recommended protocols. Standardizing MR conditions for all leads would significantly improve access to MRI by enabling patients to be scanned in non-specialist centres, with no discernible incremental risk.

Multimodality Imaging for Cardiotoxicity: State of the Art and Future Perspectives.

ABSTRACT: Modern cancer therapies have significantly improved survival leading to a growing population of cancer survivors. Similarly, both conventional and newer treatments are associated with a spectrum of cardiovascular disorders with potential long-term sequelae. Prompt detection and treatment of these complications is, therefore, pivotal to enable healthy survivorship and reduce cardiovascular morbidity. Advanced multimodality imaging is a valuable tool for stratifying patient risk, identifying cardiovascular toxicity during and after therapy, and predicting recovery. This review summarizes the potential cardiotoxic complications of anticancer therapies and the multimodality approaches available in each case with special focus on newer techniques and the added value of biomarkers ultimately leading to earlier diagnosis and better prognostication.

Patterns of myocardial injury in recovered troponin-positive COVID-19 patients assessed by cardiovascular magnetic resonance.

BACKGROUND: Troponin elevation is common in hospitalized COVID-19 patients, but underlying aetiologies are ill-defined. We used multi-parametric cardiovascular magnetic resonance (CMR) to assess myocardial injury in recovered COVID-19 patients. METHODS AND RESULTS: One hundred and forty-eight patients (64 ± 12 years, 70% male) with severe COVID-19 infection [all requiring hospital admission, 48 (32%) requiring ventilatory support] and troponin elevation discharged from six hospitals underwent convalescent CMR (including adenosine stress perfusion if indicated) at median 68 days. Left ventricular (LV) function was normal in 89% (ejection fraction 67% ± 11%). Late gadolinium enhancement and/or ischaemia was found in 54% (80/148). This comprised myocarditis-like scar in 26% (39/148), infarction and/or ischaemia in 22% (32/148) and dual pathology in 6% (9/148). Myocarditis-like injury was limited to three or less myocardial segments in 88% (35/40) of cases with no associated LV dysfunction; of these, 30% had active myocarditis. Myocardial infarction was found in 19% (28/148) and inducible ischaemia in 26% (20/76) of those undergoing stress perfusion (including 7 with both infarction and ischaemia). Of patients with ischaemic injury pattern, 66% (27/41) had no past history of coronary disease. There was no evidence of diffuse fibrosis or oedema in the remote myocardium (T1: COVID-19 patients 1033 ± 41 ms vs. matched controls 1028 ± 35 ms; T2: COVID-19 46 ± 3 ms vs. matched controls 47 ± 3 ms). CONCLUSIONS: During convalescence after severe COVID-19 infection with troponin elevation, myocarditis-like injury can be encountered, with limited extent and minimal functional consequence. In a proportion of patients, there is evidence of possible ongoing localized inflammation. A quarter of patients had ischaemic heart disease, of which two-thirds had no previous history. Whether these observed findings represent pre-existing clinically silent disease or de novo COVID-19-related changes remain undetermined. Diffuse oedema or fibrosis was not detected.

Advanced Imaging Modalities to Monitor for Cardiotoxicity.

OPINION STATEMENT: Early detection and treatment of cardiotoxicity from cancer therapies is key to preventing a rise in adverse cardiovascular outcomes in cancer patients. Over-diagnosis of cardiotoxicity in this context is however equally hazardous, leading to patients receiving suboptimal cancer treatment, thereby impacting cancer outcomes. Accurate screening therefore depends on the widespread availability of sensitive and reproducible biomarkers of cardiotoxicity, which can clearly discriminate early disease. Blood biomarkers are limited in cardiovascular disease and clinicians generally still use generic screening with ejection fraction, based on historical local expertise and resources. Recently, however, there has been growing recognition that simple measurement of left ventricular ejection fraction using 2D echocardiography may not be optimal for screening: diagnostic accuracy, reproducibility and feasibility are limited. Modern cancer therapies affect many myocardial pathways: inflammatory, fibrotic, metabolic, vascular and myocyte function, meaning that multiple biomarkers may be needed to track myocardial cardiotoxicity. Advanced imaging modalities including cardiovascular magnetic resonance (CMR), computed tomography (CT) and positron emission tomography (PET) add improved sensitivity and insights into the underlying pathophysiology, as well as the ability to screen for other cardiotoxicities including coronary artery, valve and pericardial diseases resulting from cancer treatment. Delivering screening for cardiotoxicity using advanced imaging modalities will however require a significant change in current clinical pathways, with incorporation of machine learning algorithms into imaging analysis fundamental to improving efficiency and precision. In the future, we should aspire to personalized rather than generic screening, based on a patient's individual risk factors and the pathophysiological mechanisms of the cancer treatment they are receiving. We should aspire that progress in cardiooncology is able to track progress in oncology, and to ensure that the current 'one size fits all' approach to screening be obsolete in the very near future.

