M. J. Cramer

Refining success of cardiac resynchronization therapy using a simple score predicting the amount of reverse ventricular remodelling : results from the Markers and Response to CRT (MARC) study

AimsnCardiac resynchronization therapy (CRT) reduces morbidity and mortality in systolic heart failure patients with ventricular conduction delay. Variability of individual response to CRT warrants improved patient selection. The Markers and Response to CRT (MARC) study was designed to investigate markers related to response to CRT.nnnMethods and resultsnWe prospectively studied the ability of 11 clinical, 11 electrocardiographic, 4 echocardiographic, and 16 blood biomarkers to predict CRT response in 240 patients. Response was measured by the reduction of indexed left ventricular end-systolic volume (LVESVi) at 6 months follow-up. Biomarkers were related to LVESVi change using log-linear regression on continuous scale. Covariates that were significant univariately were included in a multivariable model. The final model was utilized to compose a response score. Age was 67 ± 10 years, 63% were male, 46% had ischaemic aetiology, LV ejection fraction was 26 ± 8%, LVESVi was 75 ± 31u2009mL/m2, and QRS was 178 ± 23u2009ms. At 6 months LVESVi was reduced to 58 ± 31u2009mL/m2 (relative reduction of 22 ± 24%), 130 patients (61%) showed ≥ 15% LVESVi reduction. In univariate analysis 17 parameters were significantly associated with LVESVi change. In the final model age, QRSAREA (using vectorcardiography) and two echocardiographic markers (interventricular mechanical delay and apical rocking) remained significantly associated with the amount of reverse ventricular remodelling. This CAVIAR (CRT-Age-Vectorcardiographic QRSAREA -Interventricular Mechanical delay-Apical Rocking) response score also predicted clinical outcome assessed by heart failure hospitalizations and all-cause mortality.nnnConclusionsnThe CAVIAR response score predicts the amount of reverse remodelling after CRT and may be used to improve patient selection. Clinical Trials: NCT01519908.

99Tcm-SESTAMIBI for planar myocardial perfusion imaging; not as ideal as the physical properties

99Tcm-methoxyisobutyl isonitrile (Tc-SESTAMIBI) has recently been introduced as a new myocardial perfusion agent which exhibits ideal physical properties for imaging with the gamma camera. To assess the diagnostic accuracy of planar Tc-SESTAMIBI, myocardial perfusion imaging was performed in 60 consecutive patients at rest and during exercise. The results were compared with coronary angiographie findings, obtained within 3 months of the exercise test. Planar 201Tl images were also performed on the same day and to the same level of stress as the Tc-SESTAMIBI exercise. Exact segmentai agreement between Tc-SESTAMIBI and 201Tl was 77%. Nineteen per cent of all 900 segments demonstrated ischaemia with Tc-SESTAMIBI and 20% with 201Tl.The overall sensitivity for detecting haemodynamically significant coronary artery disease with Tc-SESTAMIBI was 86% and specificity was 78%; with 201Tl the values were 89 and 78%, respectively (differences not significant). Vessel-specific comparative detection rates revealed no statistical significant differences between both radiopharmaceuticals. Intra-observer variability for Tc-SESTAMIBI images was 12% and for 201Tl it was 14%. Inter-observer variability for Tc-SESTAMIBI was 14% and for 2O1T117%.Although the physical characteristics of Tc-SESTAMIBI allow crisp and clear high-count density imaging, no significant differences are found when planar images are compared with 201Tl and are well within observer variabilities.

Echocardiography and cardiac resynchronisation therapy, friends or foes?

Echocardiography is used in cardiac resynchronisation therapy (CRT) to assess cardiac function, and in particular left ventricular (LV) volumetric status, and prediction of response. Despite its widespread applicability, LV volumes determined by echocardiography have inherent measurement errors, interobserver and intraobserver variability, and discrepancies with the gold standard magnetic resonance imaging. Echocardiographic predictors of CRT response are based on mechanical dyssynchrony. However, parameters are mainly tested in single-centre studies or lack feasibility. Speckle tracking echocardiography can guide LV lead placement, improving volumetric response and clinical outcome by guiding lead positioning towards the latest contracting segment. Results on optimisation of CRT device settings using echocardiographic indices have so far been rather disappointing, as results suffer from noise. Defining response by echocardiography seems valid, although re-assessment after 6 months is advisable, as patients can show both continuous improvement as well as deterioration after the initial response. Three-dimensional echocardiography is interesting for future implications, as it can determine volume, dyssynchrony and viability in a single recording, although image quality needs to be adequate. Deformation patterns from the septum and the derived parameters are promising, although validation in a multicentre trial is required. We conclude that echocardiography has a pivotal role in CRT, although clinicians should know its shortcomings.

