Noninvasive Left Ventricular Myocardial Work in Patients with Chronic Aortic Regurgitation and Preserved Left Ventricular Ejection Fraction.

BACKGROUND: Left ventricular (LV) global longitudinal strain (GLS) has been proposed as a sensitive marker of myocardial damage in patients with chronic severe aortic regurgitation (AR) and preserved LV ejection fraction (LVEF). However, LV GLS does not take into account the afterload. Noninvasive LV myocardial work is a novel parameter of LV myocardial performance, which integrates measurements of myocardial deformation and noninvasive blood pressure (afterload). The aims of this study were (1) to assess noninvasive LV myocardial work in patients with chronic AR and preserved LVEF and its correlation with other echocardiographic parameters, (2) to evaluate changes of LV myocardial work after aortic valve replacement or repair (AVR), and (3) to assess the relationship between LV myocardial work and postoperative LV reverse remodeling. METHODS: Fifty-seven patients (53 ± 16 years; 67% men) with moderate or severe chronic AR and preserved LVEF treated by AVR were included. Noninvasive LV myocardial work indices were measured at baseline and postoperatively (between 2 and 12 months after surgery) and compared with previously reported normal reference ranges. RESULTS: Based on normal reference values, patients with chronic AR and preserved LVEF had preserved or increased values of LV global work index (GWI; 82% and 18%, respectively) and LV global constructive work (GCW; 74% and 25%, respectively) and preserved LV global work efficiency (GWE). Left ventricular GWI and GCW showed a positive correlation with markers of AR severity and parameters of LV systolic function. Left ventricular GWI, GCW, and GWE decreased after AVR (P < .001), without changes in LV global wasted work (P = .28). The postoperative impairment of LV GWI, observed in 28% of patients, was closely associated with reduced LV reverse remodeling. CONCLUSIONS: Noninvasive myocardial work may allow better understanding of myocardial function and energetics than afterload-dependent echocardiographic parameters in chronic AR with preserved LVEF.

Right ventricular myocardial work: proof-of-concept for non-invasive assessment of right ventricular function.

AIMS: Right ventricular myocardial work (RVMW) is a novel method for non-invasive assessment of right ventricular (RV) function utilizing RV pressure-strain loops. This study aimed to explore the relationship between RVMW and invasive indices of right heart catheterization (RHC) in a cohort of patients with heart failure with reduced left ventricular ejection fraction (HFrEF), and to compare values of RVMW with those of a group of patients without cardiovascular disease. METHODS AND RESULTS: Non-invasive analysis of RVMW was performed in 22 HFrEF patients [median age 63 (59-67) years] who underwent echocardiography and invasive RHC within 48 h. Conventional RV functional measurements, RV global constructive work (RVGCW), RV global work index (RVGWI), RV global wasted work (RVGWW), and RV global work efficiency (RVGWE) were analysed and compared with invasively measured stroke volume and stroke volume index. Non-invasive analysis of RVMW was also performed in 22 patients without cardiovascular disease to allow for comparison between groups. None of the conventional echocardiographic parameters of RV systolic function were significantly correlated with stroke volume or stroke volume index. In contrast, one of the novel indices derived non-invasively by pressure-strain loops, RVGCW, demonstrated a moderate correlation with invasively measured stroke volume and stroke volume index (r = 0.63, P = 0.002 and r = 0.59, P = 0.004, respectively). RVGWI, RVGCW, and RVGWE were significantly lower in patients with HFrEF compared to a healthy cohort, while values of RVGWW were significantly higher. CONCLUSION: RVGCW is a novel parameter that provides an integrative analysis of RV systolic function and correlates more closely with invasively measured stroke volume and stroke volume index than other standard echocardiographic parameters.

Effect of Smartphone-Enabled Health Monitoring Devices vs Regular Follow-up on Blood Pressure Control Among Patients After Myocardial Infarction: A Randomized Clinical Trial.

