Reclassification of aortic stenosis by fusion of echocardiography and computed tomography in low-gradient aortic stenosis.

BACKGROUND: The integration of computed tomography (CT)-derived left ventricular outflow tract area into the echocardiography-derived continuity equation results in the reclassification of a significant proportion of patients with severe aortic stenosis (AS) into moderate AS based on aortic valve area indexed to body surface area determined by fusion imaging (fusion AVAi). The aim of this study was to evaluate AS severity by a fusion imaging technique in patients with low-gradient AS and to compare the clinical impact of reclassified moderate AS versus severe AS. METHODS: We included 359 consecutive patients who underwent transcatheter aortic valve implantation for low-gradient, severe AS at two academic institutions and created a joint database. The primary endpoint was a composite of all-cause mortality and rehospitalisations for heart failure at 1 year. RESULTS: Overall, 35% of the population (n = 126) were reclassified to moderate AS [median fusion AVAi 0.70 (interquartile range, IQR 0.65-0.80) cm2/m2] and severe AS was retained as the classification in 65% [median fusion AVAi 0.49 (IQR 0.43-0.54) cm2/m2]. Lower body mass index, higher logistic EuroSCORE and larger aortic dimensions characterised patients reclassified to moderate AS. Overall, 57% of patients had a left ventricular ejection fraction (LVEF) <50%. Clinical outcome was similar in patients with reclassified moderate or severe AS. Among patients reclassified to moderate AS, non-cardiac mortality was higher in those with LVEF <50% than in those with LVEF ≥50% (log-rank p = 0.029). CONCLUSIONS: The integration of CT and transthoracic echocardiography to obtain fusion AVAi led to the reclassification of one third of patients with low-gradient AS to moderate AS. Reclassification did not affect clinical outcome, although patients reclassified to moderate AS with a LVEF <50% had worse outcomes owing to excess non-cardiac mortality.

Renal function in patients with significant tricuspid regurgitation: pathophysiological mechanisms and prognostic implications.

BACKGROUND: The pathophysiological mechanisms linking tricuspid regurgitation (TR) and chronic kidney disease (CKD) remain unknown. This study aimed to determine which pathophysiological mechanisms related to TR are independently associated with renal dysfunction and to evaluate the impact of renal impairment on long-term prognosis in patients with significant (≥ moderate) secondary TR. METHODS: A total of 1234 individuals (72 [IQR 63-78] years, 50% male) with significant secondary TR were followed up for the occurrence of all-cause mortality and the presence of significant renal impairment (eGFR of <60 mL min-1  1.73 m-2 ) at the time of baseline echocardiography. RESULTS: Multivariable analysis demonstrated that severe right ventricular (RV) dysfunction (TAPSE < 14 mm) was independently associated with the presence of significant renal impairment (OR 1.49, 95% CI 1.11 to 1.99, P = 0.008). Worse renal function was associated with a significant reduction in survival at 1 and 5 years (85% vs. 87% vs. 68% vs. 58% at 1 year, and 72% vs. 64% vs. 39% vs. 19% at 5 years, for stage 1, 2, 3 and 4-5 CKD groups, respectively, P < 0.001). The presence of severe RV dysfunction was associated with reduced overall survival in stage 1-3 CKD groups, but not in stage 4-5 CKD groups. CONCLUSIONS: Of the pathophysiological mechanisms identified by echocardiography that are associated with significant secondary TR, only severe RV dysfunction was independently associated with the presence of significant renal impairment. In addition, worse renal function according to CKD group was associated with a significant reduction in survival.

Myocardial infarction patients referred to the primary care physician after 1­year treatment according to a guideline-based protocol have a good prognosis.

