The effect of trastuzumab on cardiac function in patients with HER2-positive metastatic breast cancer and reduced baseline left ventricular ejection fraction.

We investigated the effect of trastuzumab on cardiac function in a real-world historic cohort of patients with HER2-positive metastatic breast cancer (MBC) with reduced baseline left ventricular ejection fraction (LVEF). Thirty-seven patients with HER2-positive MBC and baseline LVEF of 40% to 49% were included. Median LVEF was 46% (interquartile range [IQR] 44%-48%) and median follow-up was 18 months (IQR 9-34 months). During this period, the LVEF did not worsen in 24/37 (65%) patients, while 13/37 (35%) patients developed severe cardiotoxicity defined as LVEF <40% with median time to severe cardiotoxicity of 7 months (IQR 4-10 months) after beginning trastuzumab. Severe cardiotoxicity was reversible (defined as LVEF increase to a value <5%-points below baseline value) in 7/13 (54%) patients, partly reversible (defined as absolute LVEF increase ≥10%-points from nadir to a value >5%-points below baseline) in 3/13 (23%) patients and irreversible (defined as absolute LVEF increase <10%-points from nadir and to a value >5%-points below baseline) in 3/13 (23%) patients. Likelihood of reversibility was numerically higher in patients who received cardio-protective medications (CPM), including ACE-inhibitors, beta-blockers and angiotensine-2 inhibitors, compared to those who did not receive any CPM (71% vs 13%, P = .091). Sixty-five percent of patients who received trastuzumab for HER2-positive MBC did not develop severe cardiotoxicity during a median follow-up of 18 months, despite having a compromised baseline LVEF. If severe cardiotoxicity occurred, it was at least partly reversible in more than two-thirds of the cases. Risks and benefits of trastuzumab use should be balanced carefully in this vulnerable population.

Upper Extremity Function following Transradial Percutaneous Coronary Intervention: Results of the ARCUS Trial.

Objectives: To determine the incidence of upper extremity dysfunction (UED), after a transradial percutaneous coronary intervention (TR-PCI). Background: Transradial approach (TRA) is the preferred approach for coronary interventions. However, upper extremity complications may be underreported. Methods: The ARCUS was designed as a prospective cohort study, including 502 consecutive patients admitted for PCI. Patients treated with transfemoral PCI (TF-PCI) acted as a control group. A composite score of physical examinations and questionnaires was used for determining UED. Clinical outcomes were monitored during six months of follow-up, with its primary endpoint at two weeks. Results: A total of 440 TR-PCI and 62 control patients were included. Complete case analysis (n = 330) at 2 weeks of follow-up showed that UED in the TR-PCI group was significantly higher than that in the TF-PCI group: 32.7% versus 13.9%, respectively (p=0.04). The three impaired variables most contributing to UED were impaired elbow extension, wrist flexion, and extension. Multivariate logistic regression showed that smokers were almost three times more likely to develop UED. Conclusions: This study demonstrates that UED seems to occur two times more in TR-PCI than in TF-PCI at 2 weeks of follow-up. However, no significant long-term difference or difference between the intervention arm and the contralateral arm was found at all timepoints.

2D-echocardiography vs cardiac MRI strain: a prospective cohort study in patients with HER2-positive breast cancer undergoing trastuzumab.