Long-term cardiovascular health in adult cancer survivors

The number of cancer survivors has tremendously increased over the past decades as a result of aging of the population and improvements in early cancer detection and treatment. Ongoing successes in cancer treatment are expected to result in a further increase in the number of long-term survivors. However, cancer treatment can have detrimental cardiovascular side-effects that impact morbidity and mortality, reducing quality of life in cancer survivors. The spectrum of radiotherapy- and chemotherapy-induced cardiovascular disease is broad, varying from subclinical valvular dysfunction to overt congestive heart failure, and such effects may not be apparent for more than twenty years after the initial cancer treatment. Awareness of these long-term side-effects is of crucial value in the management of these patients, in order to reduce the impact of cardiovascular morbidity and mortality. This review provides a comprehensive overview of the long-term cardiovascular complications of cancer treatments (radiotherapy and chemotherapy) in adult cancer survivors.

How I do it: feasibility of a new ultrasound probe fixator to facilitate high quality stress echocardiography

BackgroundStress echocardiography (SE) has recently regained momentum as an important diagnostic tool for the assessment of both ischemic and non-ischemic heart disease. Performing SE during physical exercise is challenging due to a suboptimal patient position and vigorous movements of the patient’s chest. This hampers a stable ultrasound position and reduces the diagnostic performance of SE. A stable ultrasound probe position would facilitate producing high quality images during continuous measurements. With Probefix (Usono, Eindhoven, The Netherlands), a newly developed tool to fixate the ultrasound probe to the patient’s chest, stabilization of the probe during physical exercise is possible.Implementation and resultsThe technique of SE with the Probefix and its’ feasibility are evaluated in a small pilot study. Probefix fixates the ultrasound probe to the patient’s chest, using two chest straps and a fixation device. The ultrasound probe position and angle may be altered with a relative high degree of freedom. We tested the Probefix for continuous echocardiographic imaging in 12 study subjects during supine and upright ergometer stress tests. One patient was unable to perform exercise and in two study subjects good quality images were not achieved. In the other patients (82%) a stable probe position was obtained, with subsequent good quality echocardiographic images during SE.ConclusionWe have demonstrated the feasibility of the Probefix support during ergometer tests in supine and upright positions and conclude that this external fixator may facilitate continuous monitoring of cardiac function in a group of patients.

Quantitative thallium-201 myocardial exercise scintigraphy in normal subjects and patients with normal coronary arteries

Quantitative thallium-201 myocardial exercise scintigraphy was tested in two patient populations representing alternative standards for cardiac normality: group I comprised 18 male uncatheterized patients with a low likelihood of coronary artery disease (CAD); group II contained 41 patients with normal coronary arteriograms. Group I patients were younger, they achieved a higher rate-pressure product than group II patients; all had normal findings by physical examination and electrocardiography at rest and exercise. Group II patients comprised 21 females, 11 patients showed abnormal electrocardiography at rest, and five patients showed ischemic ST depression during exercise. Twelve patients had signs of minimal CAD. Twelve patients revealed abnormal visual and quantitative thallium findings, three of these patients had minimal CAD. Profiles of uptake and washout of thallium-201 were derived from both patient groups, and compared with normal limits developed by Maddahi et al. Furthermore, low likelihood and angiographically normal patients may differ substantially, and both sets of normal patients should be considered when establishing criteria for abnormality in exercise thallium imaging. When commercial software containing normal limits for quantitative analysis of exercise thallium-201 imaging is used in clinical practice, it is mandatory to compare these with normal limits of uptake and washout of thallium-201, derived from the less heterogeneous group of low-likelihood subjects, which should be used in selecting a normal population to define normality.