Importance: Smart technology via smartphone-compatible devices might improve blood pressure (BP) regulation in patients after myocardial infarction. Objectives: To investigate whether smart technology in clinical practice can improve BP regulation and to evaluate the feasibility of such an intervention. Design, Setting, and Participants: This study was an investigator-initiated, single-center, nonblinded, feasibility, randomized clinical trial conducted at the Department of Cardiology of the Leiden University Medical Center between May 2016 and December 2018. Two hundred patients, who were admitted with either ST-segment elevation myocardial infarction or non-ST-segment acute coronary syndrome, were randomized in a 1:1 fashion between follow-up groups using smart technology and regular care. Statistical analysis was performed from January 2019 to March 2019. Interventions: For patients randomized to regular care, 4 physical outpatient clinic visits were scheduled in the year following the initial event. In the intervention group, patients were given 4 smartphone-compatible devices (weight scale, BP monitor, rhythm monitor, and step counter). In addition, 2 in-person outpatient clinic visits were replaced by electronic visits. Main Outcomes and Measures: The primary outcome was BP control. Secondary outcomes, as a parameter of feasibility, included patient satisfaction (general questionnaire and smart technology-specific questionnaire), measurement adherence, all-cause mortality, and hospitalizations for nonfatal adverse cardiac events. Results: In total, 200 patients (median age, 59.7 years [interquartile range, 52.9-65.6 years]; 156 men [78%]) were included, of whom 100 were randomized to the intervention group and 100 to the control group. After 1 year, 79% of patients in the intervention group had controlled BP vs 76% of patients in the control group (P = .64). General satisfaction with care was the same between groups (mean [SD] scores, 82.6 [14.1] vs 82.0 [15.1]; P = .88). The all-cause mortality rate was 2% in both groups (P > .99). A total of 20 hospitalizations for nonfatal adverse cardiac events occurred (8 in the intervention group and 12 in the control group). Of all patients, 32% sent in measurements each week, with 63% sending data for more than 80% of the weeks they participated in the trial. In the intervention group only, 90.3% of patients were satisfied with the smart technology intervention. Conclusions and Relevance: These findings suggest that smart technology yields similar percentages of patients with regulated BP compared with the standard of care. Such an intervention is feasible in clinical practice and is accepted by patients. More research is mandatory to improve patient selection of such an intervention. Trial Registration: ClinicalTrials.gov Identifier: NCT02976376.

Defining Subclinical Myocardial Dysfunction and Implications for Patients With Diabetes Mellitus and Preserved Ejection Fraction.

Left ventricular (LV) global longitudinal strain (GLS) can detect subclinical myocardial systolic dysfunction in individuals with diabetes. The present study investigates the clinical usefulness and incremental net benefit of identifying subclinical myocardial systolic dysfunction in individuals with diabetes. A cohort of 397 type 2 diabetic individuals was followed up for the occurrence of all-cause mortality. Clinical and echocardiographic data of diabetic patients were assessed retrospectively. LV GLS was evaluated on transthoracic echocardiography using speckle tracking imaging. Subclinical LV systolic dysfunction was defined as LV GLS > -17.0% from 104 healthy volunteers recruited from the community. A total of 178 (44.8%) diabetic individuals had evidence of subclinical LV systolic dysfunction and 46 (11.6%) died during follow-up. The presence of subclinical LV systolic dysfunction was independently associated with all-cause mortality on follow-up (hazard ratio [HR] 2.83, 95% confidence interval [CI] 1.40 to 5.71, p = 0.004). Diabetic individuals without subclinical LV systolic dysfunction had similar survival as the general population (standardized mortality ratio 0.94, 95% CI 0.52 to 1.58). Decision curve analysis showed identification of subclinical LV systolic dysfunction and quantification of LV GLS provided an incremental net clinical benefit at risk stratifying patients for risk of death at 5 years. In conclusion, subclinical LV systolic dysfunction is independently associated with all-cause mortality in diabetic patients. Decision curve analyses suggest use of LV GLS and identification of subclinical LV systolic dysfunction is clinically useful, and provided incremental net clinical benefit for diabetic individuals.

Implementation of smart technology to improve medication adherence in patients with cardiovascular disease: is it effective?

INTRODUCTION: Medication adherence is of key importance in the treatment of cardiovascular disease. Studies consistently show that a substantial proportion of patients is non-adherent. AREAS COVERED: For this review, telemedicine solutions that can potentially improve medication adherence in patients with cardiovascular disease were reviewed. A total of 475 PubMed papers were reviewed, of which 74 were assessed. EXPERT COMMENTARY: Papers showed that evidence regarding telemedicine solutions is mostly conflictive. Simple SMS reminders might work for patients who do not take their medication because of forgetfulness. Educational interventions and coaching interventions, primarily delivered by telephone or via a web-based platform can be effective tools to enhance medication adherence. Finally, it should be noted that current developments in software engineering may dramatically change the way non-adherence is addressed in the nearby future.

