ArticleCardiovascular research2017
Hierarchical statistical techniques are necessary to draw reliable conclusions from analysis of isolated cardiomyocyte studies.
Article in Cardiovascular research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 109 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
109 citing papers in PubMed, 143 citations in OpenAlex.
- Chamber-specific regulation of myofilament Ca2+ sensitivity by nNOSβ via troponin I phosphorylation: Predominance in the right ventricle.The Journal of general physiology · 2026Article
- Excessive EFHD1-dependent ER-mitochondrial contacts drive a maladaptive antiviral response in metabolic liver disease.The Journal of clinical investigation · 2026Article
- The β1 adrenoceptor (AR) blocker metoprolol normalises βAR cascade and caveolar protein expression and restores β1AR responsiveness in failing right ventricular myocytes.Journal of molecular and cellular cardiology plus · 2026Article
- Metabolic crisis and TRPM4 activation cause QT prolongation in TANGO2 deficiency disorder.Cardiovascular research · 2026Article
- NUAK1 Inhibition Alleviates Ischemia-Reperfusion Injury via SYNE1-YAP1.Circulation research · 2026Article
- Cardiomyocyte-Specific Plakophilin-2 Loss Is Sufficient to Induce Aging and Senescence of Nonmyocytes: Relevance to Arrhythmogenic Cardiomyopathy.Journal of the American Heart Association · 2026Article
- D801N in ATP1A3-encoded Na/K-ATPase alpha 3 causes cardiac arrhythmogenesis through sodium-calcium exchanger-mediated calcium overload.JCI insight · 2026Article
- Spastin-mediated severing of glutamylated microtubules controls cardiomyocyte coupling.Nature cardiovascular research · 2026Article
- Mechano-electrical feedback in transgenic rabbit models of long QT syndrome Type 2 and short QT syndrome Type 1.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2026Article
- High Burden of Premature Ventricular Contractions Upregulates Transcriptional Markers of Inflammation and Promotes Adverse Cardiac Remodeling Linked to Cardiomyopathy.Circulation. Arrhythmia and electrophysiology · 2026Article
- A modification of retrograde Langendorff-perfusion to increase the yield of CaFrontiers in pharmacology · 2026Article
- Increased Intermembrane Space [CaCirculation research · 2025Article
- The CNP analogue vosoritide mediates PDE2-sensitive anti-arrhythmogenic effects in mouse hearts with STZ-induced type 1 diabetes.Basic research in cardiology · 2025Article
- In PLN-R14del mice, SR structure restoration, rather than calcium cycling, is the dominant effector of PLN-ASO treatment.Cardiovascular research · 2025Article
- Exercise-induced dysregulation of the adrenergic response in a mouse model of PKP2-arrhythmogenic cardiomyopathy.Heart rhythm · 2025Article
- Stretch-Induced Increase in CaJournal of the American Heart Association · 2025Article
- Inhibition of tenascin C rescues abnormally reduced Na currents in dystrophin-deficient ventricular cardiomyocytes.American journal of physiology. Heart and circulatory physiology · 2025Article
- Beneficial action potential duration-shortening effects, but deleterious negative inotropism of IKs-activator docosahexaenoyl glycine in long QT syndrome type 2.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2025Article
- The sodium/glucose cotransporter 2 inhibitor empagliflozin is a pharmacological chaperone of cardiac NaAmerican journal of physiology. Heart and circulatory physiology · 2025Article
- Atrial cardiomyopathy resulting from loss of plakophilin-2 expression: Response to adrenergic stimulation and implications for the exercise response.The Journal of physiology · 2025Article
49 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
aimsIt is generally accepted that post-MI heart failure (HF) changes a variety of aspects of sarcoplasmic reticular Ca2+ fluxes but for some aspects there is disagreement over whether there is an increase or decrease. The commonest statistical approach is to treat data collected from each cell as independent, even though they are really clustered with multiple likely similar cells from each heart. In this study, we test whether this statistical assumption of independence can lead the investigator to draw conclusions that would be considered erroneous if the analysis handled clustering with specific statistical techniques (hierarchical tests). METHODS AND
resultsCa2+ transients were recorded in cells loaded with Fura-2AM and sparks were recorded in cells loaded with Fluo-4AM. Data were analysed twice, once with the common statistical approach (assumption of independence) and once with hierarchical statistical methodologies designed to allow for any clustering. The statistical tests found that there was significant hierarchical clustering. This caused the common statistical approach to underestimate the standard error and report artificially small P values. For example, this would have led to the erroneous conclusion that time to 50% peak transient amplitude was significantly prolonged in HF. Spark analysis showed clustering, both within each cell and also within each rat, for morphological variables. This means that a three-level hierarchical model is sometimes required for such measures. Standard statistical methodologies, if used instead, erroneously suggest that spark amplitude is significantly greater in HF and spark duration is reduced in HF.
conclusionCa2+ fluxes in isolated cardiomyocytes show so much clustering that the common statistical approach that assumes independence of each data point will frequently give the false appearance of statistically significant changes. Hierarchical statistical methodologies need a little more effort, but are necessary for reliable conclusions. We present cost-free simple tools for performing these analyses.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.