A case of disappearing amyloid on technetium pyrophosphate scan.

Technetium-99mm pyrophosphate (Tc-PYP) scintigraphy is a highly accurate non-invasive method for the diagnosis of transthyretin (ATTR) cardiac amyloidosis. Prognosis for this disease is improved following treatment with the transthyretin (TTR) stabilizer tafamidis. Although tafamidis slows disease progression, its effects on myocardial amyloid and Tc-PYP uptake remain unclear. We present a patient with ATTR cardiac amyloidosis who had a strongly positive initial Tc-PYP scan, with a dramatic decrease in Tc-PYP uptake on repeat scan after 3 years of tafamidis treatment. However, myocardial biopsy showed persistent diffuse amyloid deposits. This case highlights the need for further studies regarding the utility of serial Tc-PYP scans in monitoring the progress of ATTR cardiomyopathy.

Impact of chronic obstructive pulmonary disease on heart failure hospitalizations after an acute myocardial infarction.

Introduction: The presence of chronic obstructive pulmonary disease (COPD) can impact the management of acute myocardial infarction (AMI) and is associated with higher mortality. Few studies addressed COPD impact on heart failure hospitalisations (HFHs) in AMI survivors. Material and methods: Adult survivors of an AMI between January and June 2014 were identified from the US Nationwide Readmissions Database. The impact of COPD on HFH within 6 months, fatal HFH and the composite of in-hospital HF or 6-month HFH was studied. Results: Of 237,549 AMI survivors, patients with COPD (17.5%) were older, more likely female, had a higher prevalence of cardiac comorbidities and a lower coronary revascularization rate. In-hospital HF was more frequent in patients with COPD (47.0% vs. 25.4%; p < 0.001). HFH within 6 months occured in 12,934 (5.4%) patients, at a 114% higher rate in patients with COPD (9.4% vs. 4.6%, OR = 2.14, 95% CI : 2.01-2.29; p < 0.001), which was attenuated to a 39% higher adjusted risk (OR = 1.39, 95% CI: 1.30-1.49). Findings were consistent across subgroups of age, AMI type, and major HF risk factors. Mortality during a HFH (5.7% vs. 4.2%, p < 0.001) and the rate of the composite HF outcome (49.0% vs. 26.9%, p < 0.001) were significantly higher in patients with COPD. Conclusions: COPD was present in 1 of 6 AMI survivors and was associated with worse HF related outcomes. The increased HFH rate in COPD patients was consistent across several clinically relevant subgroups and these findings highlight the need for optimal in-hospital and post-discharge management of these higher-risk patients.

The Emerging Role of FDG PET/CT in Diagnosing Endocarditis and Cardiac Device Infection.

Infective endocarditis and cardiac implantable electronic device infection (CIEDI) have witnessed an increasing incidence in clinical practice and associated with increasing health care expenditure. Expanding indications of CIED in various cardiovascular conditions have also contributed to the surge of these infections. Early diagnosis of these infections is associated with a favorable prognosis. Given the lack of a single definitive diagnostic method and the limitations of echocardiography, which is considered a central diagnostic imaging modality, additional imaging modalities are required. Recent studies have highlighted the diagnostic utility of FDG PET and CT. In this review article, we discuss the existing limitations of echocardiography, acquisition protocols of PET/CT, and indications of these advanced imaging modalities in infective endocarditis and CIEDI diagnosis.

Positron Emission Tomography (PET) with 18F-FGA for Diagnosis of Myocardial Infarction in a Coronary Artery Ligation Model.

