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Advanced Drug Delivery Reviews 2020Modeling of human organs has long been a task for scientists in order to lower the costs of therapeutic development and understand the pathological onset of human...
Modeling of human organs has long been a task for scientists in order to lower the costs of therapeutic development and understand the pathological onset of human disease. For decades, despite marked differences in genetics and etiology, animal models remained the norm for drug discovery and disease modeling. Innovative biofabrication techniques have facilitated the development of organ-on-a-chip technology that has great potential to complement conventional animal models. However, human organ as a whole, more specifically the human heart, is difficult to regenerate in vitro, in terms of its chamber specific orientation and its electrical functional complexity. Recent progress with the development of induced pluripotent stem cell differentiation protocols, made recapitulating the complexity of the human heart possible through the generation of cells representative of atrial & ventricular tissue, the sinoatrial node, atrioventricular node and Purkinje fibers. Current heart-on-a-chip approaches incorporate biological, electrical, mechanical, and topographical cues to facilitate tissue maturation, therefore improving the predictive power for the chamber-specific therapeutic effects targeting adult human. In this review, we will give a summary of current advances in heart-on-a-chip technology and provide a comprehensive outlook on the challenges involved in the development of human physiologically relevant heart-on-a-chip.
Topics: Drug Discovery; Heart; Humans; Induced Pluripotent Stem Cells; Lab-On-A-Chip Devices; Microtechnology; Myocytes, Cardiac; Tissue Engineering
PubMed: 31917972
DOI: 10.1016/j.addr.2019.12.002 -
Therapeutic Hypothermia and Temperature... Mar 2020The beneficial effect of sinus bradycardia during targeted temperature management (TTM) in cardiac arrest patients remains doubtful. We aimed to investigate the impact... (Meta-Analysis)
Meta-Analysis
The beneficial effect of sinus bradycardia during targeted temperature management (TTM) in cardiac arrest patients remains doubtful. We aimed to investigate the impact of sinus bradycardia on survival and neurological outcome. MEDLINE (PubMed), Cochrane, Google Scholar, and ClinicalTrials.gov databases were searched for studies reporting on comatose postcardiac arrest patients presenting sinus bradycardia during TTM. Outcomes were the 180-day survival and final neurologic function assessed by the Cerebral Performance Category scale. The effect size on study outcomes is presented as odds ratio (OR) with 95% confidence interval (CI). Two studies with 681 patients were included. Compared to no-sinus bradycardia group, in patients with sinus bradycardia below 50 bpm, a significant effect of sinus bradycardia on reduction of 180-day mortality was reported (OR = 0.42; 95% CI: 0.29-0.59). No heterogeneity was detected. Sinus bradycardia below 50 bpm during TTM may be protective and should be considered in comatose postcardiac arrest patients.
Topics: Atrioventricular Node; Body Temperature; Bradycardia; Humans; Hypothermia, Induced
PubMed: 31660784
DOI: 10.1089/ther.2019.0027 -
Journal of Arrhythmia Apr 2019Atrial fibrillation (AF) among patients with heart failure with reduced ejection fraction (HFrEF) is associated with adverse clinical outcomes. Our primary aim was to...
BACKGROUND
Atrial fibrillation (AF) among patients with heart failure with reduced ejection fraction (HFrEF) is associated with adverse clinical outcomes. Our primary aim was to evaluate patient-centered outcomes and surrogate outcomes following catheter ablation (CA) of AF among patients with HFrEF compared to standard medical therapy with or without device therapy (atrioventricular node ablation and cardiac resynchronization therapy).
METHODS
A systematic literature review was performed limiting our searches to randomized control trials reporting outcomes of CA compared to standard medical therapy with or without device therapy were included. Patient-centered outcomes were relative reduction in all-cause mortality, heart failure readmissions, and recurrence of AF. Surrogate outcomes of interest were change in ejection fraction, change in peak oxygen consumption, reduction in brain natriuretic peptide levels, change in 6-minute walk distance, and change in Minnesota living with heart failure score.
