The risk of QTc-interval prolongation in COVID-19 patients treated with chloroquine.

BACKGROUND: Chloroquine, a quinolone antimalarial drug, is known to potentially inhibit pH-dependent viral replication of the SARS-CoV­2 infection. Therefore, chloroquine is considered as a treatment option for coronavirus disease 2019 (COVID-19). Chloroquine is known for prolonging the QT interval, but limited data are available on the extent of this QT-prolonging effect. OBJECTIVE: To assess the QTc-prolonging potential of chloroquine in COVID-19 patients and to evaluate whether this prolongation increases with the cumulative dose of chloroquine and is associated with the peak plasma concentration of chloroquine. Furthermore, the number of patients who prematurely discontinued treatment or had an adjustment in dose due to QTc-interval prolongation was established. METHODS: A retrospective, observational study was performed in patients aged over 18 years, hospitalised for a suspected or proven infection with COVID-19, and therefore treated with chloroquine, with a baseline electrocardiogram (ECG) performed prior to the start of treatment and at least one ECG after starting the treatment. RESULTS: In total, 397 patients were included. The mean increase in QTc interval throughout the treatment with chloroquine was 33 ms. Nineteen out of 344 patients unnecessarily had their treatment prematurely discontinued or adjusted due to a prolonged QTc interval based on the computerised interpretation of the ECG. CONCLUSION: Chloroquine treatment in COVID-19 patients gradually increased the QTc interval. Due to a significant number of overestimated QTc intervals by computer analysis, it is advisable to measure the QTc interval manually before adjusting the dose or withdrawing this potentially beneficial medication.

Atom-Chip Fountain Gravimeter.

We demonstrate a quantum gravimeter by combining the advantages of an atom chip for the generation, delta-kick collimation, and coherent manipulation of freely falling Bose-Einstein condensates (BECs) with an innovative launch mechanism based on Bloch oscillations and double Bragg diffraction. Our high-contrast BEC interferometer realizes tens of milliseconds of free fall in a volume as little as a one centimeter cube and paves the way for measurements with sub-µGal accuracies in miniaturized, robust devices.

Double Bragg Interferometry.

We employ light-induced double Bragg diffraction of delta-kick collimated Bose-Einstein condensates to create three symmetric Mach-Zehnder interferometers. They rely on (i) first-order, (ii) two successive first-order, and (iii) second-order processes which demonstrate the scalability of the corresponding momentum transfer. With respect to devices based on conventional Bragg scattering, these symmetric interferometers double the scale factor and feature a better suppression of noise and systematic uncertainties intrinsic to the diffraction process. Moreover, we utilize these interferometers as tiltmeters for monitoring their inclination with respect to gravity.

Interferometry with Bose-Einstein condensates in microgravity.

Atom interferometers covering macroscopic domains of space-time are a spectacular manifestation of the wave nature of matter. Because of their unique coherence properties, Bose-Einstein condensates are ideal sources for an atom interferometer in extended free fall. In this Letter we report on the realization of an asymmetric Mach-Zehnder interferometer operated with a Bose-Einstein condensate in microgravity. The resulting interference pattern is similar to the one in the far field of a double slit and shows a linear scaling with the time the wave packets expand. We employ delta-kick cooling in order to enhance the signal and extend our atom interferometer. Our experiments demonstrate the high potential of interferometers operated with quantum gases for probing the fundamental concepts of quantum mechanics and general relativity.

Long-term prognosis of patients with cardiac syndrome X: a review.

AIMS: Follow-up studies of patients with cardiac syndrome X (CSX) generally report good prognosis. However, some recent studies report an adverse outcome for women. METHODS AND RESULTS: Structured literature search and meta-analysis for studies regarding prognosis of cardiac syndrome X patients. We identified 85 studies, ultimately selecting 16 for inclusion. Meta-analysis yielded a pooled major cardiac event percentage of 1.5% per 5 years and a pooled vascular event percentage of 4.8% per 5 years (n = 16 studies, n = 1694 patients). Fourteen studies reported upon the recurrence rate of angina pectoris: the pooled percentage of angina recurrence was 55% (n = 1336 patients). CONCLUSION: The present review of recent archival literature demonstrates an overall major cardiac event rate of 1.5% per 5 years. Although this is an excellent prognosis for CSX patients, the quality of life is impaired because of the high recurrence rate of angina pectoris (55%).

Bose-Einstein condensation in microgravity.

Albert Einstein's insight that it is impossible to distinguish a local experiment in a "freely falling elevator" from one in free space led to the development of the theory of general relativity. The wave nature of matter manifests itself in a striking way in Bose-Einstein condensates, where millions of atoms lose their identity and can be described by a single macroscopic wave function. We combine these two topics and report the preparation and observation of a Bose-Einstein condensate during free fall in a 146-meter-tall evacuated drop tower. During the expansion over 1 second, the atoms form a giant coherent matter wave that is delocalized on a millimeter scale, which represents a promising source for matter-wave interferometry to test the universality of free fall with quantum matter.

Left ventricular beat to beat performance in atrial fibrillation: dependence on contractility, preload, and afterload.

