Clinical research study implementation of case-finding strategies for heart failure and chronic obstructive pulmonary disease in the elderly with reduced exercise tolerance or dyspnea: A cluster randomized trial.

BACKGROUND: Heart failure (HF) and chronic obstructive pulmonary disease (COPD) often remain undiagnosed in older individuals, although both disorders inhibit functionality and impair health. The aim of the study was to assess the effectiveness of a case-finding strategy of these disorders. METHODS: This is a clustered randomized trial; 18 general practices from the vicinity of Utrecht, the Netherlands, were randomly allocated to a case-finding strategy or usual care. Multimorbid community subjects (≥65 years) with dyspnea or reduced exercise tolerance were eligible for inclusion. The case-finding strategy consisted of history taking, physical examination, blood tests, electrocardiography, spirometry, and echocardiography. Subsequent treatment decisions were at the discretion of the general practitioner. Questionnaires regarding health status and functionality were filled out at baseline and after 6 months of follow-up. Information regarding changes in medication and health care use during the 6 months follow-up was extracted. RESULTS: A total of 829 participants were randomized: 389 in the case-finding strategy group and 440 in the usual care group. More patients in the case-finding group received a new diagnosis of HF or COPD than the usual care group (cumulative incidence 34% vs 2% and 17% vs. 2%, respectively). Scores for health status, functionality, and health care use were similar between the 2 strategies after 6 months of follow-up. CONCLUSIONS: A case-finding strategy applied in primary care to multimorbid older people with dyspnea or reduced exercise tolerance resulted in a number of new diagnoses of HF and COPD but did not result in short-term improvement of health status compared to usual care.

Distribution of Estimated 10-Year Risk of Recurrent Vascular Events and Residual Risk in a Secondary Prevention Population.

BACKGROUND: Among patients with clinically manifest vascular disease, the risk of recurrent vascular events is likely to vary. We assessed the distribution of estimated 10-year risk of recurrent vascular events in a secondary prevention population. We also estimated the potential risk reduction and residual risk that can be achieved if patients reach guideline-recommended risk factor targets. METHODS: The SMART score (Second Manifestations of Arterial Disease) for 10-year risk of myocardial infarction, stroke, or vascular death was applied to 6904 patients with vascular disease. The risk score was externally validated in 18 436 patients with various manifestations of vascular disease from the TNT (Treating to New Targets), IDEAL (Incremental Decrease in End Points Through Aggressive Lipid Lowering), SPARCL (Stroke Prevention by Aggressive Reduction in Cholesterol Levels), and CAPRIE (Clopidogrel Versus Aspirin in Patients at Risk of Ischemic Events) trials. The residual risk at guideline-recommended targets was estimated by applying relative risk reductions from meta-analyses to the estimated risk for targets for systolic blood pressure, low-density lipoprotein cholesterol, smoking, physical activity, and use of antithrombotic agents. RESULTS: The external performance of the SMART risk score was reasonable, apart from overestimation of risk in patients with 10-year risk >40%. In patients with various manifestations of vascular disease, median 10-year risk of a recurrent major vascular event was 17% (interquartile range, 11%-28%), varying from <10% in 18% to >30% in 22% of the patients. If risk factors were at guideline-recommended targets, the residual 10-year risk would be <10% in 47% and >30% in 9% of the patients (median, 11%; interquartile range, 7%-17%). CONCLUSIONS: Among patients with vascular disease, there is very substantial variation in estimated 10-year risk of recurrent vascular events. If all modifiable risk factors were at guideline-recommended targets, half of the patients would have a 10-year risk <10%. These data suggest that even with optimal treatment, many patients with vascular disease will remain at >20% and even >30% 10-year risk, clearly delineating an area of substantial unmet medical need.

An easy-to-use scoring index to determine severity of mitral regurgitation by 2D echocardiography in clinical practice.