INTRODUCTION: Identifying ST-elevation myocardial infarction (STEMI) patients who can be referred back to the general practitioner (GP) can improve patient-tailored care. However, the long-term prognosis of patients who are returned to the care of their GP is unknown. Therefore, the aim of this study was to assess the long-term prognosis of patients referred back to the GP after treatment in accordance with a 1-year institutional guideline-based protocol. METHODS: All consecutive patients treated between February 2004 up to May 2013 who completed the 1­year institutional MISSION! Myocardial Infarction (MI) follow-up and who were referred to the GP were evaluated. After 1 year of protocolised monitoring, asymptomatic patients with a left ventricular ejection fraction >45% on echocardiography were referred to the GP. Long-term prognosis was assessed with Kaplan-Meier curves and Cox proportional hazards analysis was used to identify independent predictors for 5­year all-cause mortality and major adverse cardiovascular events (MACE). RESULTS: In total, 922 STEMI patients were included in this study. Mean age was 61.6 ± 11.7 years and 74.4% were male. Median follow-up duration after the 1­year MISSION! MI follow-up was 4.55 years (interquartile range [IQR] 2.28-5.00). The event-free survival was 93.2%. After multivariable analysis, age, not using an angiotensin-converting enzyme (ACE) inhibitor/angiotensin-II (AT2) antagonist and impaired left ventricular function remained statistically significant predictors for 5­year all-cause mortality. Kaplan-Meier curves revealed that 80.3% remained event-free for MACE after 5 years. Multivariable predictors for MACE were current smoking and a mitral regurgitation grade ≥2. CONCLUSION: STEMI patients who are referred back to their GP have an excellent prognosis after being treated according to the 1­year institutional MISSION! MI protocol.

Intramyocardial bone marrow cell injection does not lead to functional improvement in patients with chronic ischaemic heart failure without considerable ischaemia.

BACKGROUND: It has been suggested that bone marrow cell injection may have beneficial effects in patients with chronic ischaemic heart disease. However, previous trials have led to discrepant results of cell-based therapy in patients with chronic heart failure. The aim of this study was to evaluate the efficacy of intramyocardial injection of mononuclear bone marrow cells in patients with chronic ischaemic heart failure with limited stress-inducible myocardial ischaemia. METHODS AND RESULTS: This multicentre, randomised, placebo-controlled trial included 39 patients with no-option chronic ischaemic heart failure with a follow-up of 12 months. A total of 19 patients were randomised to autologous intramyocardial bone marrow cell injection (cell group) and 20 patients received a placebo injection (placebo group). The primary endpoint was the group difference in change of left ventricular ejection fraction, as determined by single-photon emission tomography. On follow-up at 3 and 12 months, change of left ventricular ejection fraction in the cell group was comparable with change in the placebo group (P = 0.47 and P = 0.08, respectively). Also secondary endpoints, including left ventricle volumes, myocardial perfusion, functional and clinical parameters did not significantly change in the cell group as compared to placebo. Neither improvement was demonstrated in a subgroup of patients with stress-inducible ischaemia (P = 0.54 at 3­month and P = 0.15 at 12-month follow-up). CONCLUSION: Intramyocardial bone marrow cell injection does not improve cardiac function, nor functional and clinical parameters in patients with severe chronic ischaemic heart failure with limited stress-inducible ischaemia. CLINICAL TRIAL REGISTRATION: NTR2516.

Different value of coronary calcium score to predict obstructive coronary artery disease in patients with and without moderate chronic kidney disease.

PURPOSE: The coronary calcium score (CCS) predicts significant coronary artery disease (CAD) in the general population. While moderate chronic kidney disease (CKD) is associated with high CCS, the use of CCS to predict significant CAD in these patients is unknown. METHODS: A total of 704 patients underwent computed tomography coronary angiography for the assessment of CCS and CAD. Sixty-nine (10 %) patients had moderate CKD, defined by an estimated glomerular filtration rate (eGFR) between 30 and 59 mL/min/1.73m(2), and the remaining patients were considered to be without significant CKD (eGFR ≥ 60 mL/min/1.73m(2)). RESULTS: Patients with moderate CKD were older, had a higher CCS, and a higher prevalence of obstructive CAD than patients without significant CKD. Receiver-operator curve analysis showed that CCS predicted the presence of obstructive CAD in both patients with moderate CKD and those without significant CKD. In patients with moderate CKD, the optimal cut-off value of CCS to diagnose obstructive CAD was 140 (sensitivity 73 % and specificity of 70 %), and is 2.8 fold higher than in patients without significant CKD (cut-off value = 50; sensitivity 75 % and specificity 75 %). CONCLUSION: The present results demonstrate that CCS can predict obstructive CAD in patients with moderate CKD, although the optimal cut-off value is higher than in patients without significant CKD.

