Assessment of resting myocardial blood flow in regions of known transmural scar to confirm accuracy and precision of 3D cardiac positron emission tomography.

BACKGROUND: Composite invasive and non-invasive data consistently demonstrate that resting myocardial blood flow (rMBF) in regions of known transmural myocardial scar (TMS) converge on a value of ~ 0.30 mL/min/g or lower. This value has been confirmed using the 3 most common myocardial perfusion agents (13N, 15O-H2O and 82Rb) incorporating various kinetic models on older 2D positron emission tomography (PET) systems. Thus, rMBF in regions of TMS can serve as a reference "truth" to evaluate low-end accuracy of various PET systems and software packages (SWPs). Using 82Rb on a contemporary 3D-PET-CT system, we sought to determine whether currently available SWP can accurately and precisely measure rMBF in regions of known TMS. RESULTS: Median rMBF (in mL/min/g) and COV in regions of TMS were 0.71 [IQR 0.52-1.02] and 0.16 with 4DM; 0.41 [0.34-0.54] and 0.10 with 4DM-FVD; 0.66 [0.51-0.85] and 0.11 with Cedars; 0.51 [0.43-0.61] and 0.08 with Emory-Votaw; 0.37 [0.30-0.42], 0.07 with Emory-Ottawa, and 0.26 [0.23-0.32], COV 0.07 with HeartSee. CONCLUSIONS: SWPs varied widely in low end accuracy based on measurement of rMBF in regions of known TMS. 3D PET using 82Rb and HeartSee software accurately (0.26 mL/min/g, consistent with established values) and precisely (COV = 0.07) quantified rMBF in regions of TMS. The Emory-Ottawa software yielded the next-best accuracy (0.37 mL/min/g), though rMBF was higher than established gold-standard values in ~ 5% of the resting scans. 4DM, 4DM-FDV, Cedars and Emory-Votaw SWP consistently resulted values higher than the established gold standard (0.71, 0.41, 0.66, 0.51 mL/min/g, respectively), with higher interscan variability (0.16, 0.11, 0.11, and 0.09, respectively). TRIAL REGISTRATION: clinicaltrial.gov, NCT05286593, Registered December 28, 2021, https://clinicaltrials.gov/ct2/show/NCT05286593 .

Impact of Preinfection Left Ventricular Ejection Fraction on Outcomes in COVID-19 Infection.

Coronavirus disease 2019 (COVID-19) has high infectivity and causes extensive morbidity and mortality. Cardiovascular disease is a risk factor for adverse outcomes in COVID-19, but baseline left ventricular ejection fraction (LVEF) in particular has not been evaluated thoroughly in this context. We analyzed patients in our state's largest health system who were diagnosed with COVID-19 between March 20 and May 15, 2020. Inclusion required an available echocardiogram within 1 year prior to diagnosis. The primary outcome was all-cause mortality. LVEF was analyzed both as a continuous variable and using a cutoff of 40%. Among 396 patients (67 ± 16 years, 191 [48%] male, 235 [59%] Black, 59 [15%] LVEF ≤40%), 289 (73%) required hospital admission, and 116 (29%) died during 85 ± 63 days of follow-up. Echocardiograms, performed a median of 57 (IQR 11-122) days prior to COVID-19 diagnosis, showed a similar distribution of LVEF between survivors and decedents (P = 0.84). Receiver operator characteristic analysis revealed no predictive ability of LVEF for mortality, and there was no difference in survival among those with LVEF ≤40% versus >40% (P = 0.49). Multivariable analysis did not change these relationships. Similarly, there was no difference in LVEF based on whether the patient required hospital admission (56 ± 13 vs 55 ± 13, P = 0.38), and patients with a depressed LVEF did not require admission more frequently than their preserved-LVEF peers (P = 0.87). A premorbid history of dyspnea consistent with symptomatic heart failure was not associated with mortality (P = 0.74). Among patients diagnosed with COVID-19, pre-COVID-19 LVEF was not a risk factor for death or hospitalization.

PET Stress Testing with Coronary Flow Capacity in the Evaluation of Patients with Coronary Artery Disease and Left Ventricular Dysfunction: Rethinking the Current Paradigm.