PURPOSE: Mitral regurgitation (MR) grading by two-dimensional transthoracic echocardiography is challenging, but important to determine the best treatment strategy in patients with MR. Current guidelines advocate an integrative approach, although no recommendation is provided on how to do so. An easy-to-use index will be helpful for standardized and reproducible MR grading. METHODS: Eleven echocardiographic parameters were retrospectively evaluated in 145 patients with moderate or severe MR. Parameters were scored positive or negative for severe MR, where expert panel consensus reading was considered as the reference standard. Logistic regression was performed, and adjusted coefficients were used to create a risk score for severe MR per patient (ROSE-index). The best cutoff with corresponding predictive values was determined. RESULTS: Eighty-two percent of all parameters could be determined. Multivariable analysis revealed five parameters that remained significant predictors for severe MR: morphology, jet characteristics, vena contracta, systolic reversal, and left ventricular dimensions. With different weighing, a total score of 8 could be obtained. Median total ROSE-index score for moderate (2.0) and severe MR (5.0) did significantly differ. The cutoff score (≥4) revealed sensitivity 0.84 and specificity 0.83 to diagnose severe MR. Negative predictive value was 100% for score 0 and 1; score 6-8 showed a 100% positive predictive value. Inter- and intra-observer agreements were excellent (K-values >0.80). CONCLUSION: Here, we propose an easy-to-use tool for integrated analysis of guideline parameters to assess MR severity. Using this so-called ROSE-index revealed reliable and reproducible assessment of severe MR (cutoff≥4) that may be helpful for clinical decision making.

Mutation-positive arrhythmogenic right ventricular dysplasia/cardiomyopathy: the triangle of dysplasia displaced.

INTRODUCTION: The traditional description of the Triangle of Dysplasia in Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy (ARVD/C) predates genetic testing and excludes biventricular phenotypes. METHODS AND RESULTS: We analyzed Cardiac Magnetic Resonance (CMR) studies of 74 mutation-positive ARVD/C patients for regional abnormalities on a 5-segment RV and 17-segment LV model. The location of electroanatomic endo- and epicardial scar and site of successful VT ablation was recorded in 11 ARVD/C subjects. Among 54/74 (73%) subjects with abnormal CMR, the RV was abnormal in almost all (96%), and 52% had biventricular involvement. Isolated LV abnormalities were uncommon (4%). Dyskinetic basal inferior wall (94%) was the most prevalent RV abnormality, followed by basal anterior wall (87%) dyskinesis. Subepicardial fat infiltration in the posterolateral LV (80%) was the most frequent LV abnormality. Similar to CMR data, voltage maps revealed scar (<0.5 mV) in the RV basal inferior wall (100%), followed by the RV basal anterior wall (64%) and LV posterolateral wall (45%). All 16 RV VTs originated from the basal inferior wall (50%) or basal anterior wall (50%). Of 3 LV VTs, 2 localized to the posterolateral wall. In both modalities, RV apical involvement never occurred in isolation. CONCLUSION: Mutation-positive ARVD/C exhibits a previously unrecognized characteristic pattern of disease involving the basal inferior and anterior RV, and the posterolateral LV. The RV apex is only involved in advanced ARVD/C, typically as a part of global RV involvement. These results displace the RV apex from the Triangle of Dysplasia, and provide insights into the pathophysiology of ARVD/C.

Leisure-time and occupational physical activity and health outcomes in cardiovascular disease.

OBJECTIVE: In healthy populations, leisure-time physical activity (LTPA) improves health outcomes, while, paradoxically, occupational physical activity (OPA) is associated with detrimental health effects. This study aimed to investigate the associations of LTPA and OPA with mortality, cardiovascular events and type 2 diabetes (T2D) in patients with cardiovascular disease (CVD). METHODS: In 7058 outpatients with CVD (age 61±10 years, 75% male) from the prospective Utrecht Cardiovascular Cohort-Second Manifestations of ARTerial disease cohort, Cox models were used to quantify the associations between self-reported LTPA and OPA and all-cause mortality, cardiovascular events and T2D. RESULTS: Over 8.6 years (IQR: 4.6-12.5) of follow-up, 1088 vascular events, 1254 deaths and 447 incident T2D cases occurred. The top LTPA quarter had a lower risk of all-cause mortality (HR 0.63, 95% CI 0.54 to 0.74), recurrent cardiovascular events (HR 0.72, 95% CI 0.60 to 0.84) and incident T2D (HR 0.71, 95% CI 0.55 to 0.93), compared with the lowest quarter. The continuous LTPA associations were reverse J-shaped for all-cause mortality and vascular events and linear for T2D. OPA (heavy manual vs sedentary) showed a trend towards an increased risk of all-cause mortality (HR 1.08, 95% CI 0.86 to 1.35), cardiovascular events (HR 1.15, 95% CI 0.91 to 1.45) and T2D (HR 1.04, 95% CI 0.72 to 1.50). The detrimental effects of higher OPA were more pronounced in men, never-smokers, people with higher education and active employment. CONCLUSIONS: In patients with CVD, LTPA was associated with lower risk of all-cause mortality, recurrent cardiovascular events and incident T2D. In contrast, OPA seemed to increase the risk of these outcomes. These findings support the existence of a physical activity paradox in patients with CVD.