Towards optimal use of antithrombotic therapy of people with cancer at the end of life: A research protocol for the development and implementation of the SERENITY shared decision support tool.

BACKGROUND: Even though antithrombotic therapy has probably little or even negative effects on the well-being of people with cancer during their last year of life, deprescribing antithrombotic therapy at the end of life is rare in practice. It is often continued until death, possibly resulting in excess bleeding, an increased disease burden and higher healthcare costs. METHODS: The SERENITY consortium comprises researchers and clinicians from eight European countries with specialties in different clinical fields, epidemiology and psychology. SERENITY will use a comprehensive approach combining a realist review, flash mob research, epidemiological studies, and qualitative interviews. The results of these studies will be used in a Delphi process to reach a consensus on the optimal design of the shared decision support tool. Next, the shared decision support tool will be tested in a randomised controlled trial. A targeted implementation and dissemination plan will be developed to enable the use of the SERENITY tool across Europe, as well as its incorporation in clinical guidelines and policies. The entire project is funded by Horizon Europe. RESULTS: SERENITY will develop an information-driven shared decision support tool that will facilitate treatment decisions regarding the appropriate use of antithrombotic therapy in people with cancer at the end of life. CONCLUSIONS: We aim to develop an intervention that guides the appropriate use of antithrombotic therapy, prevents bleeding complications, and saves healthcare costs. Hopefully, usage of the tool leads to enhanced empowerment and improved quality of life and treatment satisfaction of people with advanced cancer and their care givers.

Reprinted article "A combination of statins and beta-blockers is independently associated with a reduction in the incidence of perioperative mortality and nonfatal myocardial infarction in patients undergoing abdominal aortic aneurysm surgery".

OBJECTIVE: To investigate the combined beneficial effect of statin and beta-blocker use on perioperative mortality and myocardial infarction (MI) in patients undergoing abdominal aortic aneurysm surgery (AAA). BACKGROUND: Patients undergoing elective AAA-surgery identified by clinical risk factors and dobutamine stress echocardiography (DSE) as being at high-risk often have considerable cardiac complication rate despite the use of beta-blockers. METHODS: We studied 570 patients (mean age 69 ±9 years, 486 males) who underwent AAA-surgery between 1991 and 2001 at the Erasmus MC. Patients were evaluated for clinical risk factors (age>70 years, histories of MI, angina, diabetes mellitus, stroke, renal failure, heart failure and pulmonary disease), DSE, statin and beta-blocker use. The main outcome was a composite of perioperative mortality and MI within 30 days of surgery. RESULTS: Perioperative mortality or MI occurred in 51 (8.9%) patients. The incidence of the composite endpoint was significantly lower in statin users compared to nonusers (3.7% vs. 11.0%; crude odds ratio (OR): 0.31, 95% confidence interval (CI): 0.13-0.74; p = 0.01). After correcting for other covariates, the association between statin use and reduced incidence of the composite endpoint remained unchanged (OR: 0.24,95% CI: 0.10-0.70; p = 0.01). Beta-blocker use was also associated with a significant reduction in the composite endpoint (OR: 0.24, 95% CI: 0.11-0.54). Patients using a combination of statins and beta-blockers appeared to be at lower risk for the composite endpoint across multiple cardiac risk strata; particularly patients with 3 or more risk factors experienced significantly lower perioperative events. CONCLUSIONS: A combination of statin and beta-blocker use in patients with AAA-surgery is associated with a reduced incidence of perioperative mortality and nonfatal MI particularly in patients at the highest risk.

Asymptomatic low ankle-brachial index in vascular surgery patients: a predictor of perioperative myocardial damage.