Location and extent of necrosis are valuable information in the management of myocardial infarction (MI). Methods. We investigated 2-deoxy-2-18F-fluoro glucaric acid (FGA), a novel infarct-avid agent, for positron emission tomography (PET) of MI. We synthesized FGA from commercially available 18F-fluoro-2-deoxy-2-D-glucose (FDG). MI was induced in mice by permanently occluding the left anterior descending coronary artery. Biodistribution of FGA was assessed 1 h after FGA injection (11 MBq). PET/CT was conducted 1 h, 6 h, 1 d, 3 d, and 4 d after MI. Subcellular compartment of FGA accumulation in necrosis was studied by tracing the uptake of biotin-labeled glucaric acid with streptavidin-HRP in H2O2-treated H9c2 cardiomyoblasts. Streptavidin-reactive protein bands were identified by LC-MS/MS. Results. We obtained a quantitative yield of FGA from FDG within 7 min (radiochemical purity > 99%). Cardiac uptake of FGA was significantly higher in MI mice than that in control mice. Imaging after 1 h of FGA injection delineated MI for 3 days after MI induction, with negligible background signal from surrounding tissues. Myocardial injury was verified by tetrazolium staining and plasma troponin (47.63 pg/mL control versus 311.77 pg/mL MI). In necrotic H9c2 myoblasts, biotinylated glucaric acid accumulated in nuclear fraction. LC-MS/MS primarily identified fibronectin in necrotic cells as a putative high fidelity target of glucaric acid. Conclusion. FGA/PET detects infarct early after onset of MI and FGA accumulation in infarct persists for 3 days. Its retention in necrotic cells appears to be a result of interaction with fibronectin that is known to accumulate in injured cardiac tissue.

A simplified wall-based model for regional innervation/perfusion mismatch assessed by cardiac 123I-mIBG and rest 99mTc-tetrofosmin SPECT to predict arrhythmic events in ischaemic heart failure.

AIMS: Cardiac 123iodine-meta-iodobenzylguanidine (123I-mIBG) single-photon emission computed tomography (SPECT) imaging provides information on regional myocardial innervation. However, the value of the commonly used 17-segment summed defect score (SDS) as a prognostic marker is uncertain. The present study examined whether a simpler regional scoring approach for evaluation of 123I-mIBG SPECT combined with rest 99mTc-tetrofosmin SPECT myocardial perfusion imaging could improve prediction of arrhythmic events (AEs) in patients with ischaemic heart failure (HF). METHODS AND RESULTS: Five hundred and two ischaemic HF subjects of the ADMIRE-HF study with complete cardiac 123I-mIBG and rest 99mTc-tetrofosmin SPECT studies were included. Both SPECT image sets were read together by two experienced nuclear imagers and scored by consensus. In addition to standard 17-segment scoring, the readers classified walls (i.e. anterior, lateral, inferior, septum and apex) as normal, matched defect, mismatched (innervation defect > perfusion defect), or reverse mismatched (perfusion defect > innervation defect). Cox proportional hazards ratios (HRs) were used to determine if age, body mass index, functional class, left ventricular ejection fraction (LVEF), B-type natriuretic peptide (BNP), norepinephrine, 123I-mIBG SDS, 99mTc-tetrofosmin SDS, innervation/perfusion mismatch SDS, and our simplified visual innervation/perfusion wall classification were associated with occurrence of AEs (i.e. sudden cardiac death, sustained ventricular tachycardia, resuscitated cardiac arrest, appropriate implantable cardioverter-defibrillator therapy). At 2-year median follow-up, 52 subjects (10.4%) had AEs. Subjects with 1 or 2 mismatched walls were twice as likely to have AEs compared with subjects with either 0 or 3-5 mismatched walls (16.3% vs. 8.3%, P = 0.010). Cox regression analyses showed that patients with a visual mismatch in 1-2 walls had an almost two times higher risk of AEs [HR 2.084 (1.109-3.914), P = 0.001]. None of the other innervation, perfusion and mismatch scores using standard 17 segments were associated with AEs. BNP (ng/L) was the only non-imaging parameter associated with AEs. CONCLUSION: A visual left ventricular wall-level based scoring method identified highest AE risk in ischaemic HF subjects with intermediate levels of innervation/perfusion mismatches. This simple technique for the evaluation of SPECT studies, which are often challenging in HF subjects, seems to be superior to the 17-segment scoring method.