Heart failure medication dosage and survival in women and men seen at outpatient clinics.

OBJECTIVE: Women with heart failure with reduced ejection fraction (HFrEF) may reach optimal treatment effect at half of the guideline-recommended medication dose. This study investigates prescription practice and its relation with survival of patients with HF in daily care. METHODS: Electronic health record data from 13 Dutch outpatient cardiology clinics were extracted for HF receiving at least one guideline-recommended HF medication. Dose changes over consecutive prescriptions were modelled using natural cubic splines. Inverse probability-weighted Cox regression was used to assess the relationship between dose (reference≥50% target dose) and all-cause mortality. RESULTS: The study population comprised 561 women (29% HFrEF (ejection fraction (EF)<40%), 49% heart failure with preserved ejection fraction (EF≥50%); HFpEF and 615 men (47% and 25%, respectively). During a median follow-up of 3.7 years, 252 patients died (48% women; 167 HFrEF, 84 HFpEF). Nine hundred thirty-four patients (46% women) received ACE inhibitors (ACEIs) or angiotensin receptor blockers (ARBs), 795 (48% women) beta blockers and 178 (42% women) mineralocorticoid receptor antagonists (MRAs). In both sexes, the mean target dose across prescriptions was 50% for ACEI/ARBs and beta blockers, and 100% for MRAs. ACEI/ARB dose of <50% was associated with lower mortality in women but not in men with HFrEF. This was not seen in patients with HFpEF. Beta-blocker dose was not associated with all-cause mortality. CONCLUSION: Patients with HF seen in outpatient cardiology clinics receive half of the guideline-recommended medication dose. Lower ACEI/ARB dose was associated with improved survival in women with HFrEF. These results underscore the importance of (re)defining optimal medical therapy for women with HFrEF.

Patients with coronary, cerebrovascular or peripheral arterial obstructive disease differ in risk for new vascular events and mortality: the SMART study.

AIMS: Atherosclerosis causes coronary artery disease (CAD), cerebrovascular disease (CVD) or peripheral arterial obstructive disease (PAOD). The risk of new vascular events and mortality is high. Direct comparisons of vascular event rates are scarce. METHODS AND RESULTS: Vascular risk factors and outcome events of 3563 patients from a university hospital presenting with nondisabling CAD, CVD or PAOD were compared with regression analyses, adjusted for age and sex (median follow-up, 3.9 years). The primary outcome was the composite of myocardial infarction, stroke and vascular death. The risk among the three groups of outcomes was compared using the Cox regression analysis. At baseline, CAD patients were the most obese; PAOD patients smoked the most and suffered more often from hypertension and hyperlipidaemia. The average rate of vascular events was 2.5% per year; the hazard ratio (HR) of CVD/CAD was 1.7 [95% confidence interval (CI): 1.3-2.2] and PAOD/CAD was 1.8 (95% CI: 1.5-2.0). PAOD patients had a higher risk for coronary events than CAD (HR: 1.6; 95% CI: 1.2-2.1). Patients with CVD or PAOD had a higher risk for major bleeding than CAD patients (HR: 2.1; 95% CI: 1.4-3.2). CONCLUSION: Patients with a recent CVD or PAOD have almost twice the risk for future vascular events than those with CAD.

A prediction model for left ventricular mass in patients at high cardiovascular risk.