Inter-ethnic differences in valve morphology, valvular dysfunction, and aortopathy between Asian and European patients with bicuspid aortic valve.

Background: Transcatheter aortic valve replacement (TAVR) has been shown safe and feasible in patients with bicuspid aortic valve (BAV) morphology. Evaluation of inter-ethnic differences in valve morphology and function and aortic root dimensions in patients with BAV is important for the worldwide spread of this therapy in this subgroup of patients. Comparisons between large European and Asian cohorts of patients with BAV have not been performed, and potential differences between populations may have important implications for TAVR. Aim: The present study evaluated the differences in valve morphology and function and aortic root dimensions between two large cohorts of European and Asian patients with BAV. Methods and results: Aortic valve morphology was defined on transthoracic echocardiography according to the number of commissures and raphe: type 0 = no raphe and two commissures, type 1 = one raphe and two commissures, type 2 = two raphes and one commissure. Aortic stenosis and regurgitation were graded according to current recommendations. For this study, aortic root dimensions were manually measured on transthoracic echocardiograms at the level of the aortic annulus, sinus of Valsalva (SOV), sinotubular junction (STJ), and ascending aorta (AA). Of 1427 patients with BAV (45.2 ± 18.1 years, 71.9% men), 794 (55.6%) were Europeans and 633 (44.4%) were Asians. The groups were comparable in age and proportion of male sex. Asians had higher prevalence of type 1 BAV with raphe between right and non-coronary cusps than Europeans (19.7% vs. 13.6%, respectively; P < 0.001), whereas the Europeans had higher prevalence of type 0 BAV (two commissures, no raphe) than Asians (14.5% vs. 6.8%, respectively; P < 0.001). The prevalence of moderate and severe aortic regurgitation was higher in Europeans than Asians (44.2% vs. 26.8%, respectively; P < 0.001) whereas there were no differences in BAV with normal function or aortic stenosis. After adjusting for demographics, comorbidities, and valve function, the dimensions of the aortic annulus [mean difference 1.17 mm/m2, 95% confidence interval (CI) 0.96-1.39], SOV (mean difference 1.86 mm/m2, 95% CI 1.47-2.24), STJ (mean difference 0.52 mm/m2, 95% CI 0.14-0.90) and AA (mean difference 1.05 mm/m2, 95% CI 0.57-1.52) were significantly larger among Asians compared with Europeans. Conclusions: This large multicentre registry reports for the first time that Asians with BAV showed more frequently type 1 BAV (with fusion between right and non-coronary cusp) and have larger aortic dimensions than Europeans. These findings have important implications for prosthesis type and size selection for TAVR.

Comparison of the diagnostic accuracy of four smartphone-compatible blood pressure monitors in post-myocardial infarction patients.

Introduction Smartphone-compatible blood pressure devices may be a good alternative to enable self-measurement of blood pressure by patients. Furthermore, automatic transferral of data to the hospital allows for remote monitoring. To our knowledge, no study has compared four of these smartphone-compatible blood pressure devices. Methods Patients who were followed up for acute myocardial infarction were asked to participate during their outpatient clinic visit. After five minutes of rest, six blood pressure devices were applied. The order was randomised. Four devices were smartphone-compatible. One device was an automated oscillometric device. One device was a handheld aneroid sphygmomanometer (reference device). All measurements were compared using a linear mixed model. Results A total of 43 patients (62.7 ± 11.3 years, 79% male) were included. Compared to the reference device, four blood pressure monitors yielded a significant higher mean systolic blood pressure and four monitors yielded a significant higher diastolic BP. One device yielded a non-significant lower mean systolic blood pressure and one device yielded a non-significant higher mean diastolic blood pressure. Except for one blood pressure device, all mean differences were smaller than 5 mmHg. Conclusion In this study, average inter-device variability was shown to be statistically significant, however four devices remained within the predefined range of 5 mmHg for both systolic and diastolic blood pressures.

Mobile phones in cryptogenic strOke patients Bringing sIngle Lead ECGs for Atrial Fibrillation detection (MOBILE-AF): study protocol for a randomised controlled trial.