Resonance as the Mechanism of Daytime Periodic Breathing in Patients with Heart Failure.

RATIONALE: In patients with chronic heart failure, daytime oscillatory breathing at rest is associated with a high risk of mortality. Experimental evidence, including exaggerated ventilatory responses to CO2 and prolonged circulation time, implicates the ventilatory control system and suggests feedback instability (loop gain > 1) is responsible. However, daytime oscillatory patterns often appear remarkably irregular versus classic instability (Cheyne-Stokes respiration), suggesting our mechanistic understanding is limited. OBJECTIVES: We propose that daytime ventilatory oscillations generally result from a chemoreflex resonance, in which spontaneous biological variations in ventilatory drive repeatedly induce temporary and irregular ringing effects. Importantly, the ease with which spontaneous biological variations induce irregular oscillations (resonance "strength") rises profoundly as loop gain rises toward 1. We tested this hypothesis through a comparison of mathematical predictions against actual measurements in patients with heart failure and healthy control subjects. METHODS: In 25 patients with chronic heart failure and 25 control subjects, we examined spontaneous oscillations in ventilation and separately quantified loop gain using dynamic inspired CO2 stimulation. MEASUREMENTS AND MAIN RESULTS: Resonance was detected in 24 of 25 patients with heart failure and 18 of 25 control subjects. With increased loop gain-consequent to increased chemosensitivity and delay-the strength of spontaneous oscillations increased precipitously as predicted (r = 0.88), yielding larger (r = 0.78) and more regular (interpeak interval SD, r = -0.68) oscillations (P < 0.001 for all, both groups combined). CONCLUSIONS: Our study elucidates the mechanism underlying daytime ventilatory oscillations in heart failure and provides a means to measure and interpret these oscillations to reveal the underlying chemoreflex hypersensitivity and reduced stability that foretells mortality in this population.

Prognostic Value of Late Gadolinium Enhancement Cardiovascular Magnetic Resonance in Cardiac Amyloidosis.

BACKGROUND: The prognosis and treatment of the 2 main types of cardiac amyloidosis, immunoglobulin light chain (AL) and transthyretin (ATTR) amyloidosis, are substantially influenced by cardiac involvement. Cardiovascular magnetic resonance with late gadolinium enhancement (LGE) is a reference standard for the diagnosis of cardiac amyloidosis, but its potential for stratifying risk is unknown. METHODS AND RESULTS: Two hundred fifty prospectively recruited subjects, 122 patients with ATTR amyloid, 9 asymptomatic mutation carriers, and 119 patients with AL amyloidosis, underwent LGE cardiovascular magnetic resonance. Subjects were followed up for a mean of 24±13 months. LGE was performed with phase-sensitive inversion recovery (PSIR) and without (magnitude only). These were compared with extracellular volume measured with T1 mapping. PSIR was superior to magnitude-only inversion recovery LGE because PSIR always nulled the tissue (blood or myocardium) with the longest T1 (least gadolinium). LGE was classified into 3 patterns: none, subendocardial, and transmural, which were associated with increasing amyloid burden as defined by extracellular volume (P<0.0001), with transitions from none to subendocardial LGE at an extracellular volume of 0.40 to 0.43 (AL) and 0.39 to 0.40 (ATTR) and to transmural at 0.48 to 0.55 (AL) and 0.47 to 0.59 (ATTR). Sixty-seven patients (27%) died. Transmural LGE predicted death (hazard ratio, 5.4; 95% confidence interval, 2.1-13.7; P<0.0001) and remained independent after adjustment for N-terminal pro-brain natriuretic peptide, ejection fraction, stroke volume index, E/E', and left ventricular mass index (hazard ratio, 4.1; 95% confidence interval, 1.3-13.1; P<0.05). CONCLUSIONS: There is a continuum of cardiac involvement in systemic AL and ATTR amyloidosis. Transmural LGE is determined reliably by PSIR and represents advanced cardiac amyloidosis. The PSIR technique provides incremental information on outcome even after adjustment for known prognostic factors.