BACKGROUND: Left ventricular (LV) mass has a continuous relation with cardiovascular risk, and regression of LV mass induced by pharmacological treatment is associated with improved prognosis. Therefore, early identification of patients with a large LV mass is desired. We developed a model to predict LV mass in individual hypertensives at high cardiovascular risk. DESIGN AND METHODS: We analyzed data of 536 hypertensives with symptomatic extracardiac atherosclerotic disease or marked risk factors for atherosclerosis from a cross-sectional study in a tertiary referral center. LV mass was measured by cardiac MRI. We developed the prediction rule with multivariable linear regression analysis and stepwise backward elimination. Internal validation was assessed with bootstrap sampling to obtain an estimate of model performance (R²) that may be expected for new patients. RESULTS: Important predictors for LV mass included sex, height, body mass index, systolic blood pressure, and previous aneurysm of the abdominal aorta. R² of the prediction model was 45% after internal validation, which was considerably higher than the R² of previously reported models (range 1-38%). Addition of electrocardiography data showed limited improvement of the model performance (R²=47%). CONCLUSION: We present a prediction model for LV mass in hypertensives at high cardiovascular risk. After external validation, this model may be used in clinical practice to estimate LV mass for early identification of large LV mass. The predictions of the model may support appropriate medical care in the prevention of cardiovascular disease.

Effects of on-pump and off-pump coronary artery bypass grafting on left ventricular relaxation and compliance: a comprehensive perioperative echocardiography study.

AIMS: The short-term effect of coronary artery bypass grafting (CABG) on diastolic function is only moderately investigated. Furthermore, it remains unknown whether avoidance of cardioplegic arrest by an off-pump CABG procedure has advantages over on-pump procedure regarding diastolic relaxation and compliance. We investigated whether components of diastolic function would be improved the day after CABG depending on the type of the surgical procedure. METHODS AND RESULTS: Spontaneously breathing on-pump (n = 20) and off-pump CABG (n = 12) patients underwent a comprehensive transthoracic echocardiography examination the day before and the day after elective CABG, including transmitral and pulmonary vein flow parameters, colour M-mode flow propagation velocity (Vp) and tissue Doppler assessment of the average mitral annulus diastolic velocity (Em). Isovolumic relaxation and E-wave deceleration time were corrected for heart rate (IVRTcHR and DTcHR). Left ventricular (LV) relaxation time (τ) and LV operating stiffness (LVOS) were calculated. Overall and independent from operation type and preload, CABG decreased IVRTcHR (107 ± 20 vs. 93 ± 15 ms) (P < 0.01) and τ (54 ± 10 vs. 45 ± 10 ms) (P < 0.01), increased Vp (49 ± 22 vs. 75 ± 37 cm/s) (P < 0.01), and increased Em (6.6 ± 2.0 vs. 7.3 ± 1.3 cm/s, P = 0.06), indicating improved relaxation. LVOS increased (0.13 ± 0.06 vs. 0.22 ± 0.05 mmHg/mL) (P < 0.01), compatible with an impaired compliance. A similar improvement in relaxation and impairment in compliance were observed in both groups. CONCLUSION: Myocardial relaxation improved the day after CABG irrespective of the use of cardiopulmonary bypass with cardioplegic arrest. Impairment in compliance could not be prevented by the avoidance of cardioplegia.

Normal-range thyroid-stimulating hormone levels and cardiovascular events and mortality in type 2 diabetes.

AIMS: Thyroid dysfunction is a risk factor for cardiovascular disease. Whether thyroid function within the normal range is a risk factor for cardiovascular disease remains uncertain. The aim of this study is to evaluate whether plasma thyroid-stimulating hormone (TSH) levels in the normal range are a risk factor for cardiovascular disease and mortality in participants with type 2 diabetes mellitus with high cardiovascular risk. METHODS: We included 1265 participants with high cardiovascular risk, type 2 diabetes, and TSH within the normal range (0.35-5.00 mIU/L) from the Second Manifestations of ARTerial disease cohort. The primary outcome was major cardiovascular events (MACE; vascular death, stroke and myocardial infarction). Secondary outcomes of interest were the separate vascular outcomes and all-cause mortality. Cox proportional hazard models were used to evaluate the risk of plasma TSH levels on all outcomes. RESULTS: A total of 191 MACE occurred during a total follow-up of 8183 years. Plasma TSH levels were not associated with MACE (hazard ratio (HR) per mIU/L TSH increase 0.93; 95% confidence interval (95%CI) 0.80-1.08). With a total of 54 strokes during the study period, plasma TSH was associated with a lower risk of stroke (HR per mIU/L 0.64, 95% CI 0.45-0.89). There was no association between plasma TSH levels and risk of myocardial infarction, vascular death, or all-cause mortality. CONCLUSIONS: Higher TSH levels within the normal range are associated with a lower risk of stroke in high-risk patients with type 2 diabetes, but not associated with the risk of other cardiovascular events or mortality.