BACKGROUND: Recently published randomised clinical trials indicate that prolonged electrocardiom (ECG) monitoring might enhance the detection of paroxysmal atrial fibrillation (AF) in cryptogenic stroke or transient ischaemic attack (TIA) patients. A device that might be suitable for prolonged ECG monitoring is a smartphone-compatible ECG device (Kardia Mobile, Alivecor, San Francisco, CA, USA) that allows the patient to record a single-lead ECG without the presence of trained health care staff. The MOBILE-AF trial will investigate the effectiveness of the ECG device for AF detection in patients with cryptogenic stroke or TIA. In this paper, the rationale and design of the MOBILE-AF trial is presented. METHODS: For this international, multicentre trial, 200 patients with cryptogenic stroke or TIA will be randomised. One hundred patients will receive the ECG device and will be asked to record their ECG twice daily during a period of 1 year. One hundred patients will receive a 7-day Holter monitor. DISCUSSION: The primary outcome of this study is the percentage of patients in which AF is detected in the first year after the index ischaemic stroke or TIA. Secondary outcomes include markers for AF prediction, orally administered anticoagulation therapy changes, as well as the incidence of recurrent stroke and major bleeds. First results can be expected in mid-2019. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT02507986 . Registered on 15 July 2015.

Chance of surgery in adult congenital heart disease.

Background Young patients with congenital heart disease reaching adulthood face mandatory transition to adult cardiology. Their new cardiologist needs to assess the chances of major future events such as surgery. Using a large national registry, we assessed if patient characteristics at the age of 18 years could predict the chance of congenital heart surgery in adulthood. Design and methods Of 10,300 patients from the CONCOR national registry, we used general patient characteristics at age 18 years, underlying congenital heart defect, history of complications, and interventions in childhood as potential predictors of congenital heart surgery occurring from age 18 years up to age 40 and 60 years. Cox regression was used to calculate hazard ratios with 95% confidence intervals. Analyses were performed separately for all congenital heart surgery and for valvular surgery alone. Results Altogether 2427 patients underwent congenital heart surgery after age 18 years, 1389 of whom underwent valvular surgery. Underlying heart defect, male sex, multiple defects, childhood endocarditis, supraventricular arrhythmia, aortic complications and paediatric cardiovascular surgery, independently predicted adult congenital heart surgery. The mean chance of congenital heart surgery was 22% up to age 40 and 43% up to age 60 years; individual chances spanned from 9-68% up to age 40 and from 19-93% up to age 60 years. Conclusion At the time of transition from paediatric to adult cardiology, an easily obtainable set of characteristics of patients with congenital heart disease can meaningfully inform cardiologists about the patient's individual chance of surgery in adulthood. Our findings warrant validation in other cohorts.

Sex Differences in Phenotypes of Bicuspid Aortic Valve and Aortopathy: Insights From a Large Multicenter, International Registry.

BACKGROUND: This large multicenter, international bicuspid aortic valve (BAV) registry aimed to define the sex differences in prevalence, valve morphology, dysfunction (aortic stenosis/regurgitation), aortopathy, and complications (endocarditis and aortic dissection). METHODS AND RESULTS: Demographic, clinical, and echocardiographic data at first presentation of 1992 patients with BAV (71.5% men) were retrospectively analyzed. BAV morphology and valve function were assessed; aortopathy configuration was defined as isolated dilatation of the sinus of Valsalva or sinotubular junction, isolated dilatation of the ascending aorta distal to the sinotubular junction, or diffuse dilatation of the aortic root and ascending aorta. New cases of endocarditis and aortic dissection were recorded. There were no significant sex differences regarding BAV morphology and frequency of normal valve function. When presenting with moderate/severe aortic valve dysfunction, men had more frequent aortic regurgitation than women (33.8% versus 22.2%, P<0.001), whereas women were more likely to have aortic stenosis (34.5% versus 44.1%, P<0.001). Men had more frequently isolated dilatation of the sinus of Valsalva or sinotubular junction (14.2% versus 6.7%, P<0.001) and diffuse dilatation of the aortic root and ascending aorta (16.2% versus 7.3%, P<0.001) than women. Endocarditis (4.5% versus 2.5%, P=0.037) and aortic dissections (0.5% versus 0%, P<0.001) occurred more frequently in men. CONCLUSIONS: Although there is a male predominance among patients with BAV, men with BAV had more frequently moderate/severe aortic regurgitation at first presentation compared with women, whereas women presented more often with moderate/severe aortic stenosis compared with men. Furthermore, men had more frequent aortopathy than women.