OBJECTIVES: This study evaluated the prognostic value of asymptomatic low ankle-brachial index (ABI) to predict perioperative myocardial damage, incremental to conventional cardiac risk factors imbedded in cardiac risk indices (Revised Cardiac index and Adapted Lee index). MATERIALS AND METHODS: Preoperative ABI measurements were performed in 627 consecutive vascular surgery patients (carotid artery or abdominal aortic aneurysm repair). An ABI<0.90 was considered abnormal. Patients with ABI>1.40 or (a history of) intermittent claudication were excluded. Serial troponin-T measurements were performed routinely before and after surgery. The main study endpoint was perioperative myocardial damage, the composite of myocardial ischaemia and infarction. Multivariate regression analyses, adjusted for conventional risk factors, evaluated the relation between asymptomatic low ABI and perioperative myocardial damage. RESULTS: In total, 148 (23%) patients had asymptomatic low ABI (mean 0.73, standard deviation+/-0.13). Perioperative myocardial damage was recorded in 107 (18%) patients. Multivariate regression analyses demonstrated that asymptomatic low ABI was associated with an increased risk of perioperative myocardial damage (odds ratio (OR): 2.4, 95% CI: 1.4-4.2) CONCLUSIONS: This study demonstrated that asymptomatic low ABI has a prognostic value to predict perioperative myocardial damage in vascular surgery patients, incremental to risk factors imbedded in conventional cardiac risk indices.

Prognosis of vascular surgery patients using a quantitative assessment of troponin T release: is the crystal ball still clear?

BACKGROUND: Cardiac troponin T (cTnT) assays with increased sensitivity might increase the number of positive tests. Using the area under the curve (AUC) with serial sampling of cTnT an exact quantification of the myocardial damage size can be made. We compared the prognosis of vascular surgery patients with integrated cTnT-AUC values to continuous and standard 12-lead electrocardiography (ECG) changes. METHODS: 513 Patients were monitored. cTnT sampling was performed on postoperative days 1, 3, 7, 30 and/or at discharge or whenever clinically indicated. If cTnT release occurred, daily measurements of cTnT were performed, until baseline was achieved. CTnT-AUC was quantified and divided in tertiles. All-cause mortality and cardiovascular events (cardiac death and myocardial infarction) were noted during follow-up. RESULTS: 81/513 (16%) Patients had cTnT release. After adjustment for gender, cardiac risk factors, and site and type of surgery, those in the highest cTnT-AUC tertile were associated with a significantly worse cardiovascular outcome and long-term mortality (HR 20.2; 95% CI 10.2-40.0 and HR 4.0; 95% CI 2.0-7.8 respectively). Receiver operator analysis showed that the best cut-off value for cTnT-AUC was <0.01 days*ng m for predicting long-term cardiovascular events and all-cause mortality. CONCLUSION: In vascular surgery patients quantitative assessment of cTnT strongly predicts long-term outcome.

Process of care partly explains the variation in mortality between hospitals after peripheral vascular surgery.

OBJECTIVES: The aim of this study is to investigate whether variation in mortality at hospital level reflects differences in quality of care of peripheral vascular surgery patients. DESIGN: Observational study. MATERIALS: In 11 hospitals in the Netherlands, 711 consecutive vascular surgery patients were enrolled. METHODS: Multilevel logistic regression models were used to relate patient characteristics, structure and process of care to mortality at 1 year. The models were constructed by consecutively adding age, sex and Lee index, then remaining risk factors, followed by structural measures for quality of care and finally, selected process of care parameters. RESULTS: Total 1-year mortality was 11%, ranging from 6% to 26% in different hospitals. Large differences in patient characteristics and quality indicators were observed between hospitals (e.g., age>70 years: 28-58%; beta-blocker therapy: 39-87%). Adjusted analyses showed that a large part of variation in mortality was explained by age, sex and the Lee index (Akaike's information criterion (AIC)=59, p<0.001). Another substantial part of the variation was explained by process of care (AIC=5, p=0.001). CONCLUSIONS: Differences between hospitals exist in patient characteristics, structure of care, process of care and mortality. Even after adjusting for the patient population at risk, a substantial part of the variation in mortality can be explained by differences in process measures of quality of care.

Prognosis of atrial fibrillation in patients with symptomatic peripheral arterial disease: data from the REduction of Atherothrombosis for Continued Health (REACH) Registry.