BACKGROUND: We aimed to study the predictive value of early two-dimensional echocardiography (2DE) speckle tracking (ST) for left ventricular ejection fraction (LVEF) changes during trastuzumab treatment for HER2-positive breast cancer. METHODS: HER2-positive breast cancer patients receiving trastuzumab, with or without anthracycline, underwent 2DE-ST at baseline and after 3 and 6 months (m) trastuzumab. Cardiac magnetic resonance (CMR) imaging (with ST) was performed at baseline and 6 m. We studied the correlation between 2DE-ST- and CMR-derived global longitudinal strain (GLS) and global radial strain (GRS) measured at the same time. Additionally, we associated baseline and 3 m 2DE-ST measurements with later CMR-LVEF, and with cardiotoxicity, defined as CMR-LVEF < 45% and/or absolute decline > 10% during trastuzumab. RESULTS: Forty-seven patients were included. Median baseline LVEF was 60.4%. GLS measurements based on 2DE-ST and CMR showed weak correlation (Pearson's r = 0.33; p = 0.041); GRS measurements were uncorrelated (r = 0.09; p = 0.979). 2DE-LVEF at baseline and 3 m, and 2DE-ST-GLS at 3 m were predictive of CMR-LVEF at 6 m. In contrast, the change in 2DE-ST-GLS at 3 m was predictive of the change in CMR-LVEF at 6 m, whereas the change in 2DE-LVEF was not. Importantly, the 11 patients who developed cardiotoxicity (28%) had larger 2DE-ST-GLS change at 3 m than those who did not (median 5.2%-points versus 1.7%-points; odds ratio for 1% difference change 1.81, 95% confidence interval 1.11-2.93; p = 0.016; explained variance 0.34). CONCLUSIONS: Correlations between 2DE-ST and CMR-derived measurements are weak. Nevertheless, ST-measurements appeared useful to improve the performance of 2DE in predicting LVEF changes after 6 m of trastuzumab treatment.

Impact of machine-learning CT-derived fractional flow reserve for the diagnosis and management of coronary artery disease in the randomized CRESCENT trials.

OBJECTIVE: To determine the potential impact of on-site CT-derived fractional flow reserve (CT-FFR) on the diagnostic efficiency and effectiveness of coronary CT angiography (CCTA) in patients with obstructive coronary artery disease (CAD) on CCTA. METHODS: This observational cohort study included patients with suspected CAD who had been randomized to cardiac CT in the CRESCENT I and II trials. On-site CT-FFR was blindly performed in all patients with at least one ≥ 50% stenosis on CCTA and no exclusion criteria for CT-FFR. We retrospectively assessed the effect of adding CT-FFR to the CT protocol in patients with a stenosis ≥ 50% on CCTA in terms of diagnostic effectiveness, i.e., the number of additional tests required to determine the final diagnosis, reclassification of the initial management strategy, and invasive coronary angiography (ICA) efficiency, i.e., ICA rate without ≥ 50% CAD. RESULTS: Fifty-three patients out of the 372 patients (14%) had at least one ≥ 50% stenosis on CCTA of whom 42/53 patients (79%) had no exclusion criteria for CT-FFR. CT-FFR showed a hemodynamically significant stenosis (≤ 0.80) in 27/53 patients (51%). The availability of CT-FFR would have reduced the number of patients requiring additional testing by 57%-points compared with CCTA alone (37/53 vs. 7/53, p < 0.001). The initial management strategy would have changed for 30 patients (57%, p < 0.001). Reserving ICA for patients with a CT-FFR ≤ 0.80 would have reduced the number of ICA following CCTA by 13%-points (p = 0.016). CONCLUSION: Implementation of on-site CT-FFR may change management and improve diagnostic efficiency and effectiveness in patients with obstructive CAD on CCTA. KEY POINTS: • The availability of on-site CT-FFR in the diagnostic evaluation of patients with obstructive CAD on CCTA would have significantly reduced the number of patients requiring additional testing compared with CCTA alone. • The implementation of on-site CT-FFR would have changed the initial management strategy significantly in the patients with obstructive CAD on CCTA. • Restricting ICA to patients with a positive CT-FFR would have significantly reduced the ICA rate in patients with obstructive CAD on CCTA.

Rationale and design of the ARCUS: Effects of trAnsRadial perCUtaneouS coronary intervention on upper extremity function.

