Autosomal dominant cutis laxa and critical stenosis of the left main coronary artery in a 21-year-old female with an intronic mutation in the elastin gene.

Cutis laxa (CL) is a rare, inherited or acquired connective tissue disorder characterized by abnormal elastic fibers causing loose and redundant skin and a prematurely aged appearance. The syndrome has been associated with hypertension, but cases with early-onset ischemic heart disease have never been described. Here, we report a 21-year-old Danish female with activity-related shortness of breath and oedema of the lower extremities. The patient had a clinical diagnosis of autosomal dominant CL, but no genotyping had been performed prior to the index admission. The patient was diagnosed with ischemic heart disease, based on results of non-invasive cardiovascular imaging (including MRI and PET-CT) followed by invasive treatment of a critical left main coronary artery stenosis. Subsequent referral to genetic testing revealed a likely pathogenic intronic variant in ELN. This case report includes the clinical findings and relates these to known molecular mechanisms of CL.

The role of contractile dyssynchrony in pacing-induced cardiomyopathy: detailed assessment using index of contractile asymmetry.

AIMS: The pathophysiological effects of chronic right ventricular pacing and the role of right ventricular lead position are not well understood. Therefore, we investigated the association between left ventricular contractile dyssynchrony and pacing-induced cardiomyopathy (PICM) in patients with chronic right ventricular pacing. Furthermore, we assessed the association between right ventricular lead location and left ventricular contractile dyssynchrony. METHODS: This was a retrospective study using data from 153 pacemaker patients with normal (≥ 50%) pre-implant left ventricular ejection fraction (LVEF). Baseline and follow-up echocardiograms were analyzed, and PICM was defined as LVEF < 50% with ≥ 10% decrease in LVEF after pacemaker implantation. Relative index of contractile asymmetry (rICA), a novel strain rate-based method, was calculated to quantify left ventricular contractile dyssynchrony between opposing walls in the three apical views. Right ventricular lead position was categorized into anterior septum, posterior septum, free wall, and apex based on contrast-enhanced cardiac computed tomography. RESULTS: Forty-seven (31%) developed PICM. Overall contractile dyssynchrony, measured by mean rICA, was higher in the PICM group compared with the non-PICM group (1.19 ± 0.21 vs. 1.03 ± 0.19, p < 0.001). Left ventricular anterior-inferior dyssynchrony, assessed in the apical two-chamber view, was independently associated with PICM (p < 0.001). Thirty-seven (24%) leads were implanted anterior septal, 11 (7.2%) posterior septal, 74 (48.4%) apical, and 31 (20.3%) free wall. Left ventricular anterior-inferior dyssynchrony was significantly different between the four pacing lead locations (p < 0.01) with the highest rICA observed in the posterior septal group (1.30 ± 0.37). CONCLUSIONS: PICM is significantly associated increased contractile dyssynchrony assessed by rICA. This study suggests that especially left ventricular dyssynchrony in the anterior-inferior direction is associated with PICM, and pacing the right ventricular posterior septum resulted in the highest degree of anterior-inferior dyssynchrony. Quantification of left ventricular dyssynchrony by rICA provides important insights to the potential pathophysiology of PICM and the impact of right ventricular lead position.

Correction to: Prevalence and prognostic value of late gadolinium enhancement on CMR in aortic stenosis: meta-analysis.

The original version of this article, published on 12 August 2019, unfortunately contained a mistake. The funding note was incorrect; the correct funding note is given below.

Prevalence and prognostic value of late gadolinium enhancement on CMR in aortic stenosis: meta-analysis.