Influence of diabetes mellitus interactions with cardiovascular risk factors on post-myocardial infarction heart failure hospitalizations.

OBJECTIVE: There is a paucity of information regarding how cardiovascular risk factors (RF) modulate the impact of diabetes mellitus (DM) on the heart failure hospitalization (HFH) risk following an acute myocardial infarction (AMI). METHODS: Adult survivors of an AMI were retrospectively identified from the 2014 US Nationwide Readmissions Database. The impact of DM on the risk for a 6-month HFH was studied in subgroups of RFs using multivariable logistic regression to adjust for baseline risk differences. Individual interactions of DM with RFs were tested. RESULTS: Of 237,549 AMI survivors, 37.2% patients had DM. Primary outcome occurred in 12,934 patients (5.4%), at a 106% higher rate in DM patients (7.9% vs 4.0%, p < 0.001), which was attenuated to a 45% higher adjusted risk. Higher HFH risk in DM patients was consistent across subgroups and significant interactions were present between DM and other RFs. The increased HFH risk with DM was more pronounced in patients without certain HF RFs compared with those with these RFs [age < 65: OR for DM 1.84 (1.58-2.13) vs age ≥ 65: OR 1.34 (1.24-1.45); HF absent during index AMI: OR for DM 1.87 (1.66-2.10) vs HF present: OR 1.24 (1.14-1.34); atrial fibrillation absent: OR for DM 1.57 (1.46-1.68) vs present: OR 1.19 (1.06-1.33); Pinteraction < 0.001 for all]. Similar results were noted for hypertension and chronic kidney disease. CONCLUSIONS: AMI survivors with DM had a higher risk of 6-month HFHs. The impact of DM on the increased HFH risk was more pronounced in patients without certain RFs suggesting that more aggressive preventive strategies related to DM and HF are needed in these subgroups to prevent or delay the onset of HFHs.

Nuclear Imaging for the Assessment of Cardiotoxicity from Chemotherapeutic Agents in Oncologic Disease.

PURPOSE OF REVIEW: In this review, we summarize the major known cardiac toxicities of common chemotherapeutic agents and the role of nuclear cardiac imaging for the surveillance and assessment of cancer therapeutics-related cardiac dysfunction in routine clinical practice. RECENT FINDINGS: Cardiotoxicity from chemotherapy causes a significant mortality and limits potentially life-saving treatment in cancer patients. Close monitoring of cardiac function during chemotherapy is an accepted method for reducing these adverse effects especially in patients with cancer therapeutics-related cardiac dysfunction. Nuclear imaging is a sensitive, specific, and highly reproducible modality for assessment of cardiac function. Nuclear imaging techniques including equilibrium radio nucleotide angiography, myocardial perfusion imaging, and novel experimental molecular imaging are the various objective tools available in addition to conventional echocardiography and cardiac magnetic resonance imaging in the surveillance, assessment, and follow-up of cancer therapeutics-related cardiac dysfunction.

Sex differences in heart failure hospitalisation risk following acute myocardial infarction.

OBJECTIVE: We evaluated the sex differences in 6-month heart failure (HF) hospitalisation risk in acute myocardial infarction (AMI) survivors. METHODS: For this retrospective cohort analysis, adult survivors of an AMI between January and June 2014 were identified from the US Nationwide Readmissions Database. The primary outcome was a HF hospitalisation within 6 months. Secondary outcomes were fatal HF hospitalisation and the composite of index in-hospital HF or 6-month HF hospitalisation. RESULTS: Of 237 549 AMI survivors, females (37.9%) were older (70±14 years vs 65±13 years; p<0.001), had a higher prevalence of cardiac comorbidities and a lower revascularisation rate compared with males. The primary outcome occurred in 12 934 patients (5.4%), at a 49% higher rate in females (6.8% vs 4.6% in males, p<0.001), which was attenuated to a 19% higher risk after multivariable adjustment. Findings were consistent across subgroups of age, AMI type and major risk factors. In the propensity-matched time-to-event analysis, female sex was associated with a 13% higher risk for 6-month HF readmission (6.4% vs 5.8% in males; HR 1.13, 95% CI 1.05 to 1.21, p<0.001), and the increased risk was evident early on after the AMI. Fatal HF rate was similar between groups (4.7% vs 4.6%, p=0.936), but females had a higher rate of the composite HF outcome (36.2% vs 27.5%, p<0.001). CONCLUSION: In a large all-comers AMI survivors' cohort, females had a higher HF hospitalisation risk that persisted after adjustment for baseline risk differences. This was consistent across several clinically relevant subgroups and was evident early on after the AMI.