Prognostic Implications of Raphe in Bicuspid Aortic Valve Anatomy.

Importance: Little is known about the association between bicuspid aortic valve (BAV) morphologic findings and the degree of valvular dysfunction, presence of aortopathy, and complications, including aortic valve surgery, aortic dissection, and all-cause mortality. Objective: To investigate the association between BAV morphologic findings (raphe vs nonraphe) and the degree of valve dysfunction, presence of aortopathy, and prognosis (including need for aortic valve surgery, aortic dissection, and all-cause mortality). Design, Setting, and Participants: In this large international multicenter registry of patients with BAV treated at tertiary referral centers, 2118 patients with BAV were evaluated. Patients referred for echocardiography from June 1, 1991, through November 31, 2015, were included in the study. Exposures: Clinical and echocardiographic data were analyzed retrospectively. The morphologic BAV findings were categorized according to the Sievers and Schmidtke classification. Aortic valve function was divided into normal, regurgitation, or stenosis. Patterns of BAV aortopathy included the following: type 1, dilation of the ascending aorta and aortic root; type 2, isolated dilation of the ascending aorta; and type 3, isolated dilation of the sinus of Valsalva and/or sinotubular junction. Main Outcomes and Measures: Association between the presence and location of raphe and the risk of significant (moderate and severe) aortic valve dysfunction and aortic dilation and/or dissection. Results: Of the 2118 patients (mean [SD] age, 47 [18] years; 1525 [72.0%] male), 1881 (88.8%) had BAV with fusion raphe, whereas 237 (11.2%) had BAV without raphe. Bicuspid aortic valves with raphe had a significantly higher prevalence of valve dysfunction, with a significantly higher frequency of aortic regurgitation (622 [33.1%] vs 57 [24.1%], P < .001) and aortic stenosis (728 [38.7%] vs 51 [21.5%], P < .001). Furthermore, aortic valve replacement event rates were significantly higher among patients with BAV with raphe (364 [19.9%] at 1 year, 393 [21.4%] at 2 years, and 447 [24.4%] at 5 years) vs patients without raphe (30 [14.0%] at 1 year, 32 [15.0%] at 2 years, and 40 [18.0%] at 5 years) (P = .02). In addition, the all-cause mortality event rates were significantly higher among patients with BAV with raphe (77 [5.1%] at 1 year, 87 [6.2%] at 2 years, and 110 [9.5%] at 5 years) vs patients without raphe (2 [1.8%] at 1 year, 3 [3.0%] at 2 years, and 5 [4.4%] at 5 years) (P = .03). However, on multivariable analysis, the presence of raphe was not significantly associated with all-cause mortality. Conclusions and Relevance: In this large multicenter, international BAV registry, the presence of raphe was associated with a higher prevalence of significant aortic stenosis and regurgitation. The presence of raphe was also associated with increased rates of aortic valve and aortic surgery. Although patients with BAV and raphe had higher mortality rates than patients without, the presence of a raphe was not independently associated with increased all-cause mortality.

Cardiac Resynchronization Therapy in CKD Stage 4 Patients.

