Cardiac [99mTc]Tc-hydroxydiphosphonate uptake on bone scintigraphy in patients with hereditary transthyretin amyloidosis: an early follow-up marker?

PURPOSE: There is a need for early quantitative markers of potential treatment response in patients with hereditary transthyretin (ATTRv) amyloidosis to guide therapy. This study aims to evaluate changes in cardiac tracer uptake on bone scintigraphy in ATTRv amyloidosis patients on different treatments. METHODS: In this retrospective cohort study, outcomes of 20 patients treated with the transthyretin (TTR) gene silencer patisiran were compared to 12 patients treated with a TTR-stabilizer. Changes in NYHA class, cardiac biomarkers in serum, wall thickness, and diastolic parameters on echocardiography and NYHA class during treatment were evaluated. RESULTS: Median heart/whole-body (H/WB) ratio on bone scintigraphy decreased from 4.84 [4.00 to 5.31] to 4.16 [3.66 to 4.81] (p < .001) in patients treated with patisiran for 29 [15-34] months. No changes in the other follow-up parameters were observed. In patients treated with a TTR-stabilizer for 24 [20 to 30] months, H/WB ratio increased from 4.46 [3.24 to 5.13] to 4.96 [ 3.39 to 5.80] (p = .010), and troponin T increased from 19.5 [9.3 to 34.0] ng/L to 20.0 [11.8 to 47.8] ng/L (p = .025). All other parameters did not change during treatment with a TTR-stabilizer. CONCLUSION: A change in cardiac tracer uptake on bone scintigraphy may be an early marker of treatment-specific response or disease progression in ATTRv amyloidosis patients.

Left ventricular strain-volume loops and diastolic dysfunction in suspected heart failure with preserved ejection fraction.

BACKGROUND: Presence of left ventricular diastolic dysfunction (DD) is key in the pathogenesis of heart failure with preserved ejection fraction (HFpEF). However, non-invasive assessment of diastolic function is complex, cumbersome, and largely based on consensus recommendations. Novel imaging techniques may help detecting DD. Therefore, we compared left ventricular strain-volume loop (SVL) characteristics and diastolic (dys-)function in suspected HFpEF patients. METHOD AND RESULTS: 257 suspected HFpEF patients with sinus rhythm during echocardiography were prospectively included. 211 patients with quality-controlled images and strain and volume analysis were classified according to the 2016 ASE/EACVI recommendations. Patients with indeterminate diastolic function were excluded, resulting in two groups: normal diastolic function (control; n = 65) and DD (n = 91). Patients with DD were older (74.8 ± 6.9 vs. 68.5 ± 9.4 years, p < 0.001), more often female (88% vs 72%, p = 0.021), and more often had a history of atrial fibrillation (42% vs. 23%, p = 0.024) and hypertension (91% vs. 71%, p = 0.001) compared to normal diastolic function. SVL analysis showed a larger uncoupling i.e., a different longitudinal strain contribution to volume change, in DD compared to controls (0.556 ± 1.10% vs. -0.051 ± 1.14%, respectively, P < 0.001). This observation suggests different deformational properties during the cardiac cycle. After adjustment for age, sex, history of atrial fibrillation and hypertension, we found an adjusted odds ratio of 1.68 (95% confidence interval 1.19-2.47) for DD per unit increase in uncoupling (range: -2.95-3.20). CONCLUSION: Uncoupling of the SVL is independently associated with DD. This might provide novel insights in cardiac mechanics and new opportunities to assess diastolic function non-invasively.

Introduction of a new scoring tool to identify clinically stable heart failure patients.

INTRODUCTION: Heart failure (HF) poses a burden on specialist care, making referral of clinically stable HF patients to primary care a desirable goal. However, a structured approach to guide patient referral is lacking. METHODS: The Maastricht Instability Score-Heart Failure (MIS-HF) questionnaire was developed to objectively stratify the clinical status of HF patients: patients with a low MIS-HF (0-2 points, indicating a stable clinical condition) were considered for treatment in primary care, whereas high scores (> 2 points) indicated the need for specialised care. The MIS-HF was evaluated in 637 consecutive HF patients presenting between 2015 and 2018 at Maastricht University Medical Centre. RESULTS: Of the 637 patients, 329 (52%) had a low score and 205 of these 329 (62%) patients were referred to primary care. The remaining 124 (38%) patients remained in secondary care. Of the 308 (48%) patients with a high score (> 2 points), 265 (86%) remained in secondary care and 41 (14%) were referred to primary care. The primary composite endpoint (mortality, cardiac hospital admissions) occurred more frequently in patients with a high compared to those with a low MIS-HF after 1 year of follow-up (29.2% vs 10.9%; odds ratio (OR) 3.36, 95% confidence interval (CI) 2.20-5.14). No significant difference in the composite endpoint (9.8% vs 12.9%; OR 0.73, 95% CI 0.36-1.47) was found between patients with a low MIS-HF treated in primary versus secondary care. CONCLUSION: The MIS-HF questionnaire may improve referral policies, as it helps to identify HF patients that can safely be referred to primary care.