PURPOSE OF REVIEW: Cardiomyopathy with underlying left ventricular (LV) dysfunction is a heterogenous group of disorders that may be present with, and/or secondary to, coronary artery disease (CAD). The purpose of this review is to demonstrate, via case illustrations, the benefits offered by cardiac positron-emission tomography (PET) stress testing with coronary flow capacity (CFC) in the evaluation and treatment of patients with left ventricular (LV) dysfunction and CAD. RECENT FINDINGS: CFC, a metric that is increasing in prominence, represents the integration of several absolute perfusion metrics into clinical strata of CAD severity. Our prior work has demonstrated improvement in regional perfusion metrics as a result of revascularization to territories with severe reduction in CFC. Conversely, when CFC is adequate, there is no change in regional perfusion metrics following revascularization, despite angiographically severe stenosis. Furthermore, Gould et al. demonstrated decreased rates of myocardial infarction and death following revascularization of myocardium with severely reduced CFC, with no clinical benefit observed following revascularization of patients with preserved CFC. In a series of cases, we present pre-revascularization and post-revascularization PET scans with perfusion metrics in patients with LV dysfunction and CAD. In these examples, we demonstrate improvement in LV function and perfusion metrics following revascularization only in cases where baseline CFC is severely reduced. PET with CFC offers unique guidance regarding revascularization in patients with reduced LV function and CAD.

Positron emission tomography absolute stress myocardial blood flow for risk stratification in nonischemic cardiomyopathy.

INTRODUCTION: Sudden cardiac death is a substantial cause of mortality in patients with cardiomyopathy, but evidence supporting implantable cardioverter-defibrillator (ICD) implantation is less robust in nonischemic cardiomyopathy (NICM) than in ischemic cardiomyopathy. Improved risk stratification is needed. We assessed whether absolute quantification of stress myocardial blood flow (sMBF) measured by positron emission tomography (PET) predicts ventricular arrhythmias (VA) and/or death in patients with NICM. METHODS: In this pilot study, we prospectively followed patients with NICM (left ventricular ejection fraction ≤ 35%) and an ICD who underwent cardiac PET stress imaging with sMBF quantification. NICM was defined as the absence of angiographic obstructive coronary stenosis, significant relative perfusion defects on imaging, coronary revascularization, or acute coronary syndrome. Endpoints were appropriate device therapy for VA and all-cause mortality. Subgroup analysis was performed in patients who had no prior history of VA (ie, the primary prevention population). RESULTS: We followed 37 patients (60 ± 14 years, 46% male) for 41 ± 23 months. The median sMBF was 1.56 mL/g/min (interquartile range: 1.00-1.82). Lower sMBF predicted VA, both in the whole population (hazard ratio [HR] for each 0.1 mL/g/min increase: 0.84, P = .015) and in the primary prevention subset (n = 27; HR for each 0.1 mL/g/min increase: 0.81, P = .049). Patients with sMBF below the median had significantly more VA than those above the median, both in the whole population (P = .004) and in the primary prevention subset (P = .046). Estimated 3-year VA rates in the whole population were 67% among low-flow patients vs 13% among high-flow patients, and 39% vs 8%, respectively, among primary-prevention patients. sMBF did not predict all-cause mortality. CONCLUSIONS: In patients with NICM, lower sMBF predicts VA. This relationship may be useful for risk stratification for ventricular arrhythmia and decision making regarding ICD implantation.

Class 1C antiarrhythmic drugs in atrial fibrillation and coronary artery disease.