A Change of Heart: Yield of Cardiac Imaging in Acute Stroke Workup.

This case report describes a patient who experienced a recurrent ischemic stroke within 24 h. Dual-energy computed tomography (DECT) angiography on admission showed 2 intracardiac thrombi, 1 in the left ventricle and 1 in the left atrial appendage. Following the second ischemic event, repeated DECT angiography showed that the ventricular thrombus had considerably diminished, suggesting that the recurrent brain infarction was caused by cardioembolism. This case emphasizes (1) the potential benefit of cardiac evaluation through CT angiography in the acute stroke setting, and (2) the use of DECT angiography for the detection of thrombus and the differentiation between thrombus, the myocardial wall, and a slow flow of contrast.

Estimated Life Expectancy Without Recurrent Cardiovascular Events in Patients With Vascular Disease: The SMART-REACH Model.

Background In patients with vascular disease, risk models may support decision making on novel risk reducing interventions, such as proprotein convertase subtilisin/kexin type 9 inhibitors or anti-inflammatory agents. We developed and validated an innovative model to estimate life expectancy without recurrent cardiovascular events for individuals with coronary, cerebrovascular, and/or peripheral artery disease that enables estimation of preventive treatment effect in lifetime gained. Methods and Results Study participants originated from prospective cohort studies: the SMART (Secondary Manifestations of Arterial Disease) cohort and REACH (Reduction of Atherothrombosis for Continued Health) cohorts of 14 259 ( REACH Western Europe), 19 170 ( REACH North America) and 6959 ( SMART , The Netherlands) patients with cardiovascular disease. The SMART-REACH model to estimate life expectancy without recurrent events was developed in REACH Western Europe as a Fine and Gray competing risk model incorporating cardiovascular risk factors. Validation was performed in REACH North America and SMART . Outcomes were (1) cardiovascular events (myocardial infarction, stroke, cardiovascular death) and (2) noncardiovascular death. Predictors were sex, smoking, diabetes mellitus, systolic blood pressure, total cholesterol, creatinine, number of cardiovascular disease locations, atrial fibrillation, and heart failure. Calibration plots showed high agreement between estimated and observed prognosis in SMART and REACH North America. C-statistics were 0.68 (95% confidence interval, 0.67-0.70) in SMART and 0.67 (95% confidence interval, 0.66-0.68) in REACH North America. Performance of the SMART-REACH model was better compared with existing risk scores and adds the possibility of estimating lifetime gained by novel therapies. Conclusions The externally validated SMART-REACH model could be used for estimation of anticipated improvements in life expectancy without recurrent cardiovascular events in individual patients with cardiovascular disease in Western Europe and North America.

Echocardiographic quantification of myocardial function using tissue deformation imaging, a guide to image acquisition and analysis using tissue Doppler and speckle tracking.

Recent developments in the field of echocardiography have allowed the cardiologist to objectively quantify regional and global myocardial function. Regional deformation (strain) and deformation rate (strain-rate) can be calculated non-invasively in both the left and right ventricle, providing information on regional (dys-)function in a variety of clinical settings. Although this promising novel technique is increasingly applied in clinical and preclinical research, knowledge about the principles, limitations and technical issues of this technique is mandatory for reliable results and for implementation both in the clinical as well as the scientific field. In this article, we aim to explain the fundamental concepts and potential clinical applicability of strain and strain-rate for both tissue Doppler imaging (TDI) derived and speckle tracking (2D-strain) derived deformation imaging. In addition, a step-by-step approach to image acquisition and post processing is proposed. Finally, clinical examples of deformation imaging in hypertrophic cardiomyopathy (HCM), cardiac resynchronization therapy (CRT) and arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) are presented.