BACKGROUND AND OBJECTIVES: Cardiac resynchronization therapy (CRT) is a well established heart failure treatment that has shown to improve renal function. However, landmark CRT trials excluded patients with severe renal dysfunction. Therefore, this study evaluated the effect of CRT on renal function and long-term prognosis in patients with stage 4 CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This study evaluated 73 consecutive CRT patients (71±10 years) with stage 4 CKD who underwent echocardiographic and renal function evaluation at baseline and 6-month follow-up between 2000 and 2012. As a control group, 18 patients with stage 4 CKD who received an implantable cardioverter defibrillator (ICD) were selected. CRT recipients with ≥15% reduction in left ventricular end-systolic volume at 6-month follow-up were classified as CRT responders. During long-term follow-up (median, 33 months), appropriate defibrillator therapy, heart failure hospitalizations, and all-cause mortality (combined end point) were recorded. RESULTS: At 6-month follow-up, a significant reduction in left ventricular end-systolic volume was observed in CRT patients compared with patients with ICD (from 159±78 to 145±78 ml in CRT patients and from 126±54 to 119±49 ml in ICD patients; P=0.05), and CRT response was observed in 22 patients (30%). Compared with ICD patients, eGFR improved among CRT patients (from 25±4 to 30±9 ml/min per 1.73 m(2); interaction time and group, P=0.04) and was more pronounced among CRT responders (25±3 to 34±9 ml/min per 1.73 m(2); P<0.001). The combined end point was observed in 17 ICD and 62 CRT patients. CRT patients showed superior survival compared with ICD patients (log-rank P=0.03). More importantly, CRT response was independently associated with improved survival free from the combined end point (hazard ratio, 0.51; 95% confidence interval, 0.27 to 0.98; P=0.04) after adjustment for clinical and echocardiographic parameters. CONCLUSIONS: Response to CRT occurs in approximately 30% of patients with stage 4 CKD, which is less than in the average CRT population. CRT was associated with better clinical outcome, and particularly, CRT response was associated with improvement in eGFR and better long-term prognosis.

Super-responders to cardiac resynchronization therapy remain at risk for ventricular arrhythmias and benefit from defibrillator treatment.

AIMS: Mortality and ventricular arrhythmias are reduced in patients responding to cardiac resynchronization therapy (CRT). This response is accompanied by improvement in LVEF, and some patients even outgrow original eligibility criteria for implantable cardioverter-defibrillator (ICD) implantation. It is however unclear if these patients still benefit from ICD treatment. The current study aimed to evaluate if the incidence of ICD therapy is related to the extent of CRT response. METHODS AND RESULTS: All patients who underwent primary prevention CRT-defibrillator implantation were included. They were divided into subgroups according to the reduction in LV end-systolic volume (LVESV) 6 months after implantation. Pre-defined subgroups were: negative responders (increased LVESV), non-responders (decreased LVESV 0-14%), responders (decreased LVESV 15-29%), and super-responders (decreased LVESV ≥30%). During a median follow-up of 57 months (25th-75th percentile 39-84), 512 patients were studied [101 (20%) negative responders, 101 (20%) non-responders, 149 (29%) responders, and 161 (31%) super-responders]. In the first year of follow-up super-responders received significantly less appropriate ICD therapy (3% vs. 12%; P < 0.001). The 5-year cumulative incidence of appropriate ICD therapy was 31% [95% confidence interval (CI) 19-43] in negative responders, 39% (95% CI 25-53) in non-responders, 34% (95% CI 25-43) in responders, and 27% (95% CI 18-35) in super-responders, respectively (p = 0.13). CONCLUSIONS: The extent of CRT response was associated with a parallel reduction of appropriate device therapy during the first year of follow-up. Thereafter, no association was observed. Furthermore, 23% of super-responders were treated for potentially life-threatening arrhythmias and benefit from ICD treatment.

Left ventricular reverse remodeling, device-related adverse events, and long-term outcome after cardiac resynchronization therapy in the elderly.

BACKGROUND: Limited data are available on efficacy, safety, and long-term prognosis after cardiac resynchronization therapy (CRT) in elderly patients. We aimed at evaluating the effect of CRT, device-related adverse events, and long-term outcome after CRT among elderly patients. METHODS AND RESULTS: A total of 798 CRT recipients (208 elderly: age, ≥75 years; 590 nonelderly: age, <75 years) underwent clinical and echocardiographic evaluation at baseline and 6-month follow-up. Elderly patients had similar improvements in clinical symptoms, left ventricular function, and left ventricular reverse remodeling as their counterparts. Similar rates of device-related in-hospital (within 24 hours; P=0.552), early (within 30 days; P=0.984), and long-term adverse events (entire follow-up; hazard ratio, 0.90; P=0.620) were observed between groups. During long-term follow-up (median, 38.6 months; interquartile range, 22.5-61.8 months), all-cause mortality rate was significantly higher among the elderly patients. However, the differences in cumulative event rates started after 4 years of follow-up (P=0.013), and the cause of death was mainly noncardiac (29% in the elderly versus 19% in nonelderly; P<0.001). Diabetes mellitus (hazard ratio, 2.322; P=0.019), impaired renal function (hazard ratio, 0.975; P=0.006), and reduced 6-minute walk distance (hazard ratio, 0.996; P<0.019) were independently associated with all-cause mortality in elderly patients. CONCLUSIONS: CRT efficacy and device-related adverse events in elderly patients were comparable with that of nonelderly patients. However, after 4 years of follow-up, elderly patients showed worse survival and the cause of death was mainly noncardiac. Diabetes mellitus, impaired renal function, and reduced 6-minute walk distance were independently associated with all-cause mortality of elderly patients.