Patient-accessible tool for shared decision making in cardiovascular primary prevention: balancing longevity benefits against medication disutility.

BACKGROUND: Primary prevention guidelines focus on risk, often assuming negligible aversion to medication, yet most patients discontinue primary prevention statins within 3 years. We quantify real-world distribution of medication disutility and separately calculate the average utilities for a range of risk strata. METHOD AND RESULTS: We randomly sampled 360 members of the general public in London. Medication aversion was quantified as the gain in lifespan required by each individual to offset the inconvenience (disutility) of taking an idealized daily preventative tablet. In parallel, we constructed tables of expected gain in lifespan (utility) from initiating statin therapy for each age group, sex, and cardiovascular risk profile in the population. This allowed comparison of the widths of the distributions of medication disutility and of group-average expectation of longevity gain. Observed medication disutility ranged from 1 day to >10 years of life being required by subjects (median, 6 months; interquartile range, 1-36 months) to make daily preventative therapy worthwhile. Average expected longevity benefit from statins at ages ≥50 years ranges from 3.6 months (low-risk women) to 24.3 months (high-risk men). CONCLUSION: We can no longer assume that medication disutility is almost zero. Over one-quarter of subjects had disutility exceeding the group-average longevity gain from statins expected even for the highest-risk (ie, highest-gain) group. Future primary prevention studies might explore medication disutility in larger populations. Patients may differ more in disutility than in prospectively definable utility (which provides only group-average estimates). Consultations could be enriched by assessing disutility and exploring its reasons.

Evidence that conflict regarding size of haemodynamic response to interventricular delay optimization of cardiac resynchronization therapy may arise from differences in how atrioventricular delay is kept constant.

AIMS: Whether adjusting interventricular (VV) delay changes haemodynamic efficacy of cardiac resynchronization therapy (CRT) is controversial, with conflicting results. This study addresses whether the convention for keeping atrioventricular (AV) delay constant during VV optimization might explain these conflicts. METHOD AND RESULTS: Twenty-two patients in sinus rhythm with existing CRT underwent VV optimization using non-invasive systolic blood pressure. Interventricular optimization was performed with four methods for keeping the AV delay constant: (i) atrium and left ventricle delay kept constant, (ii) atrium and right ventricle delay kept constant, (iii) time to the first-activated ventricle kept constant, and (iv) time to the second-activated ventricle kept constant. In 11 patients this was performed with AV delay of 120 ms, and in 11 at AV optimum. At AV 120 ms, time to the first ventricular lead (left or right) was the overwhelming determinant of haemodynamics (13.75 mmHg at ±80 ms, P < 0.001) with no significant effect of time to second lead (0.47 mmHg, P = 0.50), P < 0.001 for difference. At AV optimum, time to first ventricular lead again had a larger effect (5.03 mmHg, P < 0.001) than time to second (2.92 mmHg, P = 0.001), P = 0.02 for difference. CONCLUSION: Time to first ventricular activation is the overwhelming determinant of circulatory function, regardless of whether this is the left or right ventricular lead. If this is kept constant, the effect of changing time to the second ventricle is small or nil, and is not beneficial. In practice, it may be advisable to leave VV delay at zero. Specifying how AV delay is kept fixed might make future VV delay research more enlightening.

Applicability of the iterative technique for cardiac resynchronization therapy optimization: full-disclosure, 50-sequential-patient dataset of transmitral Doppler traces, with implications for future research design and guidelines.