OBJECTIVE: The aim of this study is to provide a complete insight in the access-site morbidity and upper extremity function after Transradial Percutaneous Coronary Intervention (TR-PCI). BACKGROUND: In percutaneous coronary intervention the Transradial Approach (TRA) is gaining popularity as a default technique. It is a very promising technique with respect to post-procedure complications, but the exact effects of TRA on upper extremity function are unknown. METHODS AND RESULTS: The effects of trAnsRadial perCUtaneouS coronary intervention on upper extremity function (ARCUS) trial is a multicenter prospective cohort study that will be conducted in all patients admitted for TR-PCI. Clinical outcomes will be monitored during a follow-up of 6 months, with its primary endpoint at two weeks of follow-up. To investigate the complete upper extremity function, a combination of physical examinations and validated questionnaires will be used to provide information on anatomical integrity, strength, range of motion (ROM), coordination, sensibility, pain, and functioning in everyday life. Procedural and material specifications will be registered in order to include all possible aspects influencing upper extremity function. CONCLUSIONS: Results from this study will elucidate the effect of TR-PCI on upper extremity function. This creates the opportunity to further optimize TR-PCI, to make improvements in functional outcome and to prevent morbidity regarding full upper extremity function. © 2016 Wiley Periodicals, Inc.

Mitochondrial Cardiomyopathy: Distinctive Cardiac Phenotype Detected with Cardiovascular MRI.

Left ventricular hypertrophy (LVH) has a broad differential diagnosis. Pathogenic variants of mitochondrial DNA are a rare cause of LVH, and cardiac MRI is a powerful technique that may aid in differentiating such rare causes. This case report presents three siblings with a pathogenic variant of the mitochondrially encoded tRNA isoleucine (MT-TI) gene. A distinctive cardiac phenotype was detected with cardiac MRI. Extensive LVH and dilatation and decreased ejection fraction were observed with a pattern of increased T2 signal and extensive late gadolinium enhancement, which was remarkably consistent among all three siblings. Keywords: Cardiomyopathies, MR Imaging, Hypertrophic Cardiomyopathy, Mitochondrial, Inherited Cardiomyopathy, Left Ventricular Hypertrophy, Cardiovascular MRI, Late Gadolinium Enhancement Supplemental material is available for this article. © RSNA, 2023.

Minor elevations in troponin I are associated with mortality and adverse cardiac events in patients with atrial fibrillation.

AIMS: In patients with atrial fibrillation, minor troponin I elevation is regularly detected; however, the prognostic significance of this finding is unknown. We therefore sought to examine the prognostic value of elevated troponin I in patients with atrial fibrillation. METHODS AND RESULTS: A prospective study was conducted analysing all consecutive patients admitted with atrial fibrillation in a 2-year period. Patients with an ST-elevation myocardial infarction (MI) were excluded. Minor troponin elevation was defined as a troponin I level between 0.15 and 0.65 ng/mL, which is still below the 99th percentile of the upper reference limit. A positive troponin I was defined as ≥ 0.65 ng/mL. Study outcomes were all-cause mortality (death), death and myocardial infarction (death/MI), or all major adverse cardiac events (MACE: death, MI, or revascularization). A total of 407 patients were eligible for inclusion. The median duration of follow-up was 688 days. A minor elevation occurred in 81 (20%) patients and 77 (19%) had a positive troponin I. In a multivariate model, minor troponin I elevation and a positive troponin I were independently associated with death [hazard ratio (HR): 2.36, 95% confidence interval (CI): 1.17-4.73 for minor elevation and HR: 3.77, 95% CI: 1.42-10.02 for positive troponin I]. Also, there was an independent correlation between the combined endpoints of death/MI and MACE and both a minor elevation and a positive troponin I. CONCLUSION: Minor elevations in troponin I on hospital admission are associated with mortality and cardiac events in patients with atrial fibrillation and might be useful for risk stratification.

Treatment and Management of Upper Extremity Dysfunction Following Transradial Percutaneous Coronary Intervention: A Prospective Cohort Study.