Coronary artery disease in patients with human immunodeficiency virus infection.

The life expectancy of people infected with human immunodeficiency virus (HIV) is rising due to better access to combination anti-retroviral therapy (ART). Although ART has reduced acquired immune deficiency syndrome (AIDS) related mortality and morbidity, there has been an increase in non-AIDS defining illnesses such as diabetes mellitus, hypercholesterolemia and coronary artery disease (CAD). HIV is a disease marked by inflammation which has been associated with specific biological vascular processes increasing the risk of premature atherosclerosis. The combination of pre-existing risk factors, atherosclerosis, ART, opportunistic infections and coagulopathy contributes to rising CAD incidence. The prevalence of CAD has emerged as a major contributor of morbidity in these patients due to longer life expectancy. However, ART has been associated with lipodystrophy, dyslipidemia, insulin resistance, diabetes mellitus and CAD. These adverse effects, along with drug-drug interactions when ART is combined with cardiovascular drugs, result in significant challenges in the care of this group of patients. Exercise tolerance testing, echocardiography, myocardial perfusion imaging, coronary computed tomography angiography and magnetic resonance imaging help in the diagnosis of CAD and heart failure and help predict cardiovascular outcomes in a manner similar to non-infected individuals. This review will highlight the pathogenesis and factors that link HIV to CAD, presentation and treatment of HIV-patients presenting with CAD and review briefly the cardiac imaging modalities used to identify this entity and help prognosticate future outcomes.

Important role of annexin A2 (ANXA2) in new blood vessel development in vivo and human triple negative breast cancer (TNBC) growth.

Development of new blood vessels in the tumor microenvironment is an essential component of tumor progression during which newly formed blood vessels nourish tumor cells and play a critical role in rapid tumor growth, invasion and metastasis. Nevertheless, how tumor cells develop new blood vessels in the tumor microenvironment (TME) have been enigmatic. Previously, we have shown specific overexpression of ANX A2 in TNBC cells regulates plasmin generation and suspected a role in neoangiogenesis. In this report, we used Matrigel plug model of in vivo angiogenesis and confirmed its role in new blood vessel development. Next, we tested if blocking of ANX A2 in aggressive human breast TME can inhibit angiogenesis and tumor growth in vivo. We showed that aggressive human breast tumor cells growing in nude mice can induce intense neoangiogenesis in the tumor mass. Blocking of ANXA2 significantly inhibited neoangiogenesis and resulted in inhibition of tumor growth. Interestingly, we identified that blocking of ANXA2 significantly inhibited tyrosine phosphorylation (Tyr-P) of ANXA2 implying its involvement in tyrosine signaling pathway and suggesting it may regulate angiogenesis. Taken together, our experimental evidence suggests that ANX A2 could be a novel strategy for disruption of tyrosine signaling and inhibition of neoangiogenesis in breast tumor.

Impact of weight on the efficacy and safety of direct-acting oral anticoagulants in patients with non-valvular atrial fibrillation: a meta-analysis.