AIMS: Full-disclosure study describing Doppler patterns during iterative atrioventricular delay (AVD) optimization of biventricular pacemakers (cardiac resynchronization therapy, CRT). METHOD AND RESULTS: Doppler traces of the first 50 eligible patients undergoing iterative Doppler AVD optimization in the BRAVO trial were examined. Three experienced observers classified conformity to guideline-described patterns. Each observer then selected the optimum AVD on two separate occasions: blinded and unblinded to AVD. Four Doppler E-A patterns occurred: A (always merged, 18% of patients), B (incrementally less fusion at short AVDs, 12%), C (full separation at short AVDs, as described by the guidelines, 28%), and D (always separated, 42%). In Groups A and D (60%), the iterative guidelines therefore cannot specify one single AVD. On the kappa scale (0 = chance alone; 1 = perfect agreement), observer agreement for the ideal AVD in Classes B and C was poor (0.32) and appeared worse in Groups A and D (0.22). Blinding caused the scattering of the AVD selected as optimal to widen (standard deviation rising from 37 to 49 ms, P < 0.001). By blinding 28% of the selected optimum AVDs were ≤60 or ≥200 ms. All 50 Doppler datasets are presented, to support future methodological testing. CONCLUSION: In most patients, the iterative method does not clearly specify one AVD. In all the patients, agreement on the ideal AVD between skilled observers viewing identical images is poor. The iterative protocol may successfully exclude some extremely unsuitable AVDs, but so might simply accepting factory default. Irreproducibility of the gold standard also prevents alternative physiological optimization methods from being validated honestly.

Meta-analysis of the comparative effects of different classes of antihypertensive agents on brachial and central systolic blood pressure, and augmentation index.

AIMS: Brachial systolic blood pressure (bSBP) exceeds aortic pressure by a variable amount, and estimated central systolic blood pressure (cSBP) may be a better indicator of cardiovascular risk than bSBP. We undertook a systematic review and meta-analysis to compare the effect of single and multiple antihypertensive agents on bSBP, cSBP and augmentation index (AIx). METHODS: A random effects meta-analysis was performed on 24 randomized controlled trials of antihypertensives with measurements of bSBP, cSBP and/or AIx. Separate analyses were performed for drug comparisons with or without placebo, and drug combinations. RESULTS: In the placebo vs. drug meta-analysis, antihypertensive therapy reduced bSBP more than cSBP and there was no statistically significant evidence of heterogeneity by drug class, although the number of individual studies was small. In placebo-adjusted drug vs. drug comparison, treatment with ß-blockers, omapatrilat and thiazide diuretics lowered cSBP significantly less than bSBP (i.e. central to brachial amplification decreased), whereas other monotherapies lowered cSBP and bSBP to similar extents. Sample sizes were too small and effect estimates insufficiently precise to allow firm conclusions to be made regarding comparisons between individual drug classes. Antihypertensive combinations that included ß-blockers decreased central to brachial amplification. ß-Blockers increased AIx, whereas all other antihypertensive agents reduced AIx to similar extents. CONCLUSIONS: A reduction in central to brachial amplification by some classes of antihypertensive drug will result in lesser reductions in cSBP despite achievement of target bSBP. This effect could contribute to differences in outcomes in randomized clinical trials when ß-blocker- and/or diuretic-based antihypertensive therapy are compared with other regimens.

Burden and prognostic impact of cardiovascular disease in patients with cancer.

The number of patients at the intersection of cancer and cardiovascular disease (CVD) is increasing, reflecting ageing global populations, rising burden of shared cardiometabolic risk factors, and improved cancer survival. Many cancer treatments carry a risk of cardiotoxicity. Baseline cardiovascular risk assessment is recommended in all patients with cancer and requires consideration of individual patient risk and the cardiotoxicity profile of proposed anticancer therapies. Patients with pre-existing CVD are potentially at high or very high risk of cancer-therapy related cardiovascular toxicity. The detection of pre-existing CVD should prompt cardiac optimisation and planning of surveillance during cancer treatment. In patients with severe CVD, the risk of certain cancer therapies may be prohibitively high. Such decisions require multidisciplinary discussion with consideration of alternative anti-cancer therapies, risk-benefit assessment, and patient preference. Current practice is primarily guided by expert opinion and data from select clinical cohorts. There is need for development of a stronger evidence base to guide clinical practice in cardio-oncology. The establishment of multicentre international registries and national-level healthcare data linkage projects are important steps towards facilitating enrichment of cardio-oncology research programmes. In this narrative review, we consider epidemiological trends of cancer and CVD comorbidities and the impact of their co-occurrence on clinical outcomes, current approach to supporting cancer patients with pre-existing CVD and gaps in existing knowledge.