RESULTS
Seven randomized control trials (Patient n = 721) met our inclusion criteria. All trials used radiofrequency energy for CA of AF. CA for AF was associated with significantly lower all-cause mortality (Risk ratio [RR] = 0.52, 95% confidence interval [CI] = 0.35-0.76, = 0.001, = 0%), lower rate of heart failure readmission (RR = 0.58, 95% CI = 0.46-0.74, < 0.001, = 0%) and lower rate of AF recurrence (RR = 0.33, 95% CI = 0.22-0.50, < 0.001, = 68%) as compared to standard medical therapy. Surrogate outcomes showed a similar benefit favoring CA.
CONCLUSION AND RELEVANCE
Catheter ablation for AF in HFrEF is associated with improvement in patient-centered outcomes and surrogate outcomes when compared to standard medical therapy with or without device therapy.
PubMed: 31007780
DOI: 10.1002/joa3.12146 -
Circulation Aug 2019It is unclear whether physiologic pacing by either cardiac biventricular pacing (BiVP) or His bundle pacing (HisBP) may prevent adverse structural and functional... (Meta-Analysis)
Meta-Analysis
Impact of Physiologic Pacing Versus Right Ventricular Pacing Among Patients With Left Ventricular Ejection Fraction Greater Than 35%: A Systematic Review for the 2018 ACC/AHA/HRS Guideline on the Evaluation and Management of Patients With Bradycardia and Cardiac Conduction Delay: A Report of the...
BACKGROUND
It is unclear whether physiologic pacing by either cardiac biventricular pacing (BiVP) or His bundle pacing (HisBP) may prevent adverse structural and functional consequences known to occur among some patients who receive right ventricular pacing (RVP).
AIM
Our analysis sought to review existing literature to determine if BiVP and/or HisBP might prevent adverse remodeling and be associated with structural, functional, and clinical advantages compared with RVP among patients without severe left ventricular dysfunction (>35%) who required permanent pacing because of heart block.
METHODS
A literature search was conducted using MEDLINE (through PubMed) and Embase to identify randomized trials and observational studies comparing the effects of BiVP or HisBP versus RVP on measurements of left ventricular dimensions, left ventricular ejection fraction (LVEF), heart failure functional classification, quality of life, 6-minute walk, hospitalizations, and mortality. Data from studies that met the appropriate population, intervention, comparator, and outcomes of interest were abstracted for meta-analysis. Studies that reported pooled outcomes among patients with LVEF both above and below 35% could not be included in the meta-analysis because of strict relationships with industry procedures that preclude retrieval of industry-retained unpublished data on the subset of patients with preserved left ventricular function.
RESULTS
Evidence from 8 studies, including a total of 679 patients meeting the prespecified criteria for inclusion, was identified. Results were compared for BiVP versus RVP, HisBP versus RVP, and BiVP+HisBP versus RVP. Among patients who received physiologic pacing with either BiVP or HisBP, the LV end-diastolic and end-systolic volumes were significantly lower (mean duration of follow-up: 1.64 years; -2.77 mL [95% CI -4.37 to -1.1 mL]; P=0.001; and -7.09 mL [95% CI -11.27 to -2.91; P=0.0009) and LVEF remained preserved or increased (mean duration of follow-up: 1.57 years; 5.328% [95% CI: 2.86%-7.8%; P<0.0001). Data on clinical impact such as functional status and quality of life were not definitive. Data on hospitalizations were unavailable. There was no effect on mortality. Several studies stratified results by LVEF and found that patients with LVEF >35% but ≤52% were more likely to receive benefit from physiologic pacing. Patients with chronic atrial fibrillation who underwent atrioventricular node ablation and pacemaker implant demonstrated clear improvement in LVEF with BiVP or HisBP versus RVP.
CONCLUSION
Among patients with LVEF >35%, the LVEF remained preserved or increased with either BiVP or HisBP compared with RVP. However, patient-centered clinical outcome improvement appears to be limited primarily to patients who have chronic atrial fibrillation with rapid ventricular response rates and have undergone atrioventricular node ablation.