OBJECTIVES: The aim of this study was to investigate the prevalence and prognostic value of late gadolinium enhancement (LGE), as assessed by cardiovascular magnetic resonance (CMR) imaging, in patients with aortic stenosis. METHODS AND RESULTS: A systematic search of PubMed and EMBASE was performed, and observational cohort studies that analysed the prevalence of LGE and its relation to clinical outcomes in patients with aortic stenosis were included. Odds ratios were used to measure an effect of the presence of LGE on both all-cause and cardiovascular mortality. Nineteen studies were retrieved, accounting for 2032 patients (mean age 69.8 years, mean follow-up 2.8 years). We found that LGE is highly prevalent in aortic stenosis, affecting half of all patients (49.6%), with a non-infarct pattern being the most frequent type (63.6%). The estimated extent of focal fibrosis, expressed in % of LV mass, was equal to 3.83 (95% CI [2.14, 5.52], p < 0.0001). The meta-analysis showed that the presence of LGE was associated with increased all-cause (pooled OR [95% CI] = 3.26 [1.72, 6.18], p = 0.0003) and cardiovascular mortality (pooled OR [95% CI] = 2.89 [1.90, 4.38], p < 0.0001). CONCLUSIONS: LGE by CMR is highly prevalent in aortic stenosis patients and exhibits a substantial value in all-cause and cardiovascular mortality prediction. These results suggest a potential role of LGE in aortic stenosis patient risk stratification. KEY POINTS: • Up to the half of aortic stenosis patients are affected by myocardial focal fibrosis. • Sixty-four percent of focal fibrosis detected by LGE-CMR is non-infarct type. • The presence of focal fibrosis triples all-cause and cardiovascular mortality.

Prognostic value of myocardial fibrosis in severe aortic stenosis: study protocol for a prospective observational multi-center study (FIB-AS).

BACKGROUND: Adverse cardiac remodeling with a myocardial fibrosis as a key pathophysiologic component may be associated to worse survival in aortic stenosis (AS) patients. Therefore, with the application of advanced cardiac imaging we aim to investigate left ventricular myocardial fibrosis in severe AS patients undergoing aortic valve replacement (AVR) and determine its impact with post-intervention clinical outcomes. METHODS: In a prospective, observational, cohort study patients with severe AS scheduled either for surgical or transcatheter AVR will be recruited from two tertiary heart centers in Denmark and Lithuania. All patients will receive standard of care in accordance with the current guidelines and will undergo additional imaging testing before and after AVR: echocardiography with deformation analysis and cardiovascular magnetic resonance (CMR) with T1 parametric mapping. Those undergoing surgical AVR will also have a myocardial biopsy sampled at the time of a surgery for histological validation. Patients will be recruited over a 2-year period and followed up to 2 years to ascertain clinical outcomes. Follow-up CMR will be performed 12 months following AVR, and echocardiography with deformation analysis will be performed 3, 12, and 24 months following AVR. The study primary outcome is a composite of all-cause mortality and major adverse cardiovascular events. DISCUSSION: Despite continuous effort of research community there is still a lack of early predictors of left ventricular decompensation in AS, which could improve patient risk stratification and guide the optimal timing for aortic valve intervention, before irreversible left ventricular damage occurs. Advanced cardiac imaging and CMR derived markers of diffuse myocardial fibrosis could be utilized for this purpose. FIB-AS study is intended to invasively and non-invasively assess diffuse myocardial fibrosis in AS patients and investigate its prognostic significance in post-interventional outcomes. The results of the study will expand the current knowledge of cardiac remodeling in AS and will bring additional data on myocardial fibrosis and its clinical implications following AVR. ETHICS/DISSEMINATION: The study has full ethical approval and is actively recruiting patients. The results will be disseminated through scientific journals and conference presentations. TRIAL REGISTRATION: ClinicalTrials.govNCT03585933. Registered on 02 July 2018.

Index of contractile asymmetry improves patient selection for CRT: a proof-of-concept study.

BACKGROUND: Nearly one-third of heart failure (HF) patients do not respond to cardiac resynchronization therapy (CRT) despite having left bundle branch block (LBBB). The aim of the study was to investigate a novel method of quantifying left ventricular (LV) contractile asymmetry in HF. METHODS: Patients with HF and LBBB undergoing CRT (n = 89, 37.1% females, 68 ± 9 years, ischemic etiology in 61%, LV ejection fraction 27.1 ± 7.1%) were analyzed. LV longitudinal systolic strain rate values were extracted from curved anatomical M-mode plots of standard long-axis 2D-echocardiography images and cubic spline interpolation was used to generate a 3D-phantom. Index of contractile asymmetry (ICA) was calculated based on standard deviation of differences in strain rate of opposing walls. Average ICA was individually assessed pairwise in 12 opposing 30-degree LV sectors. Reduction in LV end-systolic volume (ESV) ≥15% after 6 months was considered as positive response to CRT. RESULTS: CRT response was found in 66 (74.2%) patients. Responders with both ischemic and non-ischemic cardiomyopathy had a higher and more extensive contractile asymmetry at baseline and achieved a greater ICA reduction after CRT than non-responders. Higher baseline ICA predicted higher degree and wider extent of ICA improvement. Also, both ICA at baseline and reduction of ICA correlated with the degree of ESV reduction after CRT. CONCLUSIONS: Quantification of asymmetrical LV activation in 3D by ICA provides valuable insights into LV contraction in case of LBBB and is a promising tool for improved patient selection for CRT.