BACKGROUND: Class 1C antiarrhythmic drugs (AADs) are effective first-line agents for atrial fibrillation (AF) treatment. However, these agents commonly are avoided in patients with known coronary artery disease (CAD), due to known increased risk in the postmyocardial infarction population. Whether 1C AADs are safe in patients with CAD but without clinical ischemia or infarct is unknown. Reduced coronary flow capacity (CFC) on positron emission tomography (PET) reliably identifies myocardial regions supplied by vessels with CAD causing flow limitation. OBJECTIVE: To assess whether treatment with 1C AADs increases mortality in patients without known CAD but with CFC indicating significantly reduced coronary blood flow. METHODS: In this pilot study, we compared patients with AF and left ventricular ejection fraction ≥50% who were treated with 1C AADs to age-matched AF patients without 1C AAD treatment. No patient had clinically evident CAD (ie, reversible perfusion defect, known ≥70% epicardial lesion, percutaneous coronary intervention, coronary artery bypass grafting, or myocardial infarction). All patients had PET-based quantification of stress myocardial blood flow and CFC. Death was assessed by clinical follow-up and social security death index search. RESULTS: A total of 78 patients with 1C AAD exposure were matched to 78 controls. Over a mean follow-up of 2.0 years, the groups had similar survival (P = .54). Among patients with CFC indicating the presence of occult CAD (ie, reduced CFC involving ≥50% of myocardium), 1C-treated patients had survival similar to (P = .44) those not treated with 1C agents. CONCLUSIONS: In a limited population of AF patients with preserved left ventricle function and PET-CFC indicating occult CAD, treatment with 1C AADs appears not to increase mortality. A larger study would be required to confidently assess the safety of these drugs in this context.

Digital Management of Hypertension Improves Systolic Blood Pressure Variability.

BACKGROUND: Higher systolic blood pressure variability has been shown to be a better predictor of all-cause and cardiovascular disease mortality, stroke, and cardiac disease compared with average systolic blood pressure. METHODS: We evaluated the impact of a digital hypertension program on systolic blood pressure variability in 803 consecutive patients with long-standing hypertension who had been under the care of a primary care physician for a minimum of 12 months prior to enrollment (mean 4.7 years). Blood pressure readings were transmitted directly from home using a digitally connected blood pressure unit. Medication adjustments and lifestyle coaching was performed virtually via a dedicated team of pharmacists and health coaches. Systolic blood pressure variability was grouped by quartile and measured using the standard deviation (SD) of all systolic blood pressure values per individual. RESULTS: The mean age was 67 ± 12 years, 41% were male, submitting 3.3 ± 3.7 blood pressures per week. Under usual care, only 30% of patients were in the lowest-risk quartile, and 21% of patients were in the highest risk. After 24 months, the mean systolic blood pressure variability progressively fell from 12.8 ± 4.3 mm Hg to 9.9 ± 5.1 mm Hg (P <0.0001) with 57% of patients achieving the lowest-risk quartile. CONCLUSIONS: The majority of patients with hypertension under usual care have elevated systolic blood pressure variability exposing them to higher risk of cardiovascular disease events. Digital management of hypertension that includes weekly submission of home readings leads to improvement in average systolic blood pressure as well as systolic blood pressure variability over time, which should improve cardiovascular prognosis.

The impact of revascularization on myocardial blood flow as assessed by positron emission tomography.

PURPOSE: Revascularization aims to improve myocardial perfusion. However, changes in regional artery-specific quantitative perfusion after revascularization have not been systematically investigated. It is unclear whether artery-specific thresholds for coronary flow capacity (CFC) and/or relative perfusion predict improved stress perfusion after revascularization. We sought to determine the impact of revascularization based on predefined, artery-specific, severity size thresholds for CFC and/or relative perfusion defects. METHODS: Fifty patients underwent PET imaging before revascularization and then prospectively within 90 days after revascularization. Changes in regional myocardial blood flow (MBF) were stratified based on baseline perfusion abnormalities, baseline reduced CFC, and whether revascularization was performed in that region. RESULTS: Following angiographic stenosis-directed revascularization, in regions with relative perfusion abnormalities and decreased CFC, stress MBF (sMBF) increased by 0.51 cm3/min/g (59%) from baseline (p < 0.001). In regions without baseline perfusion abnormalities and yet decreased CFC, sMBF increased by 0.35 cm3/min/g (40%) from baseline (p < 0.001). In regions without perfusion abnormalities and normal CFC, sMBF did not increase significantly (+0.07 cm3/min/g, p = 0.56). Patients in whom revascularization was concordant with abnormal PET findings showed increased whole-heart sMBF (+0.22 cm3/min/g, p < 0.001), but in patients in whom revascularization was targeted only to regions without perfusion abnormalities or low CFC, sMBF did not change significantly (-0.06 cm3/min/g, p = 0.38). CONCLUSION: Revascularization targeted to regions with reduced CFC and relative perfusion abnormalities on baseline PET yielded significant improvements in sMBF. When revascularization was performed in regions without reduced CFC, sMBF did not improve.