Cardio-oncology: an overview on outpatient management and future developments

Recent advances in the early detection and treatment of cancer have led to increasing numbers of cancer survivors worldwide. Nonetheless, despite major improvements in the outcome of these patients, long-term side effects of radio- and chemotherapy affect both patient survival and quality of life, independent of the oncological prognosis. Chemotherapy-related cardiac dysfunction is one of the most notorious short-term side effects of anticancer treatment, occurring in ~10% of patients. Progression to overt heart failure carries axa0strikingly poor prognosis with axa02-year mortality rate of 60%. Early detection of left ventricular damage by periodic monitoring and prompt initiation of heart failure treatment is key in improving cardiovascular prognosis. To meet the growing demand for axa0specialised interdisciplinary approach for the prevention and management of cardiovascular complications induced by cancer treatment, axa0new discipline termed cardio-oncology has evolved. However, anxa0uniform, multidisciplinary approach is currently lacking in the Netherlands. This overview provides an introduction and comprehensive summary of this emerging discipline and offers axa0practical strategy for the outpatient management of this specific patient population.

Strain imaging to predict response to cardiac resynchronization therapy: a systematic comparison of strain parameters using multiple imaging techniques: Strain imaging techniques in cardiac resynchronization therapy

Various strain parameters and multiple imaging techniques are presently available including cardiovascular magnetic resonance (CMR) tagging (CMR‐TAG), CMR feature tracking (CMR‐FT), and speckle tracking echocardiography (STE). This study aims to compare predictive performance of different strain parameters and evaluate results per imaging technique to predict cardiac resynchronization therapy (CRT) response.

Chemotherapy-Related Cardiac Dysfunction: A Systematic Review of Genetic Variants Modulating Individual Risk

Chemotherapy-related cardiac dysfunction is a significant side effect of anticancer treatment. Risk stratification is based on clinical- and treatment-related risk factors that do not adequately explain individual susceptibility. The addition of genetic variants may improve risk assessment. We conducted a systematic literature search in PubMed and Embase, to identify studies investigating genetic risk factors for chemotherapy-related cardiac dysfunction. Included were articles describing genetic variants in humans altering susceptibility to chemotherapy-related cardiac dysfunction. The validity of identified studies was assessed by 10 criteria, including assessment of population stratification, statistical methodology, and replication of findings. We identified 40 studies: 34 exploring genetic risk factors for anthracycline-induced cardiotoxicity (n=9678) and 6 studies related to trastuzumab-associated cardiotoxicity (n=642). The majority (35/40) of studies had a candidate gene approach, whereas 5 genome-wide association studies have been performed. We identified 25 genetic variants in 20 genes and 2 intergenic variants reported significant at least once. The overall validity of studies was limited, with small cohorts, failure to assess population ancestry and lack of replication. SNPs with the most robust evidence up to this point are CELF4 rs1786814 (sarcomere structure and function), RARG rs2229774 (topoisomerase-2&bgr; expression), SLC28A3 rs7853758 (drug transport), UGT1A6 rs17863783 (drug metabolism), and 1 intergenic variant (rs28714259). Existing evidence supports the hypothesis that genetic variation contributes to chemotherapy-related cardiac dysfunction. Although many variants identified by this systematic review show potential to improve risk stratification, future studies are necessary for validation and assessment of their value in a diagnostic and prognostic setting.

Erratum to: Echocardiography and cardiac resynchronization therapy, friends or foes?

Erratum to: Neth Heart J (2016) 24:25–38 n nDOI 10.1007/s12471-015-0769-3 n nFigures u200bFigures33 and u200band44 and the captions of figures u200bfigures2,2, u200b,3,3, and u200band44 in the original article were incorrect and should have appeared as presented in this erratum. The editors apologise for this oversight and any confusion this may have caused. n n n nFig. 2 n nSchematic representation of apical rocking and septal flash. Schematic representation of the left ventricle in echocardiographic AP4CH view, showing both septal flash and apical rocking due to LBBB induced mechanical dyssynchrony. a early septal contraction ... n n n n n nFig. 3 n nExample of echocardiographic data obtained from a responder to CRT. Apical four chamber view, colour Doppler, septal strain and pulsed-wave Doppler acquisition of a responder to CRT, before, and 6 and 12 months after implantation. Note the continuous ... n n n n n nFig. 4 n nRadial strain analysis of parasternal short axis images. Parasternal short axis (PSAX) views and radial strain analysis of a patient with LBBB, imaged prior to CRT implantation. LV lead placement resulted in a mid-posterolateral position (green curve ...