Evaluation of ECG-gated [(11)C]acetate PET for measuring left ventricular volumes, mass, and myocardial external efficiency.

BACKGROUND: Noninvasive estimation of myocardial external efficiency (MEE) requires measurements of left ventricular (LV) oxygen consumption with [(11)C]acetate PET in addition to LV stroke volume and mass with cardiovascular magnetic resonance (CMR). Measuring LV geometry directly from ECG-gated [(11)C]acetate PET might enable MEE evaluation from a single PET scan. Therefore, we sought to establish the accuracy of measuring LV volumes, mass, and MEE directly from ECG-gated [(11)C]acetate PET. METHODS: Thirty-five subjects with aortic valve stenosis underwent ECG-gated [(11)C]acetate PET and CMR. List mode PET data were rebinned into 16-bin ECG-gated uptake images before measuring LV volumes and mass using commercial software and compared to CMR. Dynamic datasets were used for calculation of mean LV oxygen consumption and MEE. RESULTS: LV mass, volumes, and ejection fraction measured by CMR and PET correlated strongly (r = 0.86-0.92, P < .001 for all), but were underestimated by PET (P < .001 for all except ESV P = .79). PET-based MEE, corrected for bias, correlated fairly with PET/CMR-based MEE (r = 0.60, P < .001, bias -3 ± 21%, P = .56). PET-based MEE bias was strongly associated with LV wall thickness. CONCLUSIONS: Although analysis-related improvements in accuracy are recommended, LV geometry estimated from ECG-gated [(11)C]acetate PET correlate excellently with CMR and can indeed be used to evaluate MEE.

Radiotherapy in patients with pacemakers and implantable cardioverter defibrillators: a literature review.

An increasing number of patients with implantable cardiac rhythm devices undergo radiotherapy (RT) for cancer and are thereby exposed to the risk of device failure. Current safety recommendations seem to have limitations by not accounting for the risk of pacemakers and implantable cardioverter defibrillators malfunctioning at low radiation doses. Besides scant knowledge about optimal safety measures, only little is known about the exact prevalence of patients with devices undergoing RT. In this review, we provide a short overview of the principles of RT and present the current evidence on the predictors and mechanisms of device malfunctions during RT. We also summarize practical recommendations from recent publications and from the industry. Strongly associated with beam energy of photon RT, device malfunctions occur at ∼3% of RT courses, posing a substantial issue in clinical practice. Malfunctions described in the literature typically consist of transient software disturbances and only seldom manifest as a permanent damage of the device. Through close cooperation between cardiologists and oncologists, a tailored individualized approach might be necessary in this patient group in waiting time for updated international guidelines in the field.

Effects of intracoronary melatonin on ischemia-reperfusion injury in ST-elevation myocardial infarction.