BACKGROUND: The transradial artery access is the benchmark approach in transradial percutaneous coronary intervention (TR-PCI). The purpose of this study was to evaluate the different complications, treatments, and outcome of upper extremity dysfunction following a TR-PCI. METHODS: This was a prospective cohort substudy of patients with access-site complications. The study population consisted of 433 patients treated with TR-PCI. Referral to the hand center was mandated if the patient experienced new-onset or increase of preexistent symptoms in the upper extremity. Patients were followed up to the last control visit (5-7 months after the index procedure) at the hand center. Outcome results were categorized in "symptom-free," "improvement of symptoms," and "no improvement." RESULTS: Forty-one (9% of total) patients underwent assessment at the hand center. Most frequent referral indication was pain in the intervention arm. Women, preexisting sensibility disorder, and osteoarthritis in the intervention arm were associated with increased odds of referral. The most common complications diagnosed were carpal tunnel syndrome (n = 18) and osteoarthritis (n = 15). Thirty patients required further medical treatment. Immobilization therapy was most applied. Seventeen (4% of total) patients had persisting symptoms despite medical treatment. CONCLUSIONS: The occurrence of complications in the upper extremity after a TR-PCI is small. Despite medical treatment, symptoms persisted in 4% of all patients treated with TR-PCI. Possible explanations for the persisting symptoms are exacerbation of latent osteoarthritis and carpal tunnel syndrome by trauma-induced edema. Awareness of TR-PCI-induced complications among all specialists is essential to optimize patient care.

The predictive value of cardiac biomarkers in prognosis and risk stratification of patients with atrial fibrillation.

PURPOSE OF REVIEW: Atrial fibrillation is a significant public health issue considering its high prevalence in the general population, and is associated with an increased risk of cardiovascular mortality and morbidity and thrombo-embolic complications.Asymptomatic paroxysms of atrial fibrillation occur frequently in the first stages of the disease but patients present to the doctor at a relatively late stage when the associated complications have already taken place. It is crucial to identify such patients as early as possible in order to start preventive therapy. Clinical diagnostic tests to identify patients prone to atrial fibrillation complications have not yet been developed as the exact mechanism and substrate of subclinical atrial fibrillation are not known. Further research is necessary to understand the pathophysiology of subclinical atrial fibrillation and to identify potential risk markers that determine the development and prognosis of the disease. RECENT FINDINGS: Biomarkers have recently been identified which have been shown to be related to the incidence of atrial fibrillation and its prognosis. They reflect inflammation, neurohumoral activation and subclinical heart damage. SUMMARY: New biomarkers may help to understand the mechanisms of subclinical atrial fibrillation and signal the likelihood of disease progression. Such biomarkers, though subject to further validation, may be of value in predicting the prognosis and guiding the treatment of patients with atrial fibrillation. They may enhance the ability of risk scores to guide anticoagulant treatment strategies.

Brachial Artery Thrombosis as a Presentation of Non-Small Cell Pulmonary Carcinoma Growing Into the Left Atrium.

We present a case of a thrombus in the left brachial artery as a cardioembolic presentation of pulmonary carcinoma. There have been few reports describing this clinical presentation, but if present, prognosis is very poor. Therefore, a cardioembolic event should be borne in mind as an atypical presentation of pulmonary carcinoma. (Level of Difficulty: Beginner.).

Usefulness of High-Sensitivity Cardiac Troponin T to Predict Long-Term Outcome in Patients with Hypertrophic Cardiomyopathy.