Characterizing the hypertensive cardiovascular phenotype in the UK Biobank.

AIMS: To describe hypertension-related cardiovascular magnetic resonance (CMR) phenotypes in the UK Biobank considering variations across patient populations. METHODS AND RESULTS: We studied 39 095 (51.5% women, mean age: 63.9 ± 7.7 years, 38.6% hypertensive) participants with CMR data available. Hypertension status was ascertained through health record linkage. Associations between hypertension and CMR metrics were estimated using multivariable linear regression adjusting for major vascular risk factors. Stratified analyses were performed by sex, ethnicity, time since hypertension diagnosis, and blood pressure (BP) control. Results are standardized beta coefficients, 95% confidence intervals, and P-values corrected for multiple testing. Hypertension was associated with concentric left ventricular (LV) hypertrophy (increased LV mass, wall thickness, concentricity index), poorer LV function (lower global function index, worse global longitudinal strain), larger left atrial (LA) volumes, lower LA ejection fraction, and lower aortic distensibility. Hypertension was linked to significantly lower myocardial native T1 and increased LV ejection fraction. Women had greater hypertension-related reduction in aortic compliance than men. The degree of hypertension-related LV hypertrophy was greatest in Black ethnicities. Increasing time since diagnosis of hypertension was linked to adverse remodelling. Hypertension-related remodelling was substantially attenuated in hypertensives with good BP control. CONCLUSION: Hypertension was associated with concentric LV hypertrophy, reduced LV function, dilated poorer functioning LA, and reduced aortic compliance. Whilst the overall pattern of remodelling was consistent across populations, women had greater hypertension-related reduction in aortic compliance and Black ethnicities showed the greatest LV mass increase. Importantly, adverse cardiovascular remodelling was markedly attenuated in hypertensives with good BP control.

Incident cardiovascular events and imaging phenotypes in UK Biobank participants with past cancer.

OBJECTIVES: To evaluate incident cardiovascular outcomes and imaging phenotypes in UK Biobank participants with previous cancer. METHODS: Cancer and cardiovascular disease (CVD) diagnoses were ascertained using health record linkage. Participants with cancer history (breast, lung, prostate, colorectal, uterus, haematological) were propensity matched on vascular risk factors to non-cancer controls. Competing risk regression was used to calculate subdistribution HRs (SHRs) for associations of cancer history with incident CVD (ischaemic heart disease (IHD), non-ischaemic cardiomyopathy (NICM), heart failure (HF), atrial fibrillation/flutter, stroke, pericarditis, venous thromboembolism (VTE)) and mortality outcomes (any CVD, IHD, HF/NICM, stroke, hypertensive disease) over 11.8±1.7 years of prospective follow-up. Linear regression was used to assess associations of cancer history with left ventricular (LV) and left atrial metrics. RESULTS: We studied 18 714 participants (67% women, age: 62 (IQR: 57-66) years, 97% white ethnicities) with cancer history, including 1354 individuals with cardiovascular magnetic resonance. Participants with cancer had high burden of vascular risk factors and prevalent CVDs. Haematological cancer was associated with increased risk of all incident CVDs considered (SHRs: 1.92-3.56), larger chamber volumes, lower ejection fractions, and poorer LV strain. Breast cancer was associated with increased risk of selected CVDs (NICM, HF, pericarditis and VTE; SHRs: 1.34-2.03), HF/NICM death, hypertensive disease death, lower LV ejection fraction, and lower LV global function index. Lung cancer was associated with increased risk of pericarditis, HF, and CVD death. Prostate cancer was linked to increased VTE risk. CONCLUSIONS: Cancer history is linked to increased risk of incident CVDs and adverse cardiac remodelling independent of shared vascular risk factors.

Maximizing efficiency of alternation algorithms for hemodynamic optimization of the AV delay of cardiac resynchronization therapy.