Acute coronary occlusion is effectively treated by primary percutaneous coronary intervention. However, myocardial ischemia-reperfusion injury is at the moment an unavoidable consequence of the procedure. Oxidative stress is central in the development of ischemia-reperfusion injury. Melatonin, an endogenous hormone, acts through antioxidant mechanisms and could potentially minimize the myocardial injury. The aim of the experimental study was to examine the cardioprotective effects of melatonin in a porcine closed-chest reperfused infarction model. A total of 20 landrace pigs were randomized to a dosage of 200 mg (0.4 mg/mL) melatonin or placebo (saline). The intervention was administered intracoronary and intravenous. Infarct size, area at risk and microvascular obstruction were determined ex vivo by cardiovascular magnetic resonance imaging. Myocardial salvage index was calculated. The plasma levels of high-sensitive troponin T were assessed repeatedly. The experimenters were blinded with regard to treatment regimen. Melatonin did not significantly increase myocardial salvage index compared with placebo [melatonin 21.8% (16.1; 24.8) vs. placebo 20.2% (16.9; 27.0), p = 1.00]. The extent of microvascular obstruction was similar between the groups [melatonin 3.8% (2.7; 7.1) vs. placebo 3.7% (1.3; 7.7), p = 0.96]. The area under the curve for high-sensitive troponin T release was insignificantly reduced by 32% in the melatonin group [AUC melatonin 12,343.9 (6,889.2; 20,147.4) ng h/L vs. AUC placebo 18,285.3 (5,180.4; 23,716.8) ng h/L, p = 0.82]. Combined intracoronary and intravenous treatment with melatonin did not reduce myocardial reperfusion injury. The lack of a positive effect could be due to an ineffective dose of melatonin, a type II error or the timing of administration.

Risk of device malfunction in cancer patients with implantable cardiac device undergoing radiotherapy: a population-based cohort study.

BACKGROUND: Pacemakers (PMs) and implantable cardioverter defibrillators (ICDs) may develop malfunction during external beam radiotherapy (RT). We aimed to describe clinical practice in PM/ICD patients undergoing RT and to assess the rate and predictors of device malfunctions. METHODS: We reviewed medical records of all PM/ICD patients undergoing RT at four centers in Western Denmark during 2003-2012. Logistic regression was applied to identify predictors of PM/ICD malfunctions. RESULTS: Five hundred sixty patients were included. The annual rate of RT courses in PM/ICD patients increased by 199% from 1.45 treatments per 100,000 person-years in 2003 to 4.33 in 2012. Safety measures included supplementary evaluations of PM/ICD (38.3%), reprogramming (1.5%), relocation of the device (3.5%), and application of a magnet to the ICD during RT (10.8%). At device evaluations after the RT (n = 453), malfunctions were detected in 10 (2.5%) PMs and four (6.8%) ICDs. Electrical resets constituted 11 (78.6%) of the malfunctions, and no failures were life-threatening or warranted PM/ICD removal. Factors associated with device malfunctions in logistic regression analysis were beam energy ≥15 MV (odds ratio [OR] 5.73; 95% confidence interval [CI], 1.58-20.76) and location of tumor below the diaphragm (OR 4.31; 95% CI, 1.42-13.12). However, the effect of tumor location declined (OR 2.27; 95% CI, 0.65-7.95) after adjustment for beam energy. CONCLUSIONS: Although the rate of RT in PM/ICD patients is increasing, the damaging effects of RT on the devices seem to be usually transient. Our data suggest that high beam energy plays the pivotal role in inducing impairments in these devices.

The effect of radiotherapy beam energy on modern cardiac devices: an in vitro study.

AIMS: Radiotherapy (RT) for malignancies can harm pacemakers (PMs) and implantable cardioverter-defibrillators (ICDs). There is some evidence that, besides cumulative dose, the damaging radiation effects increase with beam energy. The aim of this study was to determine whether modern PMs and ICDs are more sensitive to high-energy than to low-energy photon beams. METHODS AND RESULTS: Two groups of unused PMs and explanted ICDs (five PMs and one ICD in each) were subjected to irradiations in a phantom with 6 and 18 megavolt (MV) photons, respectively. The devices were exposed to radiation at doses of 2 gray (Gy) daily to simulate two clinical scenarios with the PM/ICD in the RT field. A cumulative dose of 150 Gy was given to each device, corresponding to approximately twice the therapeutic dose. In the 6 MV group, one episode of PM malfunction was detected after reaching 150 Gy. In the 18 MV group, a total of 14 episodes of malfunction were detected starting at 30 Gy in all five PMs. No episodes appeared in the ICD, at the respective treatment groups. This corresponded to a hazard ratio of 9.11 [∼95% confidence interval (CI): 1.04-79.69] by Cox regression analysis between the two groups. In a repeated measures logistic regression model comparing the incidence rate of malfunctions, the odds ratio was 18.29 (∼95% CI: 1.52-219.41). CONCLUSION: Photon beam energy plays a considerable role in inducing implantable cardiac device malfunctions. Low-energy RT may be safer in PM/ICD patients despite relatively high radiation dose to the device.