Reducing Hospital Toxicity: Impact on Patient Outcomes.

BACKGROUND: Circadian rhythms are endogenous 24-hour oscillations in biologic processes that drive nearly all physiologic and behavioral functions. Disruption in circadian rhythms can adversely impact short- and long-term health outcomes. Routine hospital care often causes significant disruption in sleep-wake patterns that is further compounded by loss of personal control of health information and health decisions. We wished to evaluate measures directed at improving circadian rhythm and access to daily health information on hospital outcomes. METHODS: We evaluated 3425 consecutive patients admitted to a medical-surgical unit comprised of an intervention wing (n = 1185) or standard control wing (n = 2240) over a 2.5-year period. Intervention patients received measures to improve sleep that included reduction of nighttime noise, delay of routine morning phlebotomy, passive vital sign monitoring, and use of red-enriched lighting after sunset, as well as access to daily health information utilizing an inpatient portal. RESULTS: Intervention patients accessed the inpatient portal frequently during hospitalization seeking personal health and care team information. Measures impacting the quality and quantity of sleep were significantly improved. Length of stay was 8.6hours less (P = .04), 30- and 90-day readmission rates were 16% and 12% lower, respectively (both P ≤ .02), and self-rated emotional/mental health was higher (69.2% vs 52.4%; P = 0.03) in the intervention group compared with controls. CONCLUSIONS: Modest changes in routine hospital care can improve the hospital environment impacting sleep and access to health knowledge, leading to improvements in hospital outcomes. Sleep-wake patterns of hospitalized patients represent a potential avenue for further enhancing hospital quality and safety.

Hypertension management in the digital era.

PURPOSE OF REVIEW: Hypertension (HTN) is the most common chronic disease in the United States, and the standard model of office-based care delivery continues to yield suboptimal outcomes, with approximately 50% of affected patients not achieving blood pressure (BP) control. Poor population-level BP control has been primarily attributed to therapeutic inertia and low patient engagement resulting in significant and preventable morbidity and mortality. This review will highlight the rationale for a reengineered model of care delivery for populations with HTN. RECENT FINDINGS: New technologies now enable patients to generate accurate home-based BP readings that are transmitted directly into the electronic medical record. Using more frequent BP measurements in conjunction with assessment of social health determinants, computerized algorithms can be generated that provide tailored interventions and communications that can transform HTN control. SUMMARY: New capabilities enable healthcare providers the means to measure larger volumes of BP data directly from home and provide near real-time interventions that can dramatically improve HTN control.

The effect of coronary revascularization on regional myocardial blood flow as assessed by stress positron emission tomography.

OBJECTIVES: We examined whether regional improvement in stress myocardial blood flow (sMBF) following angiography-guided coronary revascularization depends on the existence of a perfusion defect on positron emission tomography (PET). BACKGROUND: Percent stenosis on coronary angiography often is the main factor when deciding whether to perform revascularization, but it does not reliably relate to maximum sMBF. PET is a validated method of assessing sMBF. METHODS: 19 patients (79% M, 65 ± 12 years) underwent PET stress before and after revascularization (17 PCI, 2 CABG). Pre- and post-revascularization sMBF for each left ventricular quadrant (anterior, septal, lateral, and inferior) was stratified by the presence or absence of a baseline perfusion defect on PET and whether that region was revascularized. RESULTS: Intervention was performed on 40 of 76 quadrants. When a baseline perfusion defect existed in a region that was revascularized (n = 26), post-revascularization flow increased by 0.6 ± 0.7 cc/min/g (1.2 ± 0.4 vs 1.7 ± 0.8, P < 0.001). When no defect existed but revascularization was performed (n = 14), sMBF did not change significantly (1.7 ± 0.3 vs 1.5 ± 0.4 cc/min/g, P = 0.16). In regions without a defect that were not revascularized (n = 29), sMBF did not significantly change (2.0 ± 0.6 vs 1.9 ± 0.7, P = 0.7). CONCLUSIONS: When a stress-induced perfusion defect exists on PET, revascularization improves sMBF in that region. When there is no such defect, sMBF shows no net change, whether or not intervention is performed in that area. PET stress may be useful for identifying areas of myocardium that could benefit from revascularization, and also areas in which intervention is unlikely to yield improvement in myocardial blood flow.