Since the first report of an association between cardiac troponin (cTn) and adverse outcome in hypertrophic cardiomyopathy (HD), there is a paucity in confirmative data. We performed a prospective, prespecified 5-year follow-up cohort study of 135 HC patients who participated in a national multicenter project and underwent clinical evaluation, MRI (cine, LGE and T2-weighted imaging) and biomarker assessment (high-sensitivity cTnT (hs-cTnT), N-terminal pro-B-type natriuretic peptide, soluble tumorgenicity suppressor-2, Galectin-3, Growth differentiation factor-15, C-terminal Propeptide of Type I Collagen (CICP)). An elevated hs-cTnT concentration was defined as ≥14ng/L. Follow-up was systematically performed for the primary endpoint: a composite of sudden cardiac death, heart failure related death, stroke-related death, heart failure hospitalization, hospitalization for stroke, spontaneous sustained ventricular tachycardia (VT) or appropriate ICD discharge, and progression to NYHA class III-IV. Elevated hs-cTnT was present in 33 of 135 (24%) HC patients. During a median follow-up of 5.0 years (IQR: 4.9-5.1) 18 patients reached the primary endpoint. Using Cox regression analysis, elevated hs-cTnT was univariately associated with the primary endpoint (HR: 3.4 (95%CI: 1.4-8.7, p=0.009). Also female sex, previous syncope, previous non-sustained VT, reduced LV ejection fraction (<50%) and CICP were associated with the primary endpoint. In multivariable analysis, elevated hs-cTnT remained independently associated with outcome (aHR: 4.7 (95%CI: 1.8-12.6, p = 0.002). In conclusion, this 5-year follow-up study is the first to prospectively confirm the association of elevated hs-cTnT and adverse outcomes. In addition to established clinical variables, cTn seems the biomarker of interest to further improve risk prediction in HC, which should be evaluated in larger prospective registries.

Cardiac monitoring in HER2-positive patients on trastuzumab treatment: A review and implications for clinical practice.

Trastuzumab prolongs progression-free and overall survival in patients with human epidermal growth factor receptor 2 (HER2) positive breast cancer. However, trastuzumab treatment is hampered by cardiotoxicity, defined as a left ventricular ejection fraction (LVEF) decline with a reported incidence ranging from 3 to 27% depending on variable factors. Early identification of patients at increased risk of trastuzumab-induced myocardial damage is of great importance to prevent deterioration to irreversible cardiotoxicity. Although current cardiac monitoring with multi gated acquisition (MUGA) scanning and/or conventional 2D-echocardiography (2DE) have a high availability, their reproducibility are modest, and more sensitive and reliable techniques are needed such as 3D-echocardiography (3DE) and speckle tracking echocardiography (STE). But which other diagnostic imaging modalities are available for patients before and during trastuzumab treatment? In addition, what is the optimal frequency and duration of cardiac monitoring? At last, which biomarker monitoring strategies are currently available for the identification of cardiotoxicity in patients treated with trastuzumab?

NT-proBNP correlates with LVEF decline in HER2-positive breast cancer patients treated with trastuzumab.

BACKGROUND: Early identification of cardiac dysfunction by non-invasive imaging in HER2-positive breast cancer patients treated with trastuzumab is challenging. In particular multigated acquisition (MUGA) scan, which is most widely used, is unable to detect subclinical cardiac changes. The use of N-terminal pro-brain natriuretic peptide (NT-proBNP), a serum biomarker of myocardial stress, might improve timely diagnosis. METHODS: This prospective, single-center, cohort study included patients with HER2-positive breast cancer who started trastuzumab therapy. Echocardiography was scheduled at regular intervals every 3 months during one year follow-up for cardiac function monitoring. For research purposes, NT-proBNP was determined at the same time points. Trastuzumab-induced cardiotoxicity (TIC) was the primary study endpoint, defined as a left ventricular ejection fraction (LVEF) < 45%, and/or an absolute decline in LVEF > 10% since inclusion, and/or the incidence of a clinical cardiac event. RESULTS: A total of 135 patients were enrolled between April 2008 and June 2016, with a median age of 54 years (IQR: 47-61). By three-dimensional echocardiography (3DE), the median LVEF at baseline was 62% (IQR: 58-65). At a median of 6 months (IQR: 5-11), 45 patients (33%) reached the study endpoint of TIC. Patients with TIC had a mean change of - 9.5% in LVEF (95% CI -7.2 to - 11.7; p = 0.001) during 1 year of trastuzumab treatment. Both NT-proBNP at baseline (HR 1.04, 95% CI 1.02-1.07; p = 0.003) and LVEF decline during anthracycline treatment prior to the start of trastuzumab (HR 1.16, 95% CI 1.07-1.25; p < 0.001) were independently associated with development of TIC. The level of NT-proBNP during follow-up was associated too with development of TIC (HR 1.06 per 10 pmol/l difference, 95% CI 1.02-1.10; p = 0.008). No steadily or sudden increase in NT-proBNP prior to TIC was observed. CONCLUSIONS: NT-proBNP cannot be used as a surrogate monitoring tool for trastuzumab-induced cardiotoxicity in HER2-positive breast cancer patients during the first year of treatment. Patients showing an LVEF decline during anthracycline pre-treatment appeared vulnerable for trastuzumab-induced cardiotoxicity.