Frequency of misdiagnosis in hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic Cardiomyopathy (HCM) is characterized by unexplained left ventricle hypertrophy (LVH) ≥15 mm. The condition is often hereditary and family screening is recommended to reduce the risk of adverse disease complications and premature death among relatives. Correct diagnosis of index patients is important to ensure that only relatives at risk of disease development are invited for family screening. PURPOSE: To investigate if patients with ICD-10 codes for HCM (DI421) or hypertrophic obstructive cardiomyopathy (DI422) fulfilled recognised diagnostic criteria. METHODS: All patients with ICD-10 codes for HCM or HOCM at a Department of Cardiology were identified and had their diagnosis validated by a cardiac investigation or a review of their medical records and previous investigations. RESULTS: Two hundred and forty patients had ICD-10 codes for HCM/HOCM, of whom 202 (84%, 202/240) underwent re-examination, while 38 (16%, 38/240) had their hospital notes reviewed. Seventy-six patients (32%, n = 76/240) did not fulfil diagnostic criteria, of whom 39, (51%, n = 39/76) had normal (10 mm) or modest LV wall thickness (11-14 mm). The remaining 37 patients (49%, n = 37/76) had LVH ≥15 mm, which was well-explained by uncontrolled hypertension, (32%, n = 24/76), aortic valve stenosis (19%, n = 7/76) or wild-type amyloidosis (16%, 6/76). CONCLUSION: One-third of patients with ICD-10 codes for HCM or HOCM did not fulfil recognised diagnostic criteria. Incorrect diagnosis of HCM may cause unnecessary family investigations which may be associated with anxiety, and a waste of health care resources. This highlights the need for specialised cardiomyopathy services to ensure correct diagnosis and management of HCM.

Effects of high-dose radiotherapy on implantable cardioverter defibrillators: an in vivo porcine study.

INTRODUCTION: Although the effects of radiotherapy (RT) on implantable cardioverter defibrillators (ICDs) have been studied in vitro, and some information has been gathered from case reports and series, no in vivo experiments have previously been performed. METHODS: In vivo effects of photon RT applied directly to five modern ICD generators from different manufacturers implanted in pigs were studied. The devices were interrogated between and after increasing doses of ionizing radiation. Afterwards, the shock function was tested. RESULTS: All ICDs withstood fractionated irradiations with a cumulative dose of 18.5 gray (Gy) of 6 megavolt (MV) photons and 18.5 Gy of 18 MV photons and were still fully functional. Especially, no oversense was recorded. Induced ventricular fibrillation was detected and treated properly by shock therapy in all cases. However, one of the ICDs converted to back-up mode later the same night. CONCLUSION: The animal model is feasible for investigating RT effects on implanted cardiac devices. During irradiations with 37 Gy, one recoverable malfunction was present in the tested devices. Additional animal studies could provide supplementary evidence for treating ICD patients, including recommendations for reprogramming of the ICD during RT and avoidance of relocating the device.

Novel non-invasive ECG imaging method based on the 12-lead ECG for reconstruction of ventricular activation: A proof-of-concept study.

Aim: Current non-invasive electrocardiographic imaging (ECGi) methods are often based on complex body surface potential mapping, limiting the clinical applicability. The aim of this pilot study was to evaluate the ability of a novel non-invasive ECGi method, based on the standard 12-lead ECG, to localize initial site of ventricular activation in right ventricular (RV) paced patients. Validation of the method was performed by comparing the ECGi reconstructed earliest site of activation against the true RV pacing site determined from cardiac computed tomography (CT). Methods: This was a retrospective study using data from 34 patients, previously implanted with a dual chamber pacemaker due to advanced atrioventricular block. True RV lead position was determined from analysis of a post-implant cardiac CT scan. The ECGi method was based on an inverse-ECG algorithm applying electrophysiological rules. The algorithm integrated information from an RV paced 12-lead ECG together with a CT-derived patient-specific heart-thorax geometric model to reconstruct a 3D electrical ventricular activation map. Results: The mean geodesic localization error (LE) between the ECGi reconstructed initial site of activation and the RV lead insertion site determined from CT was 13.9 ± 5.6 mm. The mean RV endocardial surface area was 146.0 ± 30.0 cm2 and the mean circular LE area was 7.0 ± 5.2 cm2 resulting in a relative LE of 5.0 ± 4.0%. Conclusion: We demonstrated a novel non-invasive ECGi method, based on the 12-lead ECG, that accurately localized the RV pacing site in relation to the ventricular anatomy.

