Phase analysis of gated blood pool SPECT for multiple stress testing assessments of ventricular mechanical dyssynchrony in a tachycardia-induced dilated cardiomyopathy canine model.

BACKGROUND: Stress-induced dyssynchrony has been shown to be independently correlated with clinical outcomes in patients with dilated cardiomyopathy (DCM) and narrow QRS complexes. However, the extent to which stress levels affect inter- and intraventricular dyssynchrony parameters remains unknown. METHODS: Ten large dogs were submitted to tachycardia-induced DCM by pacing the right ventricular apex for 3-4 weeks to reach a target ejection fraction (EF) of 35% or less. Stress was then induced in DCM dogs by administering intravenous dobutamine up to a maximum of 20 µg·kg-1·min-1. Hemodynamic and ventricular dyssynchrony data were analyzed by left ventricular (LV) pressure measurements and gated blood pool SPECT (GBPS) imaging. In order to assess mechanical dyssynchrony in DCM subjects and compare it with that of 8 normal counterparts, we extracted the following data: count-based indices of LV contraction homogeneity index (CHI), entropy and phase standard deviation, and interventricular dyssynchrony index. RESULTS: A significant LV intraventricular dyssynchrony (CHI: 96.4 ± 1.3% in control vs 78.6% ± 10.9% in DCM subjects) resulted in an intense LV dysfunction in DCM subjects (EF: 49.5% ± 8.4% in control vs 22.6% ± 6.0% in DCM), compared to control subjects. However, interventricular dyssynchrony did not vary significantly between the two groups. Under stress, DCM subjects showed a significant improvement in ventricular functional parameters at each level (EF: 22.6% ± 6.0% at rest vs 48.1% ± 5.8% at maximum stress). All intraventricular dyssynchrony indices showed a significant increase in magnitude of synchrony from baseline to stress levels of greater than or equal to 5 µg·kg-1·min-1 dobutamine. There were individual differences in the magnitude and pattern of change in interventricular dyssynchrony during the various levels of stress. CONCLUSIONS: Based on GBPS analyses, different levels of functional stress, even in close intervals, can have a significant impact on hemodynamic and intraventricular dyssynchrony parameters in a DCM model with narrow QRS complex.

Electrochemical DNA biosensor based on gold nanorods for detecting hepatitis B virus.

The purpose of this work was to fabricate an electrochemical DNA biosensor for detecting hepatitis B virus. Gold nanorods (GNRs), which are known for their conductivity, were used to increase surface area and consequently increase the immobilization of single-stranded DNA (ss-DNA) on the modified gold electrode. The GNRs were characterized via transmission electron microscopy. The morphology of the gold electrode before and after modification with GNRs was characterized by scanning electron microscopy. Atomic-force microscopy was used to evaluate the morphology of the GNR electrode surface before and after interaction with ss-DNA. Cyclic voltammetry was used to monitor DNA immobilization and hybridization, using [Co(phen)3](3+) as an electrochemical indicator. The target DNA sequences were quantified at a linear range from 1.0 × 10(-12) to 10.0 × 10(-6) mol L(-1), with a detection limit of 2.0 × 10(-12) mol L(-1) by 3σ. The biosensor had good specificity for distinguishing complementary DNA in the presence of non-complementary and mismatched DNA sequences.

The effects of dobutamine stress on cardiac mechanical synchrony determined by phase analysis of gated SPECT myocardial perfusion imaging in a canine model.

BACKGROUND: Precise identification of left ventricular (LV) systolic mechanical dyssynchrony may be useful in optimizing the response to cardiac resynchronization therapy in heart failure (HF) patients. However, LV dyssynchrony is mostly measured at rest; patients often suffer from the HF symptoms during exercise. OBJECTIVES: Our objective was to examine the impacts of stress on LV synchronism with phase analysis of gated SPECT myocardial perfusion imaging (GMPS) within a normal animal cohort. METHODS: Stress was induced with different levels of dobutamine infusion in six healthy canine subjects. Hemodynamic properties were assessed by LV pressure measurements. Also, LV mechanical synchronism (coordination of LV septal and lateral wall at the time of contraction) was determined by phase analysis of GMPS using commercially available QGS software and in-house MHI4MPI software, with the thickening- and displacement-based method. Synchrony indexes in MHI4MPI included the septal-to-lateral delay and homogeneity index, derived from each of the two methods. Also, bandwidth, SD, and entropy (synchrony indexes) of the QGS software were assessed. RESULTS: LVEF increased from 36.7% ± 8.7% at rest to 53.67% ± 12.34% at 20 µg · kg(-1) · minute(-1) (P < .001). Also, cardiac output increased from 3.67 ± 1.0 L · minute(-1) at rest to 8.4 ± 2.6 L · minute(-1) at 10 µg · kg(-1) · minute(-1) (P < .001). The same trend was observed for dP/dt max which increased from 1,247 ± 382.7 at rest to 5,062 ± 1,800 mm Hg · s(-1) at 10 µg · kg(-1) · minute(-1) (P < .01). Entropy decreased from 55.2% ± 8% at baseline to 43.5% ± 8.5% at 5 and 43.0% ± 3.7% at 10 µg · kg(-1) · minute(-1) dobutamine (P < .01). Thickening homogeneity index showed a difference from 91.7% ± 5.53% at rest to 98.2% ± 0.75% at 20 µg · kg(-1) · minute(-1) (P < .05). CONCLUSIONS: Dobutamine stimulation could amplify the ventricular synchronism, and the thickening-based approach is more accurate than wall displacement for assessment of mechanical dyssynchrony in GMPS.