Improving Hypertension Control and Patient Engagement Using Digital Tools.

Hypertension is present in 30% of the adult US population and is a major contributor to cardiovascular disease. The established office-based approach yields only 50% blood pressure control rates and low levels of patient engagement. Available home technology now provides accurate, reliable data that can be transmitted directly to the electronic medical record. We evaluated blood pressure control in 156 patients with uncontrolled hypertension enrolled into a home-based digital-medicine blood pressure program and compared them with 400 patients (matched to age, sex, body mass index, and blood pressure) in a usual-care group after 90 days. Digital-medicine patients completed questionnaires online, were asked to submit at least one blood pressure reading/week, and received medication management and lifestyle recommendations via a clinical pharmacist and a health coach. Blood pressure units were commercially available that transmitted data directly to the electronic medical record. Digital-medicine patients averaged 4.2 blood pressure readings per week. At 90 days, 71% of digital-medicine vs 31% of usual-care patients had achieved target blood pressure control. Mean decrease in systolic/diastolic blood pressure was 14/5 mm Hg in digital medicine, vs 4/2 mm Hg in usual care (P < .001). Excess sodium consumption decreased from 32% to 8% in the digital-medicine group (P = .004). Mean patient activation increased from 41.9 to 44.1 (P = .008), and the percentage of patients with low patient activation decreased from 15% to 6% (P = .03) in the digital-medicine group. A digital hypertension program is feasible and associated with significant improvement in blood pressure control rates and lifestyle change. Utilization of a virtual health intervention using connected devices improves patient activation and is well accepted by patients.

New Concepts in Hypertension Management: A Population-Based Perspective.

Hypertension (HTN) is the most common chronic disease in the U.S., and the standard model of office-based care delivery has yielded suboptimal outcomes, with approximately 50% of affected patients not achieving blood pressure (BP) control. Poor population-level BP control has been primarily attributed to therapeutic inertia and low patient engagement. New models of care delivery utilizing patient-generated health data, comprehensive assessment of social health determinants, computerized algorithms generating tailored interventions, frequent communication and reporting, and non-physician providers organized as an integrated practice unit, have the potential to transform population-based HTN control. This review will highlight the importance of these elements and construct the rationale for a reengineered model of care delivery for populations with HTN.

The Role of Technology in Chronic Disease Care.

Chronic disease represents the epidemic of our time, present in half the adult population and responsible for 86% of United States (US) healthcare costs and 70% of deaths. The major chronic diseases are primarily due to health risk behaviors that are widely communicable across populations. As a nation, the US has performed poorly in managing chronic disease, in large part because of a failed delivery model of care. New opportunities exist as a result of recent advances in home-based wireless devices, apps and wearables, enabling health delivery systems to monitor disease metrics in near real time. These technologies provide a framework for patient engagement and a new model of care delivery utilizing integrated practice units, both of which are needed to navigate the healthcare needs of the 21st century.

What is ischemia and how should this be defined based on modern imaging?

How do we define myocardial ischemia? This is an important question for clinicians and one that, while conceptually straight forward, can be practically difficult to assess. In this article we describe the various imaging methods available in cardiology to quantify myocardial ischemia. Anatomic assessments of ischemia such as angiography, while the "gold standard", have limitations. While some of these limitations can be mitigated with invasively measurements of fractional flow reserve or intravascular ultrasound, these tools have their own weaknesses. Non-invasive metabolic assessment, such as measuring glucose and fatty acid metabolism, are reliable in identifying ischemic, hibernating, or stunned myocardium but can be difficult to use clinically. Non-invasive physiologic assessment with myocardial perfusion agents with single photon emission tomography imaging and positron emission tomography (PET) with measurement of absolute myocardial flow additionally have their own strengths and weaknesses. In this article we review the data behind the various cardiac modalities used in defining myocardial assessments along with their strengths, practical use, and limitations. We conclude by discussing an integrative approach of relative uptake and absolute myocardial flow using cardiac PET imaging that allows for a more accurate assessment of ischemia along with cases demonstrating various scenarios available in cardiac PET imaging.