Association between Lifelong Physical Activity and Disease Characteristics in HCM.

PURPOSE: Hypertrophic cardiomyopathy (HCM) is characterized by inappropriate left ventricular (LV) wall thickness. Adaptations to exercise can occasionally mimic certain HCM characteristics. However, it is unclear whether physical activity affects HCM genotype expression and disease characteristics. Consequently, we compared lifelong physical activity volumes between HCM gene carriers with and without HCM phenotype, and compared disease characteristics among tertiles of physical activity in phenotypic HCM patients. METHODS: We enrolled n = 22 genotype positive/phenotype negative (G+/P-) HCM gene carriers, n = 44 genotype positive/phenotype positive (G+/P+) HCM patients, and n = 36 genotype negative/phenotype positive (G-/P+) HCM patients. Lifelong physical activity was recorded using a questionnaire and quantified as metabolic equivalent of task hours per week. RESULTS: We included 102 participants (51 ± 16 yr, 49% male). Lifelong physical activity volumes were not different between G+/P+ and G+/P- subjects (16 [10-29] vs 14 [6-26] metabolic equivalent of task-hours per week, P = 0.33). Among phenotypic HCM patients, there was no difference in LV wall thickness, mass, and late gadolinium enhancement across physical activity tertiles. Patients with the highest reported physical activity volumes were younger at the time of diagnosis (tertile 1: 52 ± 14 yr, tertile 2: 49 ± 15 yr, tertile 3: 41 ± 18 yr; P = 0.03), and more often had a history of nonsustained ventricular tachycardia (4% vs 30% vs 30%, P = 0.03). CONCLUSIONS: Lifelong physical activity volumes are not associated with genotype-to-phenotype transition in HCM gene carriers. We also found no difference in LV wall thickness across physical activity tertiles. However, the most active HCM patients were younger at the time of diagnosis and had a higher arrhythmic burden. These observations warrant further exploration of the role of exercise in HCM disease development.

High T2-weighted signal intensity for risk prediction of sudden cardiac death in hypertrophic cardiomyopathy.

In search of improved risk stratification in hypertrophic cardiomyopathy (HCM), CMR imaging has been implicated as a potential tool for prediction of sudden cardiac death (SCD). In follow-up of the promising results with extensive late gadolinium enhancement (LGE), high signal-intensity on T2-weighted imaging (HighT2) has become subject of interest given its association with markers of adverse disease progression, such as LGE, elevated troponin and non-sustained ventricular tachycardia. In lack of follow-up cohorts, we initiated an exploratory study on the association between HighT2 and the internationally defined risk categories of SCD. In a cohort of 109 HCM patients from a multicenter study on CMR imaging and biomarkers, we estimated the 5-year SCD risk (HCM Risk-SCD model). Patients were categorized as low (< 4%), intermediate (≥ 4-<6%) or high (≥ 6%) risk. In addition, risk categorization according to the ACC/AHA guidelines was performed. HighT2 was present in 27% (29/109). Patients with HighT2 were more often at an intermediate-high risk of SCD according to the European (28 vs. 10%, p = .032) and American guidelines (41 vs. 18%, p = .010) compared to those without HighT2. The estimated 5-year SCD risk of our cohort was 1.9% (IQR 1.3-2.9%), and projected SCD rates were higher in patients with than without HighT2 (2.8 vs. 1.8%, p = .002). In conclusion, HCM patients with HighT2 were more likely to be intermediate-high risk, with projected SCD rates that were 1.5 fold higher than in patients without HighT2. These pilot findings call for corroborative studies with more intermediate-high risk HCM patients and clinical follow-up to assess whether HighT2 may have additional value to current risk stratification.