BACKGROUND: During optimization of the atrioventricular (AV) delay of cardiac resynchronization therapy (CRT), it is not known exactly which windows of time around the transition are most informative for identification of the optimum. METHOD AND RESULTS: IN 22 patients with CRT, we performed AV delay optimization using continuous noninvasive hemodynamics. We used signal-to-noise ratio to determine the most efficient averaging window location and width. We found that it is most efficient to position the averaging windows immediately before and immediately after the transition in AV delay. For example, skipping five beats after the transition decreases signal-to-noise ratio by 17.5% (P < 0.0001). Similarly, skipping five beats immediately before the transition reduces signal-to-noise ratio by 11.7% (P < 0.0001). The best choice of "fixed" averaging window width was found to be six beats, with signal-to-noise ratio falling by, for example, 41% for a one-beat window (P = 0.0002). However, even better was to set the window width for each patient to match one respiratory cycle. We observed that the pre- and posttransition signal-to-noise ratio traces begin to diverge three beats after the transition in AV delay. We believe this represents the time taken for the peripheral response to pacing-induced changes in stroke volume to occur. CONCLUSIONS: THE most efficient way to use alternating transitions for the hemodynamic optimization of CRT is to use an averaging window of one respiratory cycle, and not to skip any beats between the pretransition and posttransition averaging windows.

Role of cardiovascular magnetic resonance imaging in cardio-oncology.

Advances in cancer therapy have led to significantly longer cancer-free survival times over the last 40 years. Improved survivorship coupled with increasing recognition of an expanding range of adverse cardiovascular effects of many established and novel cancer therapies has highlighted the impact of cardiovascular disease in this population. This has led to the emergence of dedicated cardio-oncology services that can provide pre-treatment risk stratification, surveillance, diagnosis, and monitoring of cardiotoxicity during cancer therapies, and late effects screening following completion of treatment. Cardiovascular imaging and the development of imaging biomarkers that can accurately and reliably detect pre-clinical disease and enhance our understanding of the underlying pathophysiology of cancer treatment-related cardiotoxicity are becoming increasingly important. Multi-parametric cardiovascular magnetic resonance (CMR) is able to assess cardiac structure, function, and provide myocardial tissue characterization, and hence can be used to address a variety of important clinical questions in the emerging field of cardio-oncology. In this review, we discuss the current and potential future applications of CMR in the investigation and management of cancer patients.

Measurement of T1 Mapping in Patients With Cardiac Devices: Off-Resonance Error Extends Beyond Visual Artifact but Can Be Quantified and Corrected.

Background: Measurement of myocardial T1 is increasingly incorporated into standard cardiovascular magnetic resonance (CMR) protocols, however accuracy may be reduced in patients with metallic cardiovascular implants. Measurement is feasible in segments free from visual artifact, but there may still be off-resonance induced error. Aim: To quantify off-resonance induced T1 error in patients with metallic cardiovascular implants, and validate a method for error correction for a conventional MOLLI pulse sequence. Methods: Twenty-four patients with cardiac implantable electronic devices (CIEDs: 46% permanent pacemakers, PPMs; 33% implantable loop recorders, ILRs; and 21% implantable cardioverter-defibrillators, ICDs); and 31 patients with aortic valve replacement (AVR) (45% metallic) were studied. Paired mid-myocardial short-axis MOLLI and single breath-hold off-resonance field maps were acquired at 1.5 T. T1 values were measured by AHA segment, and segments with visual artifact were excluded. T1 correction was applied using a published relationship between off-resonance and T1. The accuracy of the correction was assessed in 10 healthy volunteers by measuring T1 before and after external placement of an ICD generator next to the chest to generate off-resonance. Results: T1 values in healthy volunteers with an ICD were underestimated compared to without (967 ± 52 vs. 997 ± 26 ms respectively, p = 0.0001), but were similar after correction (p = 0.57, residual difference 2 ± 27 ms). Artifact was visible in 4 ± 12, 42 ± 31, and 53 ± 27% of AHA segments in patients with ILRs, PPMs, and ICDs, respectively. In segments without artifact, T1 was underestimated by 63 ms (interquartile range: 7-143) per patient. The greatest error for patients with ILRs, PPMs and ICDs were 79, 146, and 191 ms, respectively. The presence of an AVR did not generate T1 error. Conclusion: Even when there is no visual artifact, there is error in T1 in patients with CIEDs, but not AVRs. Off-resonance field map acquisition can detect error in measured T1, and a correction can be applied to quantify T1 MOLLI accurately.