Effects of tailored telemonitoring on functional status and health-related quality of life in patients with heart failure.

BACKGROUND: Functional status and health-related quality of life (HRQoL) are important in patients with heart failure (HF). Little is known about the effect of telemonitoring on functional status and HRQoL in that population. METHODS AND RESULTS: A total of 382 patients with HF (New York Heart Association class 2-4) were included in a randomised controlled trial to investigate the effect of tailored telemonitoring on improving HRQoL and functional status in HF patients. Randomisation was computer-generated with stratification per centre. At baseline and after 12 months, patients' functional status was determined by metabolic equivalent scores (METS). HRQoL was measured with the EuroQol five dimensions questionnaire (EQ-5D), visual analogue scale (VAS) and Borg rating of perceived exertion scale (Borg). Additional outcome data included number of HF-related outpatient clinic visits and mortality. Telemonitoring was statistically significantly related to an increase in METS after 1 year (regression coefficient 0.318; p = 0.01). Telemonitoring did not improve Borg, EQ-5D or VAS scores after 1 year. EQ-5D [hazard ratio (HR) 0.20, 95% confidence interval (CI) 0.07-0.54], VAS (HR 0.98, 95% CI 0.96-0.99), Borg (HR 1.21, 95% CI 1.11-1.31) and METS (HR 0.73, 95% CI 0.58-0.93) at baseline were significantly associated with survival after 12 months. CONCLUSIONS: Tailored telemonitoring stabilised the functional status of HF patients but did not improve HRQoL. Therefore, telemonitoring may help to prevent deterioration of exercise capacity in patients with HF. However, because our study is a reanalysis of a randomised controlled trial (RCT), this is considered hypothesis-generating and should be confirmed by adequately powered RCTs.

Impact of airflow limitation in chronic heart failure.

BACKGROUND: Comorbidities are common in chronic heart failure (HF) patients, but diagnoses are often not based on objective testing. Chronic obstructive pulmonary disease (COPD) is an important comorbidity and often neglected because of shared symptoms and risk factors. Precise prevalence and consequences are not well known. Therefore, we investigated prevalence, pulmonary treatment, symptoms and quality of life (QOL) of COPD in patients with chronic HF. METHODS: 205 patients with stable HF for at least 1 month, aged above 50 years, were included from our outpatient cardiology clinic, irrespective of left ventricular ejection fraction. Patients performed post-bronchodilator spirometry, a six-minute walk test (6-MWT) and completed the Kansas City Cardiomyopathy Questionnaire (KCCQ). COPD was diagnosed according to GOLD criteria. Restrictive lung function was defined as FEV1/FVC ≥0.70 and FVC <80% of predicted value. The BODE and ADO index, risk scores in COPD patients, were calculated. RESULTS: Almost 40% fulfilled the criteria of COPD and 7% had restrictive lung disease, the latter being excluded from further analysis. Noteworthy, 63% of the COPD patients were undiagnosed and 8% of those without COPD used inhalation therapy. Patients with COPD had more shortness of breath despite little difference in HF severity and similar other comorbidities. KCCQ was significantly worse in COPD patients. The ADO and BODE indices were significantly different. CONCLUSION: COPD is very common in unselected HF patients. It was often not diagnosed and many patients received treatment without being diagnosed with COPD. Presence of COPD worsens symptoms and negatively effects cardiac specific QOL.

Analysis of right and left ventricular deformation in former world class swimmers: evaluation using speckle tracking.