Topics: Atrial Fibrillation; Bradycardia; Cardiac Conduction System Disease; Cardiac Pacing, Artificial; Humans; Practice Guidelines as Topic; Quality of Life; Stroke Volume; Ventricular Function, Left
PubMed: 30586773
DOI: 10.1161/CIR.0000000000000629 -
Pacing and Clinical Electrophysiology :... Feb 2019Cardiac resynchronization therapy (CRT) is the standard-of-care therapy for the patients with heart failure and left ventricular (LV) dyssynchrony. However,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Cardiac resynchronization therapy (CRT) is the standard-of-care therapy for the patients with heart failure and left ventricular (LV) dyssynchrony. However, approximately 30% of the patients show no response. Recent studies have shown that His bundle pacing (HBP) could be an alternative for the patients with CRT indications. The purpose of this study was to evaluate the efficacy of HBP in patients with heart failure.
METHODS
We searched PubMed and Embase databases for studies evaluating HBP in patients with heart failure and LV dyssynchrony. The successful rate of implantation, QRS duration, pacing threshold, LV function at baseline and follow-up, and mortality rates were extracted and summarized.
RESULTS
Eleven studies including 494 patients were included in this analysis. The overall successful rate for implantation was 82.4%. The main indications for HBP were CRT candidates and cardiomyopathy with atrial fibrillation undergoing atrioventricular node ablation. Permanent HBP resulted in narrow QRS duration of 116.3 ± 13.9 ms after implantation. LV functions, including echocardiographic parameters and clinical outcomes, significantly improved at follow-up (P < 0.001). However, there was a trend of increased capture and bundle branch block correction thresholds at follow-up compared to baseline (P = 0.01 and 0.02, respectively). During a mean follow-up of 23.7 months, 5.9% of the patients experienced heart failure-related hospitalization and the mortality rate was 9.1%.
CONCLUSION
Permanent HBP has shown promising results for heart failure patients in small observational studies. Randomized controlled trials are needed to assess the efficacy of HBP in these patients.
Topics: Bundle of His; Cardiac Pacing, Artificial; Heart Failure; Humans
PubMed: 30515877
DOI: 10.1111/pace.13565 -
Heart Rhythm Sep 2019It is unclear whether physiologic pacing by either cardiac biventricular pacing (BiVP) or His bundle pacing (HisBP) may prevent adverse structural and functional...
Impact of physiologic pacing versus right ventricular pacing among patients with left ventricular ejection fraction greater than 35%: A systematic review for the 2018 ACC/AHA/HRS guideline on the evaluation and management of patients with bradycardia and cardiac conduction delay: A Report of the...
BACKGROUND
It is unclear whether physiologic pacing by either cardiac biventricular pacing (BiVP) or His bundle pacing (HisBP) may prevent adverse structural and functional consequences known to occur among some patients who receive right ventricular pacing (RVP).
AIM
Our analysis sought to review existing literature to determine if BiVP and/or HisBP might prevent adverse remodeling and be associated with structural, functional, and clinical advantages compared with RVP among patients without severe left ventricular dysfunction (>35%) who required permanent pacing because of heart block.
METHODS
A literature search was conducted using MEDLINE (through PubMed) and Embase to identify randomized trials and observational studies comparing the effects of BiVP or HisBP versus RVP on measurements of left ventricular dimensions, left ventricular ejection fraction (LVEF), heart failure functional classification, quality of life, 6-minute walk, hospitalizations, and mortality. Data from studies that met the appropriate population, intervention, comparator, and outcomes of interest were abstracted for meta-analysis. Studies that reported pooled outcomes among patients with LVEF both above and below 35% could not be included in the meta-analysis because of strict relationships with industry procedures that preclude retrieval of industry-retained unpublished data on the subset of patients with preserved left ventricular function.