BACKGROUND: Atrial fibrillation (AF) is a significant risk factor for cardiovascular (CV) mortality. This study aims to evaluate the prognostic implication of AF in patients with peripheral arterial disease (PAD). METHODS: The International Reduction of Atherothrombosis for Continued Health (REACH) Registry included 23,542 outpatients in Europe with established coronary artery disease, cerebrovascular disease (CVD), PAD and/or > or =3 risk factors. Of these, 3753 patients had symptomatic PAD. CV risk factors were determined at baseline. Study end point was a combination of cardiac death, non-fatal myocardial infarction (MI) and stroke (CV events) during 2 years of follow-up. Cox regression analysis adjusted for age, gender and other risk factors (i.e., congestive heart failure, coronary artery re-vascularisation, coronary artery bypass grafting (CABG), MI, hypertension, stroke, current smoking and diabetes) was used. RESULTS: Of 3753 PAD patients, 392 (10%) were known to have AF. Patients with AF were older and had a higher prevalence of CVD, diabetes and hypertension. Long-term CV mortality occurred in 5.6% of patients with AF and in 1.6% of those without AF (p<0.001). Multivariable analyses showed that AF was an independent predictor of late CV events (hazard ratio (HR): 1.5; 95% confidence interval (CI): 1.09-2.0). CONCLUSION: AF is common in European patients with symptomatic PAD and is independently associated with a worse 2-year CV outcome.

Relation between regional and global systolic function in patients with ischemic cardiomyopathy after beta-blocker therapy or revascularization.

BACKGROUND: To assess the relationship between improved regional and global myocardial function in patients with ischemic cardiomyopathy in response to beta-blocker therapy or revascularization. MATERIALS AND METHODS: Cardiovascular magnetic resonance (CMR) was performed in 32 patients with ischemic cardiomyopathy before and 8 +/- 2 months after therapy. Patients were assigned clinically to beta-blocker therapy (n = 20) or revascularization (n = 12). CMR at baseline was performed to assess regional and global LV function at rest and under low-dose dobutamine. Wall thickening was analyzed in dysfunctional, adjacent, and remote segments. Follow-up CMR included rest function evaluation. RESULTS: Augmentation of wall thickening during dobutamine at baseline was similar in dysfunctional, adjacent and remote segments in both patient groups. Therefore, baseline characteristics were similar for both patient groups. In both patient groups resting LV ejection fraction and end-systolic volume improved significantly (p < 0.05) at follow-up. Stepwise multivariate analysis revealed that improvement in global LV ejection fraction in the beta-blocker treated patients was significantly related to improved function of remote myocardium (p < 0.05), whereas in the revascularized patients improved function in dysfunctional and adjacent segments was more pronounced (p < 0.05). CONCLUSION: In patients with chronic ischemic LV dysfunction, beta-Blocker therapy or revascularization resulted in a similar improvement of global systolic LV function. However, after beta-blocker therapy, improved global systolic function was mainly related to improved contraction of remote myocardium, whereas after revascularization the dysfunctional and adjacent regions contributed predominantly to the improved global systolic function.

Echocardiography and non-invasive imaging in cardiac resynchronization therapy.

The beneficial effects of cardiac resynchronization therapy (CRT) on morbidity and mortality in advanced heart failure patients have been extensively demonstrated. However, previous single- and multicenter studies demonstrated that approximately 30-40% of CRT patients do not show significant clinical improvement or LV reverse remodeling despite fulfilling current inclusion criteria. In search of novel indices that may help to improve the selection of responders to CRT, non-invasive multimodality imaging has provided further insight into the mechanisms underlying CRT response. LV dyssynchrony, extent and location of myocardial scar and LV lead position have shown to be independent determinants of CRT response. An integrated evaluation of these three pathophysiological mechanisms may provide a more accurate selection of heart failure patients who will benefit from CRT and may maximize the cost-effectiveness of this therapy. The present review article provides a critical appraisal of the role of multimodality imaging in the selection of heart failure patients who are candidates for CRT with special focus on the assessment of LV mechanical dyssynchrony, LV myocardial scar tissue extent and LV lead position.

Clinical application of CT coronary angiography: state of the art.