AIM: There is a longstanding debate over the long-term effect of intensive endurance training on cardiac function. Usually, echocardiography has been used as a global evaluation of left ventricular (LV) or right ventricular (RV) function and dimensions. Recently, speckle tracking strain (ST) has provided an analysis of regional RV and LV function. Thus, the intention of the study was to carefully evaluate cardiac function in a group of former world class swimmers applying longitudinal strain (LS) and circumferential strain (CS) analysis. METHODS: Twelve athletes (45±1.5 years) of a former training group involved in high intensity endurance training were examined 24.9±4.3 years after the end of their active swimming career. An echocardiography was performed and LV function was analyzed based on CS and LS. Also, LS was evaluated for the RV. All measurements were performed for epicardium and endocardium independently. RESULTS: Mean LV endocardial LS was -20.0±6.3 and epicardial LS -20.2±6.2. LV endocardial CS was -21.3±8.0 and epicardial CS -11.9±4.2. RV endocardial LS had a mean value of -26.4±6.1 and epicardial LS of -28.2±5.6. CONCLUSION: Twenty-five years after the cessation of endurance training, there was no evidence of a deterioration of RV or LV function as values for RV and LV strain measurements were within normal ranges.

Biomarkers in outpatient heart failure management; Are they correlated to and do they influence clinical judgment?

AIMS: Heart failure (HF) management is complicated by difficulties in clinical assessment. Biomarkers may help guide HF management, but the correspondence between clinical evaluation and biomarker serum levels has hardly been studied. We investigated the correlation between biomarkers and clinical signs and symptoms, the influence of patient characteristics and comorbidities on New York Heart Association (NYHA) classification and the effect of using biomarkers on clinical evaluation. METHODS AND RESULTS: This post-hoc analysis comprised 622 patients (77 ± 8 years, 76 % NYHA class ≥3, 80 % LVEF ≤45 %) participating in TIME-CHF, randomising patients to either NT-proBNP-guided or symptom-guided therapy. Biomarker measurements and clinical evaluation were performed at baseline and after 1, 3, 6, 12 and 18 months. NT-proBNP, GDF-15, hs-TnT and to a lesser extent hs-CRP and cystatin-C were weakly correlated to NYHA, oedema, jugular vein distension and orthopnoea (ρ-range: 0.12-0.33; p < 0.01). NT-proBNP correlated more strongly to NYHA class in the NT-proBNP-guided group compared with the symptom-guided group. NYHA class was significantly influenced by age, body mass index, anaemia, and the presence of two or more comorbidities. CONCLUSION: In HF, biomarkers correlate only weakly with clinical signs and symptoms. NYHA classification is influenced by several comorbidities and patient characteristics. Clinical judgement seems to be influenced by a clinician's awareness of NT-proBNP concentrations.

Insights into atrial fibrillation.

Atrial fibrillation is the most common clinically relevant heart rhythm disorder and is associated with increased morbidity and mortality. Most important risk factors for atrial fibrillation are high age, arterial hypertension, diabetes mellitus, heart failure and rheumatic heart disease. Chronic atrial fibrillation is classified as paroxysmal, persistent, long-standing persistent and permanent atrial fibrillation. Spontaneous conversion to sinus rhythm is observed in paroxysmal atrial fibrillation, whereas in persistent atrial fibrillation, pharmacological or electrical cardioversion is required in order to restore sinus rhythm. In permanent atrial fibrillation, the arrythmia is accepted by patient and physician and cardioversion is not attempted. Rate control only is thus applied in permanent atrial fibrillation, whereas in paroxysmal and persistent atrial fibrillation, addition rhythm control with anti-arrhythmic drugs and/or ablation is attempted if symptoms persist and age and co-morbidities do not pose contra-indications. Besides rhythm management, oral anticoagulation is the mainstay of therapy for most patients with atrial fibrillation. Risk scores such as the CHA2DS2-VASc score help to identify patients with a high risk of stroke and need for oral anticoagulation. The underuse of vitamin K antagonists in clinical practise is partly due to considerable disadvantages: an increased bleeding risk, a narrow therapeutic window and multiple drug interactions prompting frequent laboratory controls to assess an individual dosage. New oral anticoagulants targeting thrombin (dabigatran) or factor Xa (rivaroxaban, apixaban and edoxaban) may replace warfarin in many patients with atrial fibrillation due to convincing data both on efficacy and safety as well as convenience. However, challenges remain with respect to lack of specific antidotes and high costs.

A dedicated cardioversion unit for the treatment of atrial fibrillation. Reducing costs by optimizing processes.