RESULTS
Evidence from 8 studies, including a total of 679 patients meeting the prespecified criteria for inclusion, was identified. Results were compared for BiVP versus RVP, HisBP versus RVP, and BiVP+HisBP versus RVP. Among patients who received physiologic pacing with either BiVP or HisBP, the LV end-diastolic and end-systolic volumes were significantly lower (mean duration of follow-up: 1.64 years; -2.77 mL [95% CI -4.37 to -1.1 mL]; p=0.001; and -7.09 mL [95% CI -11.27 to -2.91; p=0.0009) and LVEF remained preserved or increased (mean duration of follow-up: 1.57 years; 5.328% [95% CI: 2.86%-7.8%; p<0.0001). Data on clinical impact such as functional status and quality of life were not definitive. Data on hospitalizations were unavailable. There was no effect on mortality. Several studies stratified results by LVEF and found that patients with LVEF >35% but ≤52% were more likely to receive benefit from physiologic pacing. Patients with chronic atrial fibrillation who underwent atrioventricular node ablation and pacemaker implant demonstrated clear improvement in LVEF with BiVP or HisBP versus RVP.
CONCLUSION
Among patients with LVEF >35%, the LVEF remained preserved or increased with either BiVP or HisBP compared with RVP. However, patient-centered clinical outcome improvement appears to be limited primarily to patients who have chronic atrial fibrillation with rapid ventricular response rates and have undergone atrioventricular node ablation.
Topics: American Heart Association; Bradycardia; Cardiac Conduction System Disease; Cardiac Resynchronization Therapy; Heart Conduction System; Heart Ventricles; Humans; Practice Guidelines as Topic; Stroke Volume; Treatment Outcome; United States; Ventricular Remodeling
PubMed: 30412776
DOI: 10.1016/j.hrthm.2018.10.035 -
Journal of the American College of... Aug 2019It is unclear whether physiologic pacing by either cardiac biventricular pacing (BiVP) or His bundle pacing (HisBP) may prevent adverse structural and functional... (Comparative Study)
Comparative Study
Impact of Physiologic Pacing Versus Right Ventricular Pacing Among Patients With Left Ventricular Ejection Fraction Greater Than 35%: A Systematic Review for the 2018 ACC/AHA/HRS Guideline on the Evaluation and Management of Patients With Bradycardia and Cardiac Conduction Delay: A Report of the...
BACKGROUND
It is unclear whether physiologic pacing by either cardiac biventricular pacing (BiVP) or His bundle pacing (HisBP) may prevent adverse structural and functional consequences known to occur among some patients who receive right ventricular pacing (RVP).
AIM
Our analysis sought to review existing literature to determine if BiVP and/or HisBP might prevent adverse remodeling and be associated with structural, functional, and clinical advantages compared with RVP among patients without severe left ventricular dysfunction (>35%) who required permanent pacing because of heart block.
METHODS
A literature search was conducted using MEDLINE (through PubMed) and Embase to identify randomized trials and observational studies comparing the effects of BiVP or HisBP versus RVP on measurements of left ventricular dimensions, left ventricular ejection fraction (LVEF), heart failure functional classification, quality of life, 6-minute walk, hospitalizations, and mortality. Data from studies that met the appropriate population, intervention, comparator, and outcomes of interest were abstracted for meta-analysis. Studies that reported pooled outcomes among patients with LVEF both above and below 35% could not be included in the meta-analysis because of strict relationships with industry procedures that preclude retrieval of industry-retained unpublished data on the subset of patients with preserved left ventricular function.
RESULTS
Evidence from 8 studies, including a total of 679 patients meeting the prespecified criteria for inclusion, was identified. Results were compared for BiVP versus RVP, HisBP versus RVP, and BiVP+HisBP versus RVP. Among patients who received physiologic pacing with either BiVP or HisBP, the LV end-diastolic and end-systolic volumes were significantly lower (mean duration of follow-up: 1.64 years; -2.77 mL [95% CI -4.37 to -1.1 mL]; p=0.001; and -7.09 mL [95% CI -11.27 to -2.91; p=0.0009) and LVEF remained preserved or increased (mean duration of follow-up: 1.57 years; 5.328% [95% CI: 2.86%-7.8%; p<0.0001). Data on clinical impact such as functional status and quality of life were not definitive. Data on hospitalizations were unavailable. There was no effect on mortality. Several studies stratified results by LVEF and found that patients with LVEF >35% but ≤52% were more likely to receive benefit from physiologic pacing. Patients with chronic atrial fibrillation who underwent atrioventricular node ablation and pacemaker implant demonstrated clear improvement in LVEF with BiVP or HisBP versus RVP.
