PET myocardial perfusion quantification: anatomy of a spreading functional technique

Purpose To summarize the physical principles, imaging method, available tools for and the clinical value of quantitative perfusion evaluation with cardiac PET as well as future aims in the field in a narrative review.Results Cardiac positron-emission tomography (PET) currently constitutes the reference standard for non-invasive quantitative evaluation of myocardial blood flow. This added modality provides useful information beyond standard semi-quantitative myocardial perfusion evaluation. A description of how the different phases of PET studies are interpreted is provided, as well as a short depiction of the most commonly used radiotracers and the main characteristics affecting their clinical utility. The diagnostic and prognostic utility concerning myocardial perfusion quantified in absolute terms is discussed and the additional contribution of the increasingly spread hybrid equipment is summarized.Conclusion PET myocardial perfusion represents an excellent noninvasive technique for the evaluation of known or suspected ischemic heart disease, and its clinical application should widen in the near future. The clinical value of PET quantitative perfusion is expected to improve patient outcomes and optimize therapeutic decisions, which constitute key elements for the future of cardiovascular medicine

Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to 300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m 2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to &lt;90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], &gt;300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of &lt;15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P&lt;0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P&lt;0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Effect of SGLT2 inhibitors on stroke and atrial fibrillation in diabetic kidney disease: Results from the CREDENCE trial and meta-analysis

BACKGROUND AND PURPOSE: Chronic kidney disease with reduced estimated glomerular filtration rate or elevated albuminuria increases risk for ischemic and hemorrhagic stroke. This study assessed the effects of sodium glucose cotransporter 2 inhibitors (SGLT2i) on stroke and atrial fibrillation/flutter (AF/AFL) from CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation) and a meta-Analysis of large cardiovascular outcome trials (CVOTs) of SGLT2i in type 2 diabetes mellitus. METHODS: CREDENCE randomized 4401 participants with type 2 diabetes mellitus and chronic kidney disease to canagliflozin or placebo. Post hoc, we estimated effects on fatal or nonfatal stroke, stroke subtypes, and intermediate markers of stroke risk including AF/AFL. Stroke and AF/AFL data from 3 other completed large CVOTs and CREDENCE were pooled using random-effects meta-Analysis. RESULTS: In CREDENCE, 142 participants experienced a stroke during follow-up (10.9/1000 patient-years with canagliflozin, 14.2/1000 patient-years with placebo; hazard ratio [HR], 0.77 [95% CI, 0.55-1.08]). Effects by stroke subtypes were: ischemic (HR, 0.88 [95% CI, 0.61-1.28]; n=111), hemorrhagic (HR, 0.50 [95% CI, 0.19-1.32]; n=18), and undetermined (HR, 0.54 [95% CI, 0.20-1.46]; n=17). There was no clear effect on AF/AFL (HR, 0.76 [95% CI, 0.53-1.10]; n=115). The overall effects in the 4 CVOTs combined were: Total stroke (HRpooled, 0.96 [95% CI, 0.82-1.12]), ischemic stroke (HRpooled, 1.01 [95% CI, 0.89-1.14]), hemorrhagic stroke (HRpooled, 0.50 [95% CI, 0.30-0.83]), undetermined stroke (HRpooled, 0.86 [95% CI, 0.49-1.51]), and AF/AFL (HRpooled, 0.81 [95% CI, 0.71-0.93]). There was evidence that SGLT2i effects on total stroke varied by baseline estimated glomerular filtration rate (P=0.01), with protection in the lowest estimated glomerular filtration rate (45 mL/min/1.73 m2]) subgroup (HRpooled, 0.50 [95% CI, 0.31-0.79]). CONCLUSIONS: Although we found no clear effect of SGLT2i on total stroke in CREDENCE or across trials combined, there was some evidence of benefit in preventing hemorrhagic stroke and AF/AFL, as well as total stroke for those with lowest estimated glomerular filtration rate. Future research should focus on confirming these data and exploring potential mechanisms

The performance of non-invasive tests to rule-in and rule-out significant coronary artery stenosis in patients with stable angina: a meta-analysis focused on post-test disease probability

Aims: To determine the ranges of pre-test probability (PTP) of coronary artery disease (CAD) in which stress electrocardiogram (ECG), stress echocardiography, coronary computed tomography angiography (CCTA), single-photon emission computed tomography (SPECT), positron emission tomography (PET), and cardiac magnetic resonance (CMR) can reclassify patients into a post-test probability that defines (>85%) or excludes (<15%) anatomically (defined by visual evaluation of invasive coronary angiography [ICA]) and functionally (defined by a fractional flow reserve [FFR] ≤0.8) significant CAD. Methods and results: A broad search in electronic databases until August 2017 was performed. Studies on the aforementioned techniques in >100 patients with stable CAD that utilized either ICA or ICA with FFR measurement as reference, were included. Study-level data was pooled using a hierarchical bivariate random-effects model and likelihood ratios were obtained for each technique. The PTP ranges for each technique to rule-in or rule-out significant CAD were defined. A total of 28 664 patients from 132 studies that used ICA as reference and 4131 from 23 studies using FFR, were analysed. Stress ECG can rule-in and rule-out anatomically significant CAD only when PTP is ≥80% (76-83) and ≤19% (15-25), respectively. Coronary computed tomography angiography is able to rule-in anatomic CAD at a PTP ≥58% (45-70) and rule-out at a PTP ≤80% (65-94). The corresponding PTP values for functionally significant CAD were ≥75% (67-83) and ≤57% (40-72) for CCTA, and ≥71% (59-81) and ≤27 (24-31) for ICA, demonstrating poorer performance of anatomic imaging against FFR. In contrast, functional imaging techniques (PET, stress CMR, and SPECT) are able to rule-in functionally significant CAD when PTP is ≥46-59% and rule-out when PTP is ≤34-57%. Conclusion: The various diagnostic modalities have different optimal performance ranges for the detection of anatomically and functionally significant CAD. Stress ECG appears to have very limited diagnostic power. The selection of a diagnostic technique for any given patient to rule-in or rule-out CAD should be based on the optimal PTP range for each test and on the assumed reference standard

Is It Possible to Predict Cardiac Death?

Cardiovascular diseases are the leading cause of death in all the world; despite having the knowledge of the main risk factors, they keep on being complicated pathologies to deal with. Cardiovascular management has introduced a lot of parameters as regards patients’ state of health; particularly, nuclear cardiology with Stress single-photon emission computed tomography myocardial perfusion imaging can carry out interesting parameters that have encouraged researchers to apply machine learning techniques to predict whether patients will die due to a cardiac event or not. The dataset consisted of 661 patients that were evaluated for suspected of known coronary artery disease at the Department of Advanced Biomedical Sciences of the University Hospital “Federico II” in Naples. Knime analytics platform was employed to implement a decision tree and Random forests. After a procedure of features reduction, 29 features were included, and the overall accuracy was 91.0%, while recall, precision, sensitivity and specificity overcame the value of 90.0%. This implementation shows the feasibility of machine learning combined with data coming from nuclear cardiology. Moreover, the possibility to predict cardiac death exploiting clinical data and parameters carried out from instrumental exams would help clinicians to provide patients with the best treatments and interventions