BACKGROUND: Atrial fibrillation (AF) is the most frequent arrhythmia seen in man. Many patients are admitted to the hospital to undergo transesophageal echocardiography (TEE) for thrombus exclusion and subsequent electrical cardioversion (ECV) under deep sedation to restore sinus rhythm. The present study investigated prospectively how workflow optimization can contribute to reducing time and costs in AF patients scheduled for ECV in an outpatient setting. METHODS: A cardioversion unit (CU) was established and equipped to perform all ECV-associated procedures. Between November 2007 and January 2009, ECV was performed in 115 patients in an outpatient setting. Three different settings were tested for ECV: (1) usual care (n = 19): preparation/follow-up in the outpatient clinic, blood testing in the central hospital laboratory (CHL), TEE in the echocardiography laboratory, and ECV in the intensive care unit; (2) optimized process 1 (n = 41): preparation/follow-up, TEE + ECV during one sedation in the CU, blood testing in the CHL; (3) optimized process 2 (n = 55): preparation/follow-up, TEE + ECV and point of care (POC) blood testing in the CU. All procedure-related costs were listed and classified according to material, human resources, and infrastructure. RESULTS: From setting 1 to 3, there was a significant decrease in procedural time from 480 ± 105 min to 205 ± 85 min (p < 0.001). Likewise, ECV-associated costs could be reduced from 683 ± 104  to 299 ± 63  (p < 0.001). CONCLUSION: Establishing a CU for AF enables a more than 50% reduction in procedural time and costs. A combination of TEE and ECV in one sedation and POC testing in the CU were the major contributors to this time and cost reduction.

Moderate physical exercise: a simplified approach for ventricular rate control in older patients with atrial fibrillation.

AIMS: This prospective pilot-study was performed to assess whether regular moderate physical activity elevates the parasympathetic tone to the atrio-ventricular node and decreases VR during permanent AF. BACKGROUND: Adequate ventricular rate (VR) control in patients with permanent atrial fibrillation (AF) is not easy to accomplish. METHODS: 10 patients (mean age 59 +/- 10 years) with permanent AF (duration: 10 +/- 8 years) underwent moderate physical exercise adjusted to their individual physical capability (45 min walking/jogging twice a week). To analyze VR control physical exercise tests and Holter-ECG recordings were performed before and after 4 months. In addition, stepwise lactate tests and psycho-pathometric examinations were obtained. RESULTS: After 4 months of training, there was a trend toward a decrease of mean VR in 24 h Holter-ECGs by 12% from 76 +/- 20 to 67 +/- 12 bpm (P = 0.05) while there was no significant decrease of the minimal VR (38 +/- 8 vs. 36.3 +/- 4.5 bpm, P = 0.54). At a lactate threshold of 2 mmol/l there was a trend towards an increase of the running speed from 105 +/- 11 to 116 +/- 12 m/min (P = 0.05). A significant VR decrease of 8% (range 5-10%) was observed at almost all exercise levels during exercise treadmill testing. Increases of exercise capacity and decreases of VR were accompanied by subjective improvements of health perception. CONCLUSION: Regular moderate physical activity decreases VR at rest and during exercise while increasing exercise capacity. Physical training should be taken into account for ventricular rate control during AF.

MDCT angiography of the pulmonary arteries: intravascular contrast enhancement does not depend on iodine concentration when injecting equal amounts of iodine at standardized iodine delivery rates.

To compare the impact of iodine concentration using two different contrast materials (CM) at standardized iodine delivery rate (IDR) and overall iodine load in 16-multidetector-row-CT-angiography (MDCTA) of the pulmonary arteries of 192 patients with known or suspected pulmonary embolism. One hundred three patients (group A) received 148 ml of a CM containing 300 mg iodine/ml (Ultravist 300, BayerScheringPharma) at a flow rate of 4.9 ml/s. Eighty-nine patients (group B) received 120 ml of a CM with a concentration of 370 mg iodine/ml (Ultravist 370) at a flow rate of 4.0 ml/s, resulting in a standardized IDR (approximately 1.5 gI/s) and the same overall amount of iodine (44.4 g). Both CM injections were followed by a saline chaser. Mean density values were determined in the pulmonary trunk, the ascending and the descending aorta, respectively. Applying repeated-measures ANOVA, no statistically significant differences between both MDCTA protocols were found (p = 0.5790): the mean density in the pulmonary trunk was 355 +/- 116 Hounsfield Units (group A) and 358 +/- 115 (group B). The corresponding values for the ascending and descending aorta were 295 +/- 79 (group A) and 284 +/- 65 (group B) as well as 272 +/- 71 and 262 +/- 70. In conclusion, the use of standardized IDR and overall iodine load provides comparable intravascular CM density in pulmonary 16-MDCTA for delivering contrast materials with different iodine concentrations.

The role of intracardiac echocardiography in interventional electrophysiology.