Cardiac phenotype and long-term prognosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia patients with late presentation.

BACKGROUND: The clinical profile of arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) patients with late presentation is unknown. OBJECTIVE: The purpose of this study was to characterize the genotype, cardiac phenotype, and long-term outcomes of ARVC/D patients with late presentation (age ≥50 years at diagnosis). METHODS: Five hundred two patients with an ARVC/D diagnosis from Johns Hopkins and Utrecht Registries were studied and long-term clinical outcomes ascertained. RESULTS: Late presentation was seen in 104 patients (21%; 38% PKP2 carriers); 3% were ≥65 years at diagnosis. Sustained ventricular tachycardia was the major (43%) mode of presentation in patients with late presentation, whereas cardiac syncope was infrequent (P <.001). Those with late presentation were significantly less likely to harbor a known pathogenic mutation (53%; P = .005), have less precordial T-wave repolarization changes (P <.001), and have lower ventricular ectopy burden (P = .026). Over median 6-year follow-up, 68 patients with late presentation (65%) experienced sustained ventricular arrhythmias, with similar arrhythmia-free survival at 5-year follow up (P = .48). Left ventricular dysfunction and heart failure were seen in 24 (32%) and 15 patients (14%), respectively, without need for cardiac transplantation. In the late presentation cohort, male sex, pathogenic mutation, right ventricular structural disease, lack of family history, and electrophysiologic study inducibility were associated with increased arrhythmic risk. CONCLUSION: One-fifth of all ARVC/D patients present after age 50 years, often with sustained ventricular tachycardia, and are less likely to have prior syncope, ECG changes, ventricular ectopy, or identifiable pathogenic mutation. In ARVC/D, late presentation does not confer a benign prognosis and is associated with high arrhythmic risk.

Unrecognized heart failure and chronic obstructive pulmonary disease (COPD) in frail elderly detected through a near-home targeted screening strategy.

BACKGROUND: Reduced exercise tolerance and dyspnea are common in older people, and heart failure (HF) and chronic obstructive pulmonary disease (COPD) are the main causes. We want to determine the prevalence of previously unrecognized HF, COPD, and other chronic diseases in frail older people using a near-home targeted screening strategy. METHODS: Community-dwelling frail persons aged ≥65 years underwent a 2-step screening strategy. First, they received a questionnaire inquiring about dyspnea and exercise tolerance. Those with exercise intolerance and/or dyspnea were invited to visit their primary care physician's office for a screening program, including medical history taking, physical examination, blood tests, electrocardiography, spirometry, and echocardiography. The final diagnosis of every patient was determined by a panel consisting of 3 physicians. RESULTS: Of the 570 elderly who filled out the questionnaire, 395 (69%) had reduced exercise tolerance or dyspnea. Of these, 389 underwent the screening program: 127 (33.5%, 95% confidence interval, 28.9-38.4%) were newly diagnosed with HF (mainly HF with a preserved ejection fraction [23.5%]), and previously unrecognized COPD was detected in 16.8% (95% confidence interval, 13.4-20.9%). In total, 165 patients (43.9%) received a new diagnosis of either HF, COPD, or both. Other new diagnoses (in 32.7% of the screening program patients) included atrial fibrillation (1.8%), valvular disease (21.4%), (persisting) asthma (3.1%), anemia (12.7%), and thyroid disease (0.6%). No clear explanation for the complaints of 47 patients (12.2%) was found using our strategy. CONCLUSION: Unrecognized chronic diseases might be detected in community-dwelling frail elderly using a near-home screening strategy that is simple to implement. It remains to be proven, however, whether optimizing treatment of the newly detected diagnoses in this fragile population with multimorbidities and polypharmacy improves quality of life and reduces morbidity and mortality.

Low high-density lipoprotein cholesterol is not a risk factor for recurrent vascular events in patients with vascular disease on intensive lipid-lowering medication.