OBJECTIVE: To assess independent determinants of beat to beat variation in left ventricular performance during atrial fibrillation. DESIGN: Prospective study. SETTING: University hospital. PATIENTS: Seven patients with chronic non-valvar atrial fibrillation. INTERVENTIONS: Invasive and non-invasive haemodynamic variables were assessed using a non-imaging computerised nuclear probe, a balloon tipped flow directed catheter, and a non-invasive fingertip blood pressure measurement system linked to a personal computer. MAIN OUTCOME MEASURES: Left ventricular ejection fraction, left ventricular volume, ventricular cycle length, pulmonary capillary wedge pressure, and measures of left ventricular afterload (end systolic pressure/stroke volume) and contractility (end systolic pressure/end systolic volume) were calculated on a beat to beat basis during 500 consecutive RR intervals. A statistical model of the beat to beat variation of the ejection fraction containing these variables was constructed by multiple regression analysis. RESULTS: Positive independent relations with ejection fraction were found for preceding RR interval, contractility, and end diastolic volume, while inverse relations were found for afterload, preceding end systolic volume, and preceding contractility (all variables, p < 0. 0001). A relatively strong interaction was found between end diastolic volume and afterload, indicating that ejection fraction was relatively more enhanced by preload in the presence of low afterload. CONCLUSIONS: The varying left ventricular systolic performance during atrial fibrillation is independently influenced by beat to beat variation in cycle length, preload, afterload, and contractility. Beat to beat variation in preload shows its effect on ventricular performance mainly in the presence of a low afterload.

Quantification of the atrial contribution to diastolic filling during radionuclide angiography.

To define exactly the onset of late diastolic filling with respect to atrial contraction, the atrial contribution (AC) to left ventricular filling was quantified in 34 patients with a variety of diseases using radionuclide angiography. From the time-activity curve and its first derivative, a flow-volume loop was constructed. Using the flow-volume loop, the period between minimal flow and the moment of maximal end-diastolic counts was defined as the AC-interval and correlated with the PQ-interval on the electrocardiogram. The relative filling volumes within these time periods were closely related in all patients (r = 0.99, P < 0.0001). The correlation between the PQ-interval and AC-interval was also statistically significant (r = 0.82, P < 0.0001). In a subset of patients, the PQ-interval and AC-interval were not exactly the same. In these patients, the AC-interval was always longer than the PQ-interval, indicating the existence of passive diastasis flow before the onset of atrial contraction. This was more apparent in patients with low heart rates than in those with high heart rates. Despite the close correlation between the PQ-interval on the electrocardiogram and the AC-interval of the flow-volume loop, they may represent different entities. We conclude that the PQ-interval is better than the AC-interval for determining the moment of onset of atrial activity during radionuclide angiography.

Normal values and reproducibility of left ventricular filling parameters by radionuclide angiography.

BACKGROUND: In physiologic situations age, heart rate (HR) and left ventricular ejection fraction (EF) may influence left ventricular filling rate. In this study, we determined normal values for radionuclide angiography (RNA) derived diastolic filling parameters, the correlations with age, HR and EF and their reproducibility. METHODS: The study was performed in 20 patients, 40-76 years old (mean 57), with normal findings at coronary angiography and left ventriculography. The first RNA was performed at rest (RNA1). Then, five minutes bicycle ergometry was performed and the patients were allowed five minutes rest before RNA was repeated (RNA2). From the left ventricular time activity curve we determined peak filling rate (PFR), time to peak filling rate (TPFR) and atrial contribution (AC) to ventricular filling. RESULTS: Values for PFR1 were 2.2 +/- 0.6 EDV/sec (PFR2 2.4 +/- 0.7 EDV/sec, r = 0.82), for TPFR1 198 +/- 22 msec (TPFR2 203 +/- 24 msec, r = 0.45) and for AC1 31 +/- 11% (AC2 31 +/- 10%, r = 0.72). The correlations of PFR and TPFR with age were statistically significant (respectively r = -0.68 and r = 0.48, P < 0.05). PFR was also influenced by HR and EF (resp. r = 0.51 and r = 0.50, P < 0.05). TPFR however was not influenced by HR and EF, whereas AC was positively correlated with HR (r = 0.79, P < 0.01). CONCLUSIONS: Radionuclide angiography is a reliable and reproducible method to assess parameters of diastolic left ventricular filling in individual patients. It may therefore be used to serially follow diastolic function. When used for interindividual comparison the dependency of RNA derived left ventricular filling parameters on age, HR and EF should however be considered.

Effect of mibefradil on left ventricular diastolic function in patients with congestive heart failure.

Calcium antagonists have antihypertensive and antianginal properties. In heart failure, however, their use can be hazardous, as systolic function can deteriorate. This may not be true of the new calcium antagonist mibefradil, which has a new chemical structure. Calcium antagonists may also be beneficial for diastolic left ventricular function in coronary artery disease. To investigate the possible effects of mibefradil on diastolic left ventricular function, we performed the present study as a multicenter, double-blind,placebo-controlled, multiple-dose safety trial. Fifteen patients with New York Heart Association (NYHA) class II or III for dyspnea and depressed ejection fraction (<40%) due to a previous myocardial infarction were investigated. The measured nuclear angiographic parameters included ejection fraction (EF), peak ejection rate (PER), and peak filling rate (PFR). Systolic and diastolic blood pressure (SBP, DBP) and heart rate (HR) were also obtained. Group I (5 patients) received placebo medication; group IIA (6 patients) received mibefradil 6.25, 12.5, or 25 mg/day; and group IIB (4 patients) received mibefradil 50 or 100 mg/day. Measurements were made before and after the first dose and after 1 week of treatment before and after the final dose. Mibefradil clearly decreased HR (repeated-measures analysis of variance p < 0.05). No statistically significant effects of mibefradil were noted on SBP or DBP or on systolic and diastolic left ventricular function. In our study conditions, mibefradil caused no worsening of systolic function and preserved diastolic function in short-term treatment of patients with decreased EF and heart failure.