AIMS: This study sought to determine the impact of weight and body mass index (BMI) on the safety and efficacy of direct-acting oral anticoagulants (DOACs) compared with warfarin in patients with non-valvular atrial fibrillation. METHODS AND RESULTS: A systematic literature search was employed in PubMed, Embase, and Cochrane clinical trials with no language or date restrictions. Randomized trials or their substudies were assessed for relevant outcome data for efficacy that included stroke or systemic embolization (SSE), and safety including major bleeding and all-cause mortality. Binary outcome data and odds ratios from the relevant articles were used to calculate the pooled relative risk. For SSE, the data from the four Phase III trials showed that DOACs are better or similarly effective with low BMI 0.73 (0.56-0.97), normal BMI 0.72 (0.58-0.91), overweight 0.87 (0.76-0.99), and obese 0.87 (0.76-1.00). The risk of major bleeding was also better or similar with DOACs in all BMI subgroups with low BMI 0.62 (0.37-1.05), normal BMI 0.72 (0.58-0.90), overweight 0.83 (0.71-0.96), and obese 0.91 (0.81-1.03). There was no impact on mortality in all the subgroups. In a meta-regression analysis, the effect size advantage of DOACs compared with warfarin in terms of safety and efficacy gradually attenuated with increasing weight. CONCLUSION: Our findings suggest that a weight-based dosage adjustment may be necessary to achieve optimal benefits of DOACs for thromboembolic prevention in these patients with non-valvular atrial fibrillation. Further dedicated trials are needed to confirm these findings. PROSPERO 2019 CRD42019140693. Available from: https://www.crd.york.ac.uk/prospero/display_record.php? ID=CRD42019140693.

The role of cardiac imaging in the management of non-ischemic cardiovascular diseases in human immunodeficiency virus infection.

Infection with human immunodeficiency virus (HIV) has become the pandemic of the new century. About 36.9 million people are living with HIV worldwide. The introduction of antiretroviral therapy in 1996 has dramatically changed the global landscape of HIV care, resulting in significantly improved survival and changing HIV to a chronic disease. With near-normal life expectancy, contemporary cardiac care faces multiple challenges of cardiovascular diseases, disorders specific to HIV/AIDS, and those related to aging and higher prevalence of traditional risk factors. Non-ischemic cardiovascular diseases are major components of cardiovascular morbidity and mortality in HIV/AIDS. Non-invasive cardiac imaging plays a pivotal role in the management of these diseases. This review summarizes the non-ischemic presentation of the HIV cardiovascular spectrum focusing on the role of cardiac imaging in the management of these disorders.

Cardiovascular Outcomes With the Use of Sodium-Glucose Cotransporter-2 Inhibitors in Patients With Type 2 Diabetes and Chronic Kidney Disease: An Updated Meta-Analysis of Randomized Controlled Trials.

Diabetes mellitus (DM) and chronic kidney disease (CKD) significantly increase the risk of cardiovascular morbidity and mortality. Sodium-glucose cotransporter-2 (SGLT-2) inhibitors are a new class of hypoglycemic agents that have shown significant promise in the reduction of cardiovascular events. Current guideline recommendations do not support the use of these agents in patients with CKD stage 3 or higher. We performed a comprehensive meta-analysis to evaluate their cardiovascular effects in patients with type 2 DM and CKD stage 3 or higher. A comprehensive search was performed in PubMed, Cochrane central, and Embase. Software R was utilized to perform a meta-analysis via the generic inverse variance method. Additionally, we conducted a network meta-analysis to compare the relative efficacy and safety of each agent. Data from 7 randomized controlled trials and 6527 participants were available. In patients with type 2 DM and CKD, SGLT-2 inhibitor use resulted in a significant relative risk reduction of myocardial infarction (22%), heart failure hospitalization (39%), and major adverse cardiac events (20%) (all P-value < 0.05). There was also a trend towards a reduction in stroke and cardiovascular mortality. In a network meta-analysis, canagliflozin was the most effective in reducing myocardial infarction, stroke, and heart failure hospitalization. Empagliflozin performed better for the outcome of cardiovascular mortality, but the results failed to reach significance. In conclusion, SGLT-2 inhibitors significantly improve cardiovascular outcomes in patients with type 2 DM and CKD stage 3 or higher, providing a compelling reason for their use in this population subgroup.