Exploring myocardial fibrosis in severe aortic stenosis: echo, CMR and histology data from FIB-AS study.

Myocardial fibrosis in aortic stenosis is associated with worse survival following aortic valve replacement. We assessed myocardial fibrosis in severe AS patients, integrating echocardiographic, cardiovascular magnetic resonance (CMR) and histological data. A total of 83 severe AS patients (age 66.4 ± 8.3, 42% male) who were scheduled for surgical AVR underwent CMR with late gadolinium enhancement and T1 mapping and global longitudinal strain analysis. Collagen volume fraction was measured in myocardial biopsies (71) that were sampled at the time of AVR. Results. CVF correlated with imaging and serum biomarkers of LV systolic dysfunction and left side chamber enlargement and was higher in the sub-endocardium compared with midmyocardium (p<0.001). CVF median values were higher in LGE-positive versus LGE-negative patients [28.7% (19-33) vs 20.7% (15-30), respectively, p=0.040]. GLS was associated with invasively (CVF; r=-0.303, p=0.013) and non-invasively (native T1; r=-0.321, p<0.05) measured myocardial fibrosis. GLS and native T1 correlated with parameters of adverse LV remodelling, systolic and diastolic dysfunction and serum biomarkers of heart failure and myocardial injury. Conclusion. Our data highlight the role of myocardial fibrosis in adverse cardiac remodelling in AS. GLS has potential as a surrogate marker of myocardial fibrosis, and high native T1 and low GLS values differentiated patients with more advanced cardiac remodelling.

Familial hypercholesterolaemia: a study protocol for identification and investigation of potential causes and markers of subclinical coronary artery disease in the Faroe Islands.

INTRODUCTION: Familial hypercholesterolaemia (FH) is the most common monogenic autosomal dominant genetic disorder and is associated with a high risk of premature atherosclerotic cardiovascular disease. The prevalence of FH has been reported to be particularly high in certain founder populations. The population of the Faroe Islands is a founder population, but the prevalence of FH has never been investigated here. We aim to assess the prevalence of FH and to describe the genetic and clinical characteristics and potential causes of FH in the Faroe Islands. Furthermore, we aim to investigate whether indicators of subclinical coronary artery disease are associated with FH. METHODS AND ANALYSIS: The prevalence of FH will be estimated based on an electronic nationwide laboratory database that includes all measurements of plasma lipid levels in the Faroe Islands since 2006. Subsequently, we will identify and invite subjects aged between 18 and 75 years registered with a plasma low-density lipoprotein cholesterol above 6.7 mmol/L for diagnostic evaluation. Eligible FH cases will be matched to controls on age and sex. We aim to include 120 FH cases and 120 controls.Detailed information will be collected using questionnaires and interviews, and a physical examination will be undertaken. An adipose tissue biopsy and blood samples for genetic testing, detailed lipid analyses and samples for storage in a biobank for future research will be collected. Furthermore, FH cases and controls will be invited to have a transthoracic echocardiography and a cardiac CT performed. ETHICS AND DISSEMINATION: The project has been approved by the Ethical Committee and the Data Protection Agency of the Faroe Islands. The project is expected to provide important information, which will be published in international peer-reviewed journals.

Risk of Pacing-Induced Cardiomyopathy in Patients with High-Degree Atrioventricular Block-Impact of Right Ventricular Lead Position Confirmed by Computed Tomography.