OBJECTIVES: This study sought to evaluate the vascular risk of low high-density lipoprotein-cholesterol (HDL-C) in relation to the use and intensity of lipid-lowering medication in patients with clinically manifest vascular diseases. BACKGROUND: Low levels of HDL-C are associated with an increased risk for vascular diseases and may contribute to residual vascular risk in patients already treated for other risk factors. However, post-hoc analyses from statin trials indicate that the vascular risk associated with low HDL-C may be low or even absent in patients using intensive statin therapy. METHODS: We performed a prospective cohort study of 6,111 patients with manifest vascular disease. Cox proportional hazards models were used to evaluate the risk of HDL-C on vascular events in patients using no, usual dose, or intensive lipid-lowering therapy. RESULTS: New vascular events (myocardial infarction, stroke, or vascular death) occurred in 874 subjects during a median follow-up of 5.4 years (interquartile range: 2.9 to 8.6 years). In patients not using lipid-lowering medication at baseline (n = 2,153), a 0.1 mmol/l increase in HDL-C was associated with a 5% reduced risk for all vascular events (hazard ratio [HR]: 0.95; 95% confidence interval [CI]: 0.92 to 0.99). In patients on usual dose lipid-lowering medication (n = 1,910) there was a 6% reduced risk (HR: 0.94; 95% CI: 0.90 to 0.98). However, in patients using intensive lipid-lowering treatment (n = 2,046), HDL-C was not associated with recurrent vascular events (HR: 1.02; 95% CI: 0.98 to 1.07) irrespective of low-density lipoprotein cholesterol level. CONCLUSIONS: In patients with clinically manifest vascular disease using no or usual dose lipid-lowering medication, low plasma HDL-C levels are related to increased vascular risk, whereas in patients using intensive lipid-lowering medication, HDL-C levels are not related to vascular risk.

Early detection of regional functional abnormalities in asymptomatic ARVD/C gene carriers.

BACKGROUND: The overt stage of arrhythmogenic right ventricular (RV) dysplasia/cardiomyopathy (ARVD/C) is preceded by a concealed stage with minor or no signs of disease. However, sudden death may occur in this early phase. Deformation imaging may contribute to early diagnosis. The aims of this study were to compare the diagnostic accuracy of the conventional (1994) versus the recently published (2010) new echocardiographic criteria for ARVD/C and to evaluate the additional value of echocardiographic tissue deformation imaging to detect subclinical RV functional abnormalities in asymptomatic carriers of pathogenic ARVD/C mutations. METHODS: Fourteen asymptomatic first-degree relatives of ARVD/C probands (the ARVD/C-r group; mean age, 38.0 ± 13.2 years) with a pathogenic plakophilin-2 mutation and a group of age-matched controls (n = 56; mean age, 38.2 ± 12.7 years) were included at a 1:4 ratio. A complete echocardiographic evaluation (dimensions, global systolic parameters, and visual assessment and deformation imaging of the RV free wall including Doppler tissue imaging and two-dimensional strain echocardiography) was obtained. Peak systolic strain less negative than -18% and/or postsystolic shortening (postsystolic index > 15%) in any RV segment was considered abnormal. RESULTS: RV dimensions in the ARVD/C-r group were similar to those in controls (RV outflow tract, 15.4 ± 2.9 vs 14.4 ± 1.9 mm/m(2), P = NS; RV inflow tract, 18.6 ± 2.6 vs 19.1 ± 2.6 mm/m(2), P = NS), and global systolic parameters were moderately reduced (tricuspid annular plane systolic excursion, 20.0 ± 3.2 vs 23.9 ± 2.8 mm, P = .001; RV fractional area change, 40.3 ± 8.4 vs 40.6 ± 7.1, P = NS). According to task force criteria, 57% of the ARVD/C-r group and 29% of controls were classified as abnormal when applying the 1994 criteria and 29% and 4% when applying the 2010 criteria, respectively. Doppler tissue imaging and two-dimensional strain deformation (and strain rate) values were reduced in the ARVD/C-r group in the basal and mid RV segments compared with controls (P < .001). In the ARVD/C-r group, peak systolic strain less negative than -18% was seen in six patients (43%), postsystolic strain in nine (64%), and either abnormality in 10 (71%), almost exclusively in the basal segment; these findings were observed in none of the controls. CONCLUSIONS: The 2010 criteria for ARVD/C improve specificity, whereas sensitivity is significantly reduced in this asymptomatic population. In contrast, echocardiographic deformation imaging detects functional abnormalities in the subtricuspid region in 71% of asymptomatic carriers of a pathogenic plakophilin-2 mutation, while regional deformation was normal in all control subjects, indicating superiority of both sensitivity and specificity with these new modalities.