Visualization of the cardiac anatomy becomes more and more important as the complexity of interventions increases. Intracardiac echocardiography (ICE) provides good depiction of cardiac soft tissue structures and has become an important tool in today's cardiology. It has been shown to be valuable during many ablation procedures for supraventricular and ventricular arrhythmias. ICE has been used for monitoring catheter placement, observing catheter-tissue contact and lesion formation as well as titrating ablation energy. The rate of complications could be reduced, outcome of procedures improved and radiation exposure decreased. Even more, new therapy strategies have been evaluated based on ICE and it has also been used in the setting of three- dimensional imaging and image integration.

Telephonic transmission of 12-lead electrocardiograms during acute myocardial infarction.

To test the feasibility of a small and simple system for telephonic transmission of 12-lead electrocardiograms (ECGs), 70 patients with acute coronary syndrome admitted to the cardiac care unit (CCU) were included in a feasibility study. The transmission system consisted of a belt with multiple electrodes, which was positioned around the chest. The ECG signal was sent to a call centre via a standard telephone line. In parallel, a standard 12-lead ECG was recorded on site. In a retrospective analysis, each lead of the transmitted ECG was compared with the on-site 12-lead ECG with regard to ST-segment changes and final diagnosis. In all 37 patients with acute ST-elevation myocardial infarction, the diagnosis was correctly established on the basis of telephone-transmitted ECGs. In 96% of limb and 88% of chest leads, ST elevations which were visible in standard ECGs were correctly displayed on telephonically transmitted ECGs. In the remaining 33 patients no false-positive diagnosis was made using transtelephonic ECG analysis. A control group of 31 patients without apparent heart disease showed high concordance between standard ECGs and telephonically transmitted ECGs. Telephonically transmitted 12-lead ECGs interpreted by a hospital-based internist/cardiologist might allow a rapid and accurate diagnosis of ST-elevation myocardial infarction and may increase diagnostic safety for the emergency staff during prehospital decision making and treatment of acute myocardial infarction.

[Hypokalemic paralysis with thyrotoxicosis]. / Hypokaliämische Lähmung bei Hyperthyreose.

Hypokalemic periodic paralysis as a complication of thyrotoxicosis (thyrotoxic periodic paralysis) most often occurs in east Asian men. It is characterised by recurrent episodes of flaccid paralysis, hypokalemia, and underlying hyperthyroidism. It needs to be distinguished from sporadic and familial forms of periodic hypokalemic paralysis. No disturbances in the acid-base state and no extracorporal potassium loss are present. We report on the typical case of a young Chinese man presenting with hypokalemic periodic paralysis associated with yet unknown Graves' disease. Intravenous substitution of potassium and oral propranolol were administered. Complete remission was achieved after 10 hours. After medical therapy had normalised thyroid hormone levels, no further hypokalemic paralytic attacks occurred.

Catheter stimulation of cardiac parasympathetic nerves in humans: a novel approach to the cardiac autonomic nervous system.

BACKGROUND: Cardiac parasympathetic nerves run alongside the superior vena cava (SVC) and accumulate particularly epicardially adjacent to the orifice of the coronary sinus (CS). In animals, these nerves can be electrically stimulated inside the SVC or CS, which results in negative chronotropic/dromotropic effects and negative inotropic effects in the atria but not the ventricles. Parasympathetic nerve stimulation (PS) with 20 Hz in the CS, however, also excites the atria, thereby inducing atrial fibrillation. The present study overcomes this limitation by applying high-frequency nerve stimuli within the atrial refractory period. Using this technique, we investigated for the first time whether neurophysiological effects similar to those in animals can be obtained in humans. METHODS AND RESULTS: In 25 patients, parasympathetic nerves were stimulated via a multipolar electrode catheter placed in the SVC (stimulation with 20 Hz; n=14) or CS (pulsed 200-Hz stimuli; n=11). A significant sinus rate decrease and prolongation of the antegrade Wenckebach period was achieved during PS in the SVC. During PS in the CS, a graded-response prolongation of the antegrade Wenckebach interval was observed with increasing PS voltage until third-degree AV block occurred in 8 of 11 patients. The negative chronotropic/dromotropic effects started and terminated immediately after the onset and termination of PS, respectively. Atropine abolished these effects (n=11). CONCLUSIONS: Human parasympathetic efferent nerve stimulation induces reversible negative chronotropic and dromotropic effects. PS may serve as an adjunctive tool for the diagnosis/treatment of supraventricular tachycardias and may be beneficial for ventricular rate slowing during tachycardic atrial fibrillation in patients with congestive heart failure.