Impact of the method of calculating 30-day readmission rate after hospitalization for heart failure. Data from the VancOuver CoastAL Acute Heart Failure (VOCAL-AHF) registry.

BACKGROUND: Thirty-day readmission rate after heart failure (HF) hospitalization is widely used to evaluate healthcare quality. Methodology may substantially influence estimated rates. We assessed the impact of different definitions on HF and all-cause readmission rates. METHODS: Readmission rates were examined in 1835 patients discharged following HF hospitalization using 64 unique definitions derived from five methodological factors: (1) International Classification of Diseases-10 codes (broad vs. narrow), (2) index admission selection (single admission only first-in-year vs. random sample; or multiple admissions in year with vs. without 30-day blanking period), (3) variable denominator (number alive at discharge vs. number alive at 30 days), (4) follow-up period start (discharge date vs. day following discharge), and (5) annual reference period (calendar vs. fiscal). The impact of different factors was assessed using linear regression. RESULTS: The calculated 30-day readmission rate for HF varied more than two-fold depending solely on the methodological approach (6.5-15.0%). All-cause admission rates exhibited similar variation (18.8-29.9%). The highest rates included all consecutive index admissions (HF 11.1-15.0%, all-cause 24.0-29.9%), and the lowest only one index admission per patient per year (HF 6.5-11.3%, all-cause 18.8-22.7%). When including multiple index admissions and compared with blanking the 30-day post-discharge, not blanking was associated with 2.3% higher readmission rates. Selecting a single admission per year with a first-in-year approach lowered readmission rates by 1.5%, while random-sampling admissions lowered estimates further by 5.2% (P < 0.001). CONCLUSION: Calculated 30-day readmission rates varied more than two-fold by altering methods. Transparent and consistent methods are needed to ensure reproducible and comparable reporting.

Epidemiology and treatment of heart failure with chronic obstructive pulmonary disease in Canadian primary care.

AIMS: Heart failure (HF) and chronic obstructive pulmonary disease (COPD) are largely managed in primary care, but their intersection in terms of disease burden, healthcare utilization, and treatment is ill-defined. METHODS AND RESULTS: We examined a retrospective cohort including all patients with HF or COPD in the Canadian Primary Care Sentinel Surveillance Network from 2010 to 2018. The population size in 2018 with HF, COPD, and HF with COPD was 15 778, 27 927, and 4768 patients, respectively. While disease incidence declined, age-sex-standardized prevalence per 100 population increased for HF alone from 2.33 to 3.63, COPD alone from 3.44 to 5.96, and COPD with HF from 12.70 to 15.67. Annual visit rates were high and stable around 8 for COPD alone but declined significantly over time for HF alone (9.3-8.1, P = 0.04) or for patients with both conditions (14.3-11.9, P = 0.006). For HF alone, cardiovascular visits were common (29.4%), while respiratory visits were infrequent (3.5%), with the majority of visits being non-cardiorespiratory. For COPD alone, respiratory and cardiovascular visits were common (16.4% and 11.3%) and the majority were again non-cardiorespiratory. For concurrent disease, 39.0% of visits were cardiorespiratory. The commonest non-cardiorespiratory visit reasons were non-specific symptoms or signs, endocrine, musculoskeletal, and mental health. In patients with HF with and without COPD, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker/angiotensin receptor-neprilysin inhibitor use was similar, while mineralocorticoid receptor antagonist use was marginally higher with concurrent COPD. Beta-blocker use was initially lower with concurrent COPD compared with HF alone (69.3% vs. 74.0%), but this progressively declined by 2018 (74.5% vs. 73.5%). CONCLUSIONS: The prevalence of HF and COPD continues to rise. Although patients with either or both conditions are high utilizers of primary care, the majority of visits relate to non-cardiorespiratory comorbidities. Medical therapy for HF was similar and the initially lower beta-blocker utilization disappeared over time.

Defining the gap in heart failure treatment in patients with cardiac implantable electronic devices.