In recent years, multi-slice computed tomography (MSCT) technology has developed rapidly, allowing high-resolution non-invasive imaging of the coronary arteries and surrounding structures. Since the introduction of MSCT, acquisition time, detector number, spatial and temporal resolution have continuously improved with each new scanner generation, resulting in excellent image quality and diagnostic accuracy in the detection of coronary artery disease (CAD). At the same time, developments in MSCT technology have focused on reduction of the radiation dose. In particular, the availability of dose modulation and prospective ECG gating have drastically reduced patient radiation dose. Moreover, with the introduction of 320-slice MSCT, volumetric scanning of the entire heart has become possible in a single heart beat or gantry rotation, thereby eliminating oversampling and stair-step artifact. The present article provides an overview of state of the art clinical applications of cardiac MSCT, including the diagnosis of CAD, evaluation of plaque morphology and composition, prognostification, and the evaluation of left ventricular function and aortic and mitral valve anatomy.

The effect of statins on perioperative events in patients undergoing vascular surgery.

Despite recent advancements in perioperative care and guideline recommendations, patients undergoing vascular surgery remain at risk for perioperative cardiovascular complications. In this review, the results are summarized of the most recent studies on the effectiveness and safety of perioperative statin use for the prevention of these perioperative cardiovascular complications. Perioperative statin therapy was associated with an improvement in postoperative cardiovascular outcome and a reduction in serum lipid levels and levels of inflammation markers.

COPD and cancer mortality: the influence of statins.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with an increased risk of lung cancer, independently of smoking. However, the relationship between COPD and total cancer mortality is less certain. A study was undertaken to investigate the association between COPD and total cancer mortality and to determine whether the use of statins, which have been associated with cancer risk in other settings, modified this relationship. METHODS: The study included 3371 patients with peripheral arterial disease who underwent vascular surgery between 1990 and 2006; 1310 (39%) had COPD and the rest did not. The primary end point was cancer mortality (lung and extrapulmonary) over a median follow-up of 5 years. RESULTS: COPD was associated with an increased risk of both lung cancer mortality (hazard ratio (HR) 2.06; 95% CI 1.32 to 3.20) and extrapulmonary cancer mortality (HR 1.43; 95% CI 1.06 to 1.94). The excess risk was mostly driven by patients with moderate and severe COPD. There was a trend towards a lower risk of cancer mortality among patients with COPD who used statins compared with patients with COPD who did not use statins (HR 0.57; 95% CI 0.32 to 1.01). Interestingly, the risk of extrapulmonary cancer mortality was lower among statin users with COPD (HR 0.49; 95% CI 0.24 to 0.99). CONCLUSIONS: COPD was associated with increased lung and extrapulmonary cancer mortality in this large cohort of patients with peripheral arterial disease undergoing vascular surgery. The risk of lung cancer mortality increased with progression of COPD. Statins were associated with a reduced risk of extrapulmonary cancer mortality in patients with COPD.

Short-term overt hypothyroidism induces discrete diastolic dysfunction in patients treated for differentiated thyroid carcinoma.

BACKGROUND: Thyroid hormone has important effects on the cardiovascular system. The consequences of episodes of acute hypothyroidism on cardiac function have been investigated in only a few studies, and their results are inconclusive. Our objective was to investigate the effects of acute hypothyroidism on cardiac function in patients with iatrogenically induced subclinical hyperthyroidism after treatment for differentiated thyroid carcinoma. MATERIAL AND METHODS: Fourteen patients with a history of differentiated thyroid carcinoma on thyroid-stimulating hormone (TSH)-suppressive thyroxine replacement therapy were studied. We assessed cardiac function before, and 1 and 4 weeks after withdrawal of thyroxine substitution. We measured serum levels of free thyroxine, triiodothyronine and TSH and used a new sophisticated Doppler echocardiography technique, tissue Doppler imaging (TDI), to assess detailed and quantitative assessment of systolic and diastolic cardiac function. Echocardiographic parameters in patients were compared to controls. RESULTS: Compared to controls, patients had higher left ventricular mass and wall thickness and decreased diastolic function during TSH-suppressive l-thyroxine substitution therapy. Thyroxine withdrawal resulted in a decrease in both early (E) and late (A) diastolic mitral inflow velocities, without impact on E/A ratio. Using TDI, late diastolic velocity (A') decreased without impact on E'/A' ratio. Left ventricular dimensions, wall thickness and mass did not change during thyroxine withdrawal. CONCLUSIONS: Subclinical hyperthyroidism is accompanied by diastolic dysfunction. Subsequent acute hypothyroidism induces only subtle changes in diastolic function.