Age matters: differences in exercise-induced cardiovascular remodelling in young and middle aged healthy sedentary individuals.

AIMS: Remodelling of the cardiovascular system (including heart and vasculature) is a dynamic process influenced by multiple physiological and pathological factors. We sought to understand whether remodelling in response to a stimulus, exercise training, altered with healthy ageing. METHODS: A total of 237 untrained healthy male and female subjects volunteering for their first time marathon were recruited. At baseline and after 6 months of unsupervised training, race completers underwent tests including 1.5T cardiac magnetic resonance, brachial and non-invasive central blood pressure assessment. For analysis, runners were divided by age into under or over 35 years (U35, O35). RESULTS: Injury and completion rates were similar among the groups; 138 runners (U35: n = 71, women 49%; O35: n = 67, women 51%) completed the race. On average, U35 were faster by 37 minutes (12%). Training induced a small increase in left ventricular mass in both groups (3 g/m2, P < 0.001), but U35 also increased ventricular cavity sizes (left ventricular end-diastolic volume (EDV)i +3%; left ventricular end-systolic volume (ESV)i +8%; right ventricular end-diastolic volume (EDV)i +4%; right ventricular end-systolic volume (ESV)i +5%; P < 0.01 for all). Systemic aortic compliance fell in the whole sample by 7% (P = 0.020) and, especially in O35, also systemic vascular resistance (-4% in the whole sample, P = 0.04) and blood pressure (systolic/diastolic, whole sample: brachial -4/-3 mmHg, central -4/-2 mmHg, all P < 0.001; O35: brachial -6/-3 mmHg, central -6/-4 mmHg, all P < 0.001). CONCLUSION: Medium-term, unsupervised physical training in healthy sedentary individuals induces measurable remodelling of both heart and vasculature. This amount is age dependent, with predominant cardiac remodelling when younger and predominantly vascular remodelling when older.

Maximal Wall Thickness Measurement in Hypertrophic Cardiomyopathy: Biomarker Variability and its Impact on Clinical Care.

OBJECTIVES: The aim of this study was to define the variability of maximal wall thickness (MWT) measurements across modalities and predict its impact on care in patients with hypertrophic cardiomyopathy (HCM). BACKGROUND: Left ventricular MWT measured by echocardiography or cardiovascular magnetic resonance (CMR) contributes to the diagnosis of HCM, stratifies risk, and guides key decisions, including whether to place an implantable cardioverter-defibrillator (ICD). METHODS: A 20-center global network provided paired echocardiographic and CMR data sets from patients with HCM, from which 17 paired data sets of the highest quality were selected. These were presented as 7 randomly ordered pairs (at 6 cardiac conferences) to experienced readers who report HCM imaging in their daily practice, and their MWT caliper measurements were captured. The impact of measurement variability on ICD insertion decisions was estimated in 769 separately recruited multicenter patients with HCM using the European Society of Cardiology algorithm for 5-year risk for sudden cardiac death. RESULTS: MWT analysis was completed by 70 readers (from 6 continents; 91% with >5 years' experience). Seventy-nine percent and 68% scored echocardiographic and CMR image quality as excellent. For both modalities (echocardiographic and then CMR results), intramodality inter-reader MWT percentage variability was large (range -59% to 117% [SD ±20%] and -61% to 52% [SD ±11%], respectively). Agreement between modalities was low (SE of measurement 4.8 mm; 95% CI 4.3 mm-5.2 mm; r = 0.56 [modest correlation]). In the multicenter HCM cohort, this estimated echocardiographic MWT percentage variability (±20%) applied to the European Society of Cardiology algorithm reclassified risk in 19.5% of patients, which would have led to inappropriate ICD decision making in 1 in 7 patients with HCM (8.7% would have had ICD placement recommended despite potential low risk, and 6.8% would not have had ICD placement recommended despite intermediate or high risk). CONCLUSIONS: Using the best available images and experienced readers, MWT as a biomarker in HCM has a high degree of inter-reader variability and should be applied with caution as part of decision making for ICD insertion. Better standardization efforts in HCM recommendations by current governing societies are needed to improve clinical decision making in patients with HCM.