Significant lead-induced tricuspid regurgitation is associated with poor prognosis at long-term follow-up.

BACKGROUND: Although the presence of an RV lead is a potential cause of tricuspid regurgitation (TR), the clinical impact of significant lead-induced TR is unknown. OBJECTIVE: To evaluate the effect of significant lead-induced TR on cardiac performance and long-term outcome after cardioverter-defibrillator (ICD) or pacemaker implantation. METHODS: A retrospective cohort of 239 ICD (n=191) or pacemaker (n=48) recipients (age 60±14 years, 77% male) from a tertiary care university hospital, with an echocardiographic evaluation before and within 1-1.5 years after device implantation were included. Significant lead-induced TR was defined as TR worsening, reaching a grade ≥2 at follow-up echocardiography. During long-term follow-up (median 58, IQR 35-76 months), all-cause mortality and heart failure related events were recorded. RESULTS: Before device implantation, most patients had TR grade 1 or 2 (64.0%) or no TR (33.9%), but after lead placement, significant TR was seen in 91 patients (38%). Changes in cardiac volumes and function at follow-up were similar between patients with and without significant lead-induced TR, except for larger RV diastolic area (17±6mm(2) vs 16±5mm(2), p=0.009), larger right atrial diameter (39±10 mm vs 36±8 mm, p<0.001) and higher pulmonary arterial pressures (41±15 mm Hg vs 33±10 mm Hg, p<0.001) in patients with significant lead-induced TR. Patients with significant lead-induced TR had worse long-term survival (HR=1.687, p=0.040) and/or more heart failure related events (HR=1.641, p=0.019). At multivariate analysis, significant lead-induced TR was independently associated with all-cause mortality (HR=1.749, p=0.047) together with age, LVEF and percentage RV pacing. CONCLUSIONS: Significant lead-induced TR is associated with poor long-term prognosis.

Cost-effectiveness of primary prevention implantable cardioverter defibrillator treatment: data from a large clinical registry.

BACKGROUND: Although randomized trials have shown the beneficial effect on survival of an implantable cardioverter defibrillator (ICD) as primary prevention therapy in selected patients, data concerning the cost-effectiveness in routine clinical practice remain scarce. Accordingly, the purpose of this study was to assess the cost-effectiveness of primary prevention ICD implantation in the real world. METHODS: Patients receiving primary prevention single-chamber or dual-chamber ICD implantation at the Leiden University Medical Center were included in the study. Using a Markov model, lifetime cost, life years (LYs), and gained quality-adjusted life years (QALYs) were estimated for device recipients and control patients. Data on mortality, complication rates, and device longevity were retrieved from our center and entered into the Markov model. To account for model assumptions, one-way deterministic and probabilistic sensitivity analyses were performed. Importantly, calculations for the estimated incremental cost-effectiveness rate (ICER) per QALY gained are based on several numbers of assumptions, and accordingly findings may have over- or underestimated the cost-effectiveness of ICD therapy. RESULTS: Primary prevention ICD implantation adds an estimated mean of 2.07 LYs and 1.73 QALYs. Increased lifetime cost for single-chamber and dual-chamber ICD recipients were estimated at €60,788 and €64,216, respectively. This resulted for single-chamber ICD recipients, in an estimated ICER of €35,154 per QALY gained. In dual-chamber ICD recipients, an estimated ICER of €37,111 per QALY gained was calculated. According to the probabilistic sensitivity analysis, estimated cost per QALY gained are €35,837 (95% confidence interval [CI]: €28,368-€44,460) for single-chamber and €37,756 (95% CI: €29,055-€46,050) for dual-chamber ICDs. CONCLUSIONS: On the basis of data and detailed costs, derived from routine clinical practice, ICD therapy in selected patients with a reduced left ventricular ejection fraction appears to be cost-effective.

Gender-specific differences in clinical outcome of primary prevention implantable cardioverter defibrillator recipients.