CONCLUSION
Among patients with LVEF >35%, the LVEF remained preserved or increased with either BiVP or HisBP compared with RVP. However, patient-centered clinical outcome improvement appears to be limited primarily to patients who have chronic atrial fibrillation with rapid ventricular response rates and have undergone atrioventricular node ablation.
Topics: Cardiac Pacing, Artificial; Heart Block; Humans; Stroke Volume; Ventricular Remodeling
PubMed: 30412708
DOI: 10.1016/j.jacc.2018.10.045 -
Heart, Lung & Circulation Nov 2019Post cardiac injury syndrome (PCIS) is a troublesome but not uncommon complication following catheter ablation of arrhythmias. We aimed to study the clinical features of...
BACKGROUND
Post cardiac injury syndrome (PCIS) is a troublesome but not uncommon complication following catheter ablation of arrhythmias. We aimed to study the clinical features of ablation-associated PCIS.
METHODS
For this purpose, we conducted a computerised literature search that identified 19 published cases, and we additionally included another two new cases from our centres. Twenty-one (21) cases of PCIS following ablation were analysed.
RESULTS
Among the 21 cases, PCIS most commonly occurred after atrial flutter/fibrillation (AFL/AF) ablation (71.4%), followed by atrioventricular re-entrant tachycardia (AVRT) ablation (9.5%), atrioventricular node (AVN) ablation (9.5%), atrioventricular nodal re-entrant tachycardia (AVNRT) ablation (4.8%) and ventricular tachycardia (VT) ablation (4.8%). Thirty-eight (38) per cent of PCIS was suggested to be secondary to cardiac perforation. Specific symptoms or features include pleuritic chest pain (76.2%), fever (76.2%), elevated markers of inflammation (76.2%), pericardial effusion (90.5%), pleural effusion (71.4%) and pulmonary infiltrates (28.6%). Interestingly, all the six cases with pulmonary infiltrates were following AFL/AF ablation (6/15, 40%). Serious clinical manifestations include cardiac tamponade, massive pleural effusion with hypoalbuminaemia and hyponatraemia, and massive pulmonary infiltrates with hypoxaemia. Notably, empiric antibiotic therapy was used in seven cases including five with pulmonary infiltrates but failed to work. No mortality occurred during a mean follow-up of 4.1±5.3 (1 to 19) months.
CONCLUSIONS
Catheter ablation of AFL/AF was most commonly involved in ablation-associated PCIS. Pulmonary infiltrate is an important feature of PCIS following AFL/AF ablation and may be misdiagnosed as pneumonia. Although PCIS is troublesome and even dangerous, it does carry a benign prognosis.
Topics: Aged; Aged, 80 and over; Atrial Fibrillation; Catheter Ablation; Diagnosis, Differential; Diagnostic Errors; Heart Injuries; Humans; Male; Pericarditis; Radiography, Thoracic; Syndrome; Tomography, X-Ray Computed
PubMed: 30322760
DOI: 10.1016/j.hlc.2018.09.001 -
PLoS Neglected Tropical Diseases Jun 2018Chagas disease (CD) is a major public health concern in Latin America and a potentially serious emerging threat in non-endemic countries. Although the association... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Chagas disease (CD) is a major public health concern in Latin America and a potentially serious emerging threat in non-endemic countries. Although the association between CD and cardiac abnormalities is widely reported, study design diversity, sample size and quality challenge the information, calling for its update and synthesis, which would be very useful and relevant for physicians in non-endemic countries where health care implications of CD are real and neglected. We performed to systematically review and meta-analyze population-based studies that compared prevalence of overall and specific ECG abnormalities between CD and non-CD participants in the general population.
METHODS
Six databases (EMBASE, Ovid Medline, Web of Science, Cochrane Central, Google Scholar and Lilacs) were searched systematically. Observational studies were included. Odds ratios (OR) were computed using random-effects model.