Prospective studies applying fluoroscopy for assessment of right ventricular (RV) lead position have failed to show clear benefits from RV septal pacing. We investigated the impact of different RV lead positions verified by computed tomography (CT) on the risk of pacing-induced cardiomyopathy (PICM). We retrospectively included 153 patients who underwent routine fluoroscopy-guided pacemaker implantation between March 2012 and May 2020. All patients had normal pre-implant left ventricular ejection fraction (LVEF). Patients attended a follow-up visit including contrast-enhanced cardiac CT and transthoracic echocardiography. Patients were classified as septal or non-septal based on CT analysis. The primary endpoint was PICM (LVEF < 50% with ≥10% decrease after implantation). Based on CT, 48 (31.4%) leads were septal and 105 (68.6%) were non-septal. Over a median follow-up of 3.1 years, 16 patients (33.3%) in the septal group developed PICM compared to 31 (29.5%) in the non-septal group (p = 0.6). Overall, 13.1% deteriorated to LVEF ≤ 40%, 5.9% were upgraded to cardiac resynchronization therapy device, and 14.4% developed new-onset atrial fibrillation, with no significant differences between the groups. This study demonstrated a high risk of PICM despite normal pre-implant left ventricular systolic function with no significant difference between CT-verified RV septal or non-septal lead position.

Subclinical atherosclerosis determined by coronary artery calcium deposition in patients with clinical familial hypercholesterolemia.

Background and aims: Limited knowledge exists regarding the association between coronary artery calcium (CAC) deposition in patients with clinical familial hypercholesterolemia (FH) and FH subtypes such as polygenic causes. We studied CAC score in patients with clinical FH and subtypes including polygenic causes of FH compared to healthy controls. Methods: In a case-control study, we identified potential clinical FH cases registered with an LDL-C >6.7 mmol/l within a nationwide clinical laboratory database on the Faroe Islands and invited them for diagnostic evaluation according to clinical FH scoring systems. Controls were identified in the background population. All subjects were aged 18-75 years and without a history of cardiovascular disease. FH mutation testing and genotypes of twelve LDL-C associated single nucleotide polymorphisms were determined using conventional methods in selected individuals. CAC scores were assessed by cardiac CT. Odds ratios obtained using multivariate logistic regression were used as measures of association. Results: A total of 120 clinical FH patients and 117 age- and sex-matched controls were recruited. We found a very low frequency of monogenic FH (3%), but a high level of polygenic FH (60%) in those genetically tested (54%). There was a statistically significant association between the CAC score and a diagnosis of clinical FH with the highest observed odds ratio of 5.59 (95% CI 1.65; 18.94, p = 0.006) in those with a CAC score ≥300 compared to those with a CAC of zero. In supplemental analyses, there was a strong association between CAC scores and clinical FH of a polygenic cause. Conclusion: We found a statistically significant association between CAC levels and clinical FH with the highest observed risk estimates among clinical FH cases of a presumed polygenic cause.

The variability of 2D and 3D transthoracic echocardiography applied in a general population : Intermodality, inter- and intraobserver variability.

Assessment of the left ventricular (LV) function by three-dimensional echocardiography (3DE) is potentially superior to 2D echo echocardiography (2DE) for LV performance assessment. However, intra- and interobserver variation needs further investigation. We examined the intra- and interobserver variability between 2 and 3DE in a general population. In total, 150 participants from the Copenhagen City Heart Study were randomly chosen. Two observers assessed left ventricular ejection fraction (LVEF), end-diastolic (EDV) and end-systolic volumes (ESV) by 2DE and 3DE. Inter-, intraobserver and intermodality variabilities are presented as means of difference (MD), limits of agreement (LoA), coefficient of correlation (r), intraclass correlation coefficients (ICC). The lowest MD and LoA and highest r- and ICC-values was generally seen among the 3D acquisitions, with the 3D EDV interobserver as the best performing estimate (r = 0.95, ICC = 0.94). The largest MD, LoA and lowest r- and ICC-values was found in the interobserver 2D LVEF (r = 0.76, ICC = 0.63. For the intraobserver analysis, there were statistically significant differences between observations for all but 3DE EDV (p = 0.06). For interobserver analysis, there were statistically significant differences between observers for all estimates but 2DE EDV (p = 0.11), 3D ejection fraction (p = 0.9), 3DE EDV (p = 0.11) and 3D ESV (p = 0.15). Three-dimensional echocardiography is more robust and reproducible than 2DE and should be preferred for assessment of LV function.