OBJECTIVE: To assess differences in clinical outcome of implantable cardioverter-defibrillator (ICD) treatment in men and women. DESIGN: Prospective cohort study. SETTING: University Medical Center. PATIENTS: 1946 primary prevention ICD recipients (1528 (79%) men and 418 (21%) women). Patients with congenital heart disease were excluded for this analysis. MAIN OUTCOME MEASURES: All-cause mortality, ICD therapy (antitachycardia pacing and shock) and ICD shock. RESULTS: During a median follow-up of 3.3 years (25th-75th percentile 1.4-5.4), 387 (25%) men and 76 (18%) women died. The estimated 5-year cumulative incidence for all-cause mortality was 20% (95% CI 18% to 23%) for men and 14% (95% CI 9% to 19%) for women (log rank p<0.01). After adjustment for potential confounding covariates all-cause mortality was lower in women (HR 0.65; 95% CI 0.49 to 0.84; p<0.01). The 5-year cumulative incidence for appropriate therapy in men was 24% (95% CI 21% to 28%) as compared with 20% (95% CI 14% to 26%) in women (log rank p=0.07). After adjustment, a non-significant trend remained (HR 0.82; 95% CI 0.64 to 1.06; p=0.13). CONCLUSIONS: In clinical practice, 21% of primary prevention ICD recipients are women. Women have lower mortality and tend to experience less appropriate ICD therapy as compared with their male peers.

Remote monitoring of patients with implanted devices: data exchange and integration.

BACKGROUND: Remote follow-up of implanted implantable cardioverter defibrillators (ICDs) may offer a solution to the problem of overcrowded outpatient clinics, and may also be effective in detecting clinical events early. Data obtained from remote follow up systems, as developed by all major device companies, are stored in a central database system, operated and owned by the device company. A problem now arises that the patient's clinical information is partly stored in the local electronic health record (EHR) system in the hospital, and partly in the remote monitoring database, which may potentially result in patient safety issues. METHODS: To address the requirement of integrating remote monitoring data in the local EHR, the Integrating the Healthcare Enterprise (IHE) Implantable Device Cardiac Observation (IDCO) profile has been developed. This IHE IDCO profile has been adapted by all major device companies. RESULTS: In our hospital, we have implemented the IHE IDCO profile to import data from the remote databases from two device vendors into the departmental Cardiology Information System (EPD-Vision). Data is exchanged via a HL7/XML communication protocol, as defined in the IHE IDCO profile. CONCLUSIONS: By implementing the IHE IDCO profile, we have been able to integrate the data from the remote monitoring databases in our local EHRs. It can be expected that remote monitoring systems will develop into dedicated monitoring and therapy platforms. Data retrieved from these systems should form an integral part of the electronic patient record as more and more out-patient clinic care will shift to personalized care provided at a distance, in other words at the patient's home.

Suitability for subcutaneous defibrillator implantation: results based on data from routine clinical practice.

OBJECTIVE: To assess the proportion of current implantable cardioverter defibrillator (ICD) recipients who would be suitable for a subcutaneous lead ICD (S-ICD). DESIGN: A retrospective cohort study. SETTING: Tertiary care facility in the Netherlands. PATIENTS: All patients who received a single- or dual-chamber ICD in the Leiden University Medical Center between 2002 and 2011. Patients with a pre-existent indication for cardiac pacing were excluded. MAIN OUTCOME MEASURE: Suitability for an S-ICD defined as not reaching one of the following endpoints during follow-up: (1) an atrial and/or right ventricular pacing indication, (2) successful antitachycardia pacing without a subsequent shock or (3) an upgrade to a CRT-D device. RESULTS: During a median follow-up of 3.4 years (IQR 1.7-5.7 years), 463 patients (34% of the total population of 1345 patients) reached an endpoint. The cumulative incidence of ICD recipients suitable for an initial S-ICD implantation was 55.5% (95% CI 52.0% to 59.0%) after 5 years. Significant predictors for the unsuitability of an S-ICD were: secondary prevention, severe heart failure and prolonged QRS duration. CONCLUSIONS: After 5 years of follow-up, approximately 55% of the patients would have been suitable for an S-ICD implantation. Several baseline clinical characteristics were demonstrated to be useful in the selection of patients suitable for an S-ICD implantation.