Relation between abdominal obesity, insulin resistance and left ventricular hypertrophy diagnosed by electrocardiogram and magnetic resonance imaging in hypertensive patients.

Obesity is related to left ventricular hypertrophy (LVH). Whether LVH on electrocardiography (ECG-LVH) is a result of increased cardiac electrical activity or due to increased left ventricular mass (LVM) remains to be determined. The aims of the present study were to investigate the relation between obesity and ECG-LVH and LVM by magnetic resonance imaging (MRI-LVM) in patients with hypertension and to investigate the relation of insulin resistance (IR) and LVH. Patients with hypertension (n = 421) were evaluated using Sokolow-Lyon voltage, Cornell voltage, and cardiac magnetic resonance imaging. Waist circumference was used as a measure of abdominal obesity. Linear regression analysis revealed an inverse relation (adjusted ß = -0.02, 95% confidence interval -0.02 to -0.01) between waist circumference and Sokolow-Lyon voltage, indicating a decrease of 0.02 mV per 1-cm increase in waist circumference. There was a positive relation between waist circumference and MRI-LVM (ß = 0.49, 95% confidence interval 0.32 to 0.67). Patients in the highest quartile of LVM had a worse metabolic profile than patients with the Sokolow-Lyon voltage criterion. The relations of IR with ECG-LVH and MRI-LVM were similar to those of waist circumference in relation to ECG-LVH and MRI-LVM. In conclusion, there is an inverse relation between waist circumference and ECG-LVH and a positive relation between waist circumference and MRI-LVM. This study indicates that obesity has a different relation to voltage criteria for LVH compared to anatomic criteria for LVH, supporting the hypothesis that IR decreases electrocardiographic voltages, despite an increase in MRI-LVM. The clinical implication is that especially in patients with IR, Sokolow-Lyon voltage is low in contrast to high MRI-LVM.

Advanced measurement techniques of regional myocardial function to assess the effects of cardiac regenerative therapy in different models of ischaemic cardiomyopathy.

Cardiac regenerative therapy is still not used in daily clinical practice. A reason for this might be the modest effect on relevant global clinical endpoints [i.e. ejection fraction (EF)] in preclinical studies. To introduce proper improvement strategies, it is important to extend the focus from clinical endpoints to more detailed local measures of cardiac function. In this review, we discuss the measurement principles of all invasive and non-invasive techniques that are used to assess the local effects of cardiac regenerative therapy in order to improve feedback to researchers unravelling the dominant pathways that lead to effective cardiac regeneration. Generally adopted mechanisms of cardiac regenerative therapy are: (i) vasculogenesis, (ii) cardiomyogenesis, and (iii) matrix-assisted myocardium stabilization. Since direct in vivo measures of these mechanisms do not exist, we discuss the measurement techniques of local microvascular resistance, myocardial perfusion, viability, fibrosis, and deformation imaging. The ability of these techniques to reflect the mechanism of cardiac regenerative therapy, and the results of applications in stem cell studies are discussed, and critically commented upon. Special attention is given to applications of deformation imaging, since this has recently been suggested and used as a potential new technique to assess local changes of cardiac biomechanics, which requires special knowledge about cardiac physiology. We conclude that besides the clinically relevant EF measurements, detailed measures of local cardiac function provide information about the local changes induced by cardiac regenerative therapy. In particular, combination of deformation imaging, by ultrasound or magnetic resonance imaging, with simultaneously measured local geometry and pressure measurements is a promising approach to assess the effects of cardiac regenerative therapy on local cardiac biomechanics. This approach provides information about local tissue contractility, stiffness, and thereby remodelling. We recommend that researchers use this comprehensive approach in future studies.