Prediction of Extensive Myocardial Fibrosis in Nonhigh Risk Patients With Hypertrophic Cardiomyopathy.

In nonhigh risk patients with hypertrophic cardiomyopathy (HC), the presence of extensive late gadolinium enhancement (LGEext) at cardiovascular magnetic resonance (CMR) imaging has been proposed as a risk modifier in the decision process for implantable cardioverter defibrillator implantation. With a pretest risk of about 10%, a strategy that alters the likelihood of LGEext could markedly affect efficacious CMR imaging. Our aim was to study the potential of clinical variables and biomarkers to predict LGEext. In 98 HC patients without any clear indication for implantable cardioverter defibrillator implantation, we determined the discriminative values of a set of clinical variables and a panel of biomarkers (hs-cTnT, NTproBNP, GDF-15, and Gal-3, CICP) for LGEext, that is, LGE ≥15% of the left ventricular mass. LGEext was present in 10% (10/98) of patients. The clinical prediction model contained a history of nonsustained ventricular tachycardia, maximal wall thickness and reduced systolic function (c-statistic: 0.868, p <0.001). Of all biomarkers, only hs-cTnT was associated with LGEext, in addition to the improved clinical model of diagnostic accuracy (p = 0.04). A biomarker-only strategy allowed the exclusion of LGEext in half of the cohort, in case of a hs-cTnT concentration less than the optimal cutoff (Youden index; 8 ng/L-sensitivity 100%, specificity 54%). In conclusion, in this nonhigh risk HC cohort, the pretest likelihood of LGEext can be altered using clinical variables and the addition of hs-cTnT. The promising findings with the use of hs-cTnT only call for new initiatives to study its impact on efficacious CMR imaging in a larger HC population, either with or without additional use of clinical variables.

Risk of misclassification with a non-fasting lipid profile in secondary cardiovascular prevention.

AIMS: Routinely fasting is not necessary for measuring the lipid profile according to the latest European consensus. However, LDL-C tends to be lower in the non-fasting state with risk of misclassification. The extent of misclassification in secondary cardiovascular prevention with a non-fasting lipid profile was investigated. METHODS AND RESULTS: 329 patients on lipid lowering therapy for secondary cardiovascular prevention measured a fasting and non-fasting lipid profile. Cut-off values for LDL-C, non-HDL-C and apolipoprotein B were set at <1.8mmol/l, <2.6mmol/l and <0.8g/l, respectively. Study outcomes were net misclassification with non-fasting LDL-C (calculated using the Friedewald formula), direct LDL-C, non-HDL-C and apolipoprotein B. Net misclassification <10% was considered clinically irrelevant. Mean age was 68.3±8.5years and the majority were men (79%). Non-fasting measurements resulted in lower LDL-C (-0.2±0.4mmol/l, P<0.001), direct LDL-C (-0.1±0.2mmol/l, P=0.001), non-HDL-C (-0.1±0.4mmol/l, P=0.004) and apolipoprotein B (-0.02±0.10g/l, P=0.004). 36.0% of the patients reached a fasting LDL-C target of <1.8mmol/l with a significant net misclassification of 10.7% (95% CI 6.4-15.0%) in the non-fasting state. In the non-fasting state net misclassification with direct LDL-C was 5.7% (95% CI 2.1-9.2%), 4.0% (95% CI 1.0-7.4%) with non-HDL-C and 4.1% (95% CI 1.1-9.1%) with apolipoprotein B. CONCLUSION: Use of non-fasting LDL-C as treatment target in secondary cardiovascular prevention resulted in significant misclassification with subsequent risk of undertreatment, whereas non-fasting direct LDL-C, non-HDL-C and apolipoprotein B are reliable parameters.