BACKGROUND: The use of guideline-directed medical therapy (GDMT) is poorly described in patients with heart failure and reduced ejection fraction (HFrEF) with cardiac resynchronization therapy (CRT) and/or implantable cardioverter defibrillators (ICDs). OBJECTIVE: To define the eligibility, uptake, dose, contraindications, and barriers to uptake of contemporary medical therapy in this population. METHODS: Retrospective analysis of consecutive adults with ICD and/or CRT attending two Canadian tertiary centre device clinics between 1 March and 31 May 2021. RESULTS: From 1005 device clinic consultations, 227 (22.6%) patients with HFrEF and CRT and/or ICD were included. GDMT eligibility was high: beta-blockers (99.6%), mineralocorticoid receptor antagonists (MRA) (89.0%), angiotensin receptor-neprilysin inhibitors (ARNI) (84.6%), and sodium-glucose cotransporter-2 inhibitors (SGLT2I) (87.7%). Contraindications were rare: beta-blockers (0.4%), MRA (11.0%), ARNI (15.4%), and SGLT2I (12.3%). Uptake of GDMT was high for beta-blockers (97.4%) but low for other medications: MRA (63.0%), ARNI (46.7%), SGLT2I (22.9%). Except for SGLT2I (84.6%) and beta-blockers (57.9%), less than one-half of patients were prescribed target-doses of MRA (10.5%), and ARNI (47.7%). Of the visits, GDMT was already optimal in 16%, electrophysiologists acted in 33% (21% prescribed, 7% ordered investigations, 5% referred to heart function services), and in the remaining visits, optimization was either deferred to another cardiologist (20%) or no plan was mentioned (25%), besides other reasons (4%). CONCLUSION: Despite broad eligibility for GDMT in patients with HFrEF and ICD/CRT, significant gaps in prescription and titration exist. Our results highlight the need to embed quality assurance initiatives in cardiac device clinics to improve HFrEF care.

Heart failure treatment in patients with cardiac implantable electronic devices: Opportunity for improvement.

BACKGROUND: Heart failure and reduced ejection fraction (HFrEF) is the predominant indication for cardiac resynchronization therapy (CRT) and implantable cardioverter-defibrillator (ICD) implantation. The care gap and opportunity to optimize guideline-directed medical therapy (GDMT) is unclear. OBJECTIVE: We sought to define uptake, eligibility, dose, and adherence to GDMT in patients with CRT/ICD and HFrEF. METHODS: MEDLINE was searched from 2000 to July 2021 for major randomized trials, registries, and cohort studies evaluating GDMT in this population. Thirty-eight studies focused on medical therapy in patients with CRT/ICD devices (CRT = 23, ICD = 11, and both = 4). RESULTS: In the pivotal device trials, ACEI/ARB and beta-blocker use was high (mean 94%, range 41%-99%; and 83%, range 27%-97%, respectively), but mineralocorticoid receptor antagonists were modest (mean 45%, range 32%-61%), in keeping with guidelines of that era. Similar results were found in observational registries. CRT was associated with beta-blocker uptitration, while the effects on ACEI/ARB were less consistent. For beta blockers, 57%-68% of patients were uptitrated, increasing the mean percent of target dose achieved by 24% from baseline to follow-up. In one study, adherence increased, for ACEI/ARB from 37% to 55% and beta blockers 34% to 58%. Only 1 study assessed potential eligibility at implant for sacubitril-valsartan (72%) or ivabradine (28%), and no study examined sodium-glucose cotransporter-2 inhibitors. Increased uptake, titration, and dose was associated with reduced mortality, hospitalization, and device therapies. CONCLUSION: Patients with HFrEF and ICD/CRT are undertreated with respect to GDMT, and there is opportunity to optimize therapy to improve morbidity and mortality.

Effects of dobutamine stress on cardiac contraction synchronism in a canine model.

In cardiac resynchronization therapy, many devices need to be optimized to take into account the magnitude and characteristics of patients' ventricular mechanical dyssynchrony. The optimization process is mostly performed at rest; however, mechanical resynchronization might be more important under stress, while patients need to improve their cardiac efficiency. The objective of this study was to observe if levels of cardiac stress could modify the ventricular contraction synchronism. Cardiac stress was induced with dobutamine infusion in eight healthy canine subjects. Hemodynamic and ventricular synchronism assessments were performed by left ventricular pressure measurements and radionuclide tomographic-gated blood pools. Cardiac output increased from 2.8 ± 1.0 at rest to 5.7 ± 2.2 L min(-1) at 20 µg kg(-1) min(-1), while the ventricular performance (dP/dtmax) increased from 1588 ± 374 to 8004 ± 710 mmHg s(-1). At baseline, the interventricular delay (in degrees) was -6.3 ± 2.6°, the left ventricle contraction preceding the right. The delay significantly increased to -21.6 ± 3.1° with dobutamine stress (p < 0.0001). On assessment of the left intraventricular synchrony, septal-to-lateral delay was -6.9 ± 5.1° at baseline which revealed a preceded contraction of the left lateral wall from the septum. Cardiac stress produced a significant modulation (p = 0.01), with an inversion of the contraction pattern, the septum contraction preceding the lateral wall contraction by 15.5 ± 5.6° at maximum dobutamine infusion; a significant linear trend (p < 0.001) was found between cardiac stress levels and septal-to-lateral delays. Cardiac activity levels modified the ventricular synchronism supporting the fact that optimizations of cardiac resynchronization devices could be improved by taking cardiac stress into account.