RESULTS
Forty-nine studies were selected, including 34,023(12,276 CD and 21,747 non-CD). Prevalence of overall ECG abnormalities was higher in participants with CD (40.1%; 95%CIs=39.2-41.0) compared to non-CD (24.1%; 95%CIs=23.5-24.7) (OR=2.78; 95%CIs=2.37-3.26). Among specific ECG abnormalities, prevalence of complete right bundle branch block (RBBB) (OR=4.60; 95%CIs=2.97-7.11), left anterior fascicular block (LAFB) (OR=1.60; 95%CIs=1.21-2.13), combination of complete RBBB/LAFB (OR=3.34; 95%CIs=1.76-6.35), first-degree atrioventricular block (A-V B) (OR=1.71; 95%CIs=1.25-2.33), atrial fibrillation (AF) or flutter (OR=2.11; 95%CIs=1.40-3.19) and ventricular extrasystoles (VE) (OR=1.62; 95%CIs=1.14-2.30) was higher in CD compared to non-CD participants.
CONCLUSIONS
This systematic review and meta-analysis provides an update and synthesis in this field. This research of observational studies indicates a significant excess in prevalence of ECG abnormalities (40.1%) related to T. cruzi infection in the general population from Chagas endemic regions, being the most common ventricular (RBBB and LAFB), and A-V B (first-degree) node conduction abnormalities as well as arrhythmias (AF or flutter and VE). Also, prevalence of ECG alterations in children was similar to that in adults and suggests earlier onset of cardiac disease.
Topics: Adult; Arrhythmias, Cardiac; Chagas Cardiomyopathy; Chagas Disease; Child; Electrocardiography; Female; Heart Conduction System; Humans; Male; Observational Studies as Topic; Odds Ratio; Prevalence
PubMed: 29897909
DOI: 10.1371/journal.pntd.0006567 -
Heart, Lung & Circulation Aug 2015Atrial fibrillation (AF) often coexists with congestive cardiac failure (CCF), with multiple treatment options available. (Comparative Study)
Comparative Study Meta-Analysis Review
BACKGROUND
Atrial fibrillation (AF) often coexists with congestive cardiac failure (CCF), with multiple treatment options available.
METHODS
Systematic review and meta-analysis of randomised control trials (RCT) comparing pulmonary vein isolation (PVI), pharmacological rate control, and atrioventricular junction ablation with pacemaker insertion (AVJAP) for AF, with a subgroup analysis in patients with CCF. We analysed changes in left ventricular ejection fraction (LVEF), Minnesota Living with Heart Failure Questionnaire (MLHFQ) score, six-minute walk distance (6MWD), treadmill exercise time, and treatment complications. Results were expressed as weighted mean differences (WMD) with 95% Confidence-Intervals (95%CI).
RESULTS
We included seven RCT (425 participants). PVI was associated with a greater increase in LVEF (WMD+6.5%, 95%CI:+0.6to+12.5) and decrease in MLHFQ score (WMD-11.0, 95%CI:-2.6to-19.4) than pharmacological rate control in patients with CCF. PVI was also associated with a greater increase in LVEF (WMD+9.0%, 95%CI:+6.3to+11.7) and 6MWD (WMD+55.0metres, 95%CI:+34.9to+75.1), and decrease in MLHFQ score (WMD-22.0, 95%CI:-17.0to-27.0), compared to AVJAP in patients with CCF. Irrespective of cardiac function, pharmacological rate control had similar effects to AVJAP on LVEF (WMD+0.6%, 95%CI:-8.3to+9.4) and treadmill exercise time (WMD+0.5minutes, 95%CI:-0.4to+1.3).
CONCLUSIONS
Our results support the clinical implementation of PVI over AVJAP or pharmacological rate control in AF patients with CCF, who may or may not have already trialled pharmacological rhythm control.
Topics: Animals; Atrial Fibrillation; Heart Rate; Humans; Pulmonary Veins; Randomized Controlled Trials as Topic
PubMed: 25890871
DOI: 10.1016/j.hlc.2015.02.025