Sustained improvement after combined anterior mitral leaflet extension and myectomy in hypertrophic obstructive cardiomyopathy.

BACKGROUND: Mitral leaflet extension (MLE) combined with septal myectomy is a new surgical approach to treat hypertrophic obstructive cardiomyopathy (HOCM) and an enlarged mitral leaflet area. The study presents the long-term clinical results and outcome of this technique. METHODS AND RESULTS: MLE entails grafting a glutaraldehyde-preserved autologous pericardial patch onto the center portion of the anterior mitral valve leaflet. Twenty-nine patients with HOCM were studied. Mean follow-up (+/-SD) was 3.4+/-2.1 years (range 3 months to 7.7 years). The preoperative calculated mitral leaflet area was 16.7+/-3.4 cm2. New York Heart Association functional class improved significantly from 2.8+/-0.4 to 1.3+/-0.4 (P<0.05), width of the interventricular septum decreased from 23+/-4 to 17+/-2 mm (P<0.05), left ventricular outflow tract gradient decreased from 100+/-20 to 17+/-14 mm Hg (P<0.01), severity of mitral regurgitation graded on a scale from 0 to 4+ decreased from 2.5+/-0.9 to 0.5+/-0.6 (P<0.01), and severity of the systolic anterior motion of the mitral valve graded on a scale from 0 to 3+ decreased from 2.9+/-0.3 to 0.5+/-0.7 (P<0.01) postoperatively. There were no deaths associated with surgery. CONCLUSIONS: Long-term follow-up shows sustained improvement in functional status, reduction of outflow tract obstruction, and attenuation of mitral regurgitation and systolic anterior motion of the mitral valve. In this respect, the new technique widens the surgical applications in HOCM.

Hypertrophic cardiomyopathy in a large community-based population: clinical outcome and identification of risk factors for sudden cardiac death and clinical deterioration.

OBJECTIVES: This study evaluates the clinical course and identifies risk factors for sudden cardiac death (SCD) and clinical deterioration in hypertrophic cardiomyopathy (HCM) in a large community-based population. Comparison was made with data from six tertiary referral and six nonreferral institutions. BACKGROUND: Hypertrophic cardiomyopathy is a disease with marked heterogeneity in clinical presentation and prognosis. Risk factors for SCD are not well defined in patients free of referral bias. METHODS: Between 1970 and 1999, 225 consecutive patients (mean age [+/-SD] 41+/-16 years) were examined and followed at yearly intervals. RESULTS: Forty-four deaths were recorded of which 27 cases were cardiovascular. Fourteen patients died suddenly, six were successfully resuscitated, and seven patients died of congestive heart failure. The annual mortality, annual cardiac mortality, and annual mortality due to sudden death were 1.3%, 0.8%, and 0.6%, respectively. At least one New York Heart Association (NYHA) functional class deterioration was reported in 33% of the patients with a significant (> or =50 mm Hg) left ventricular outflow tract (LVOT) gradient in contrast to 7% without obstruction. The presence of syncope was related to SCD (p < 0.05). Younger age and more severe functional limitation distinguishes patients from in hospital-based centers from the ones in community-based centers. CONCLUSIONS: Hypertrophic cardiomyopathy is a benign disease in an unselected population with a low incidence of cardiac death. Syncope was associated with a higher incidence of SCD and patients with a significant LVOT obstruction were more susceptible to clinical deterioration.