The nature of cachexia in patients with heart failure and stable coronary artery disease

Cachexia is a prognostically important development in patients with heart failure. The most commonly used definition of cardiac cachexia is loss of a percentage of body weight over time. Muscle wasting has been assumed to be the major contributor to this weight loss, and cytokine activation is postulated to be central to the pathogenesis. We hypothesised that elevated circulating cytokines in cachectic heart failure patients would be associated with muscle inflammation, injury and impaired ability to repair. The aim of this doctoral work was to characterise the nature of cachexia in patients with heart failure (HF) and stable coronary artery disease (CAD), to quantify the loss of muscle mass, and test the hypothesis that muscle wasting is mediated by the activation of tissue cytokines and cell cycle inhibitors. We studied five subject groups. Three were groups of patients with stable coronary artery disease: 1) HF-cachexia - patients with HF, reduced left ventricular systolic function and cachexia, n=10; 2) HF-no cachexia - those with HF, reduced systolic function but no cachexia, n=20; and 3) CAD - those with CAD, no symptoms of HF and preserved systolic function, n=10. The other subject groups were: 4) IDCM - patients with idiopathic dilated cardiomyopathy, n=7; and 5) HC - healthy controls, n=9. Subjects were characterised by New York Heart Association (NYHA) classification, left ventricular ejection fraction (LVEF), peak oxygen consumption (VO2), weight history and body composition analysis. Circulating levels of tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), C-reactive protein (CRP), leptin, adiponectin, and Btype natriuretic peptide (BNP) were measured. Skeletal muscle biopsies were analysed for the expression of messenger ribonucleic acid (mRNA) for TNF-α, IL-6, interleukin-1β (IL-1β), interleukin-18 (IL-18) and the cell cycle inhibitors (cyclin dependent kinase (CDK) inhibitors) p21, p27 and p57. We found that the HF-cachexia group had significantly lower body mass index (BMI) and percentage body fat than all the other subject groups. In contrast, there was no significant reduction in fat free mass index (FFMI). In addition, the HF-cachexia group had higher rates of fat oxidation than all other groups. While the HF-cachexia group had elevated circulating levels of TNF-α and IL-6, there was no increased expression of cytokines or CDK inhibitors in the skeletal muscle. Circulating adiponectin and BNP levels were elevated in the HF-cachexia group. There was a positive association between adiponectin and BNP, and a negative relationship of each with BMI and percentage body fat. In addition, adiponectin positively correlated with rate of fat oxidation and TNF-α concentration. A possible causal relationship between adiponectin and increased rate of fat oxidation was further investigated in an additional study of young healthy male subjects performing an exercise program specifically designed to maximise fat metabolism (n=11). Despite inducing significantly increased rates of fat oxidation and adiponectin concentrations no relationship was observed between them. In conclusion, cachexia in patients with heart failure and stable coronary artery disease predominantly involves the loss of adipose tissue, with no evidence of muscle wasting or inflammation. The presence of increased circulating levels of adiponectin and BNP, their association with each other, and the relationship of each with body composition, energy metabolism and TNF-α suggests these peptides may play an important role in the pathogenesis of cardiac cachexia

Chest pain without obstructive coronary artery disease: a case series report

Background: Ischaemic heart disease is a leading cause of mortality in women. Even in those without obstructive coronary artery disease (CAD), women with angina continue to have increased mortality. There are gender differences in prevalence of different pathophysiologies, including functional disorders such as microvascular and vasospastic angina. Case summary: We describe four cases of angina in women with no obstructive CAD, in whom coronary function testing was performed. These four patients were diagnosed with disorders of coronary vasomotion, including vasospastic angina and different endotypes of microvascular angina. Discussion: This case series highlights the different mechanisms of ischaemia in the absence of obstructive CAD. Patients with angina and no obstructive CAD classified by computed tomography coronary angiography may have myocardial ischaemia due to microvascular angina, vasospastic angina, or both. Conventional investigations risk under-diagnosing, and as a consequence under-treating, patients with these conditions. Coronary function testing, in the form of diagnostic guidewire-based tests and adjunctive acetylcholine provocation, has proven to be critical in the accurate diagnoses and appropriate management of these patients

Arterial access for invasive coronary angiography: the 'left backhander'

No abstract available

Single versus two-stent strategies for coronary bifurcation lesions: a systematic review and meta-analysis of randomized trials with long-term follow-up

Background: The majority of coronary bifurcation lesions are treated with a provisional single‐stent strategy rather than an up‐front 2‐stent strategy. This approach is supported by multiple randomized controlled clinical trials with short‐ to medium‐term follow‐up; however, long‐term follow‐up data is evolving from many data sets. Methods and Results: Meta‐analysis of randomized controlled trials evaluating long‐term outcomes (≥1 year) according to treatment strategy for coronary bifurcation lesions. Nine randomized controlled trials with 3265 patients reported long‐term clinical outcomes at mean weighted follow‐up of 3.1±1.8 years. Provisional single stenting was associated with lower all‐cause mortality (2.94% versus 4.23%; risk ratio: 0.69; 95% confidence interval, 0.48–1.00; P=0.049; I2=0). There was no difference in major adverse cardiac events (15.8% versus 15.4%; P=0.79), myocardial infarction (4.8% versus 5.5%; P=0.51), target lesion revascularization (9.3% versus 7.6%; P=0.19), or stent thrombosis (1.8% versus 1.6%; P=0.28) between the groups. Prespecified sensitivity analysis of long‐term mortality at a mean of 4.7 years of follow‐up showed that the provisional single‐stent strategy was associated with reduced all‐cause mortality (3.9% versus 6.2%; risk ratio: 0.63; 95% confidence interval, 0.42–0.97; P=0.036; I2=0). Conclusions: Coronary bifurcation percutaneous coronary intervention using a provisional single‐stent strategy is associated with a reduction in all‐cause mortality at long‐term follow‐up

Left ventricular outcomes following multivessel PCI vs. infarct artery-only PCI in patients with acute STEMI: the Glasgow PRAMI CMR sub-study

No abstract available

TCT-121 Extraplaque Versus Intraplaque Tracking in Chronic Total Occlusion Percutaneous Coronary Intervention

Background: The impact of modern extraplaque (EP) tracking techniques on long-term outcomes remains controversial. Methods: We performed a systematic review and meta-analysis of studies that compared EP vs intraplaque (IP) tracking in CTO PCI. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using the Der-Simonian and Laird random-effects method. Results: Our meta-analysis included seven observational studies with 2,982 patients. Patients who underwent EP tracking had significantly more complex CTOs with higher J-CTO scores (2.9 ± 1.2 vs 1.6 ± 1.1, P \u3c 0.001), longer lesion length, more severe calcification, and significantly longer stented segments. During a median follow-up of 12 months (range 9-12 months), EP tracking was associated with a higher risk of major adverse cardiovascular events (MACE) (OR 1.50, 95% CI 1.10-2.06, P = 0.01) and target vessel revascularization (TVR) (OR 1.69, 95% CI 1.15-2.48, P = 0.01) compared with IP tracking. There was no difference in the incidence of all-cause death (OR 1.37, 95% CI 0.67-2.78, P = 0.39), myocardial infarction (MI) (OR 1.48, 95% CI 0.82-2.69, P = 0.20), or stent thrombosis (OR 2.09, 95% CI 0.69-6.33, P = 0.19) between EP and IP tracking. Conclusion: Compared with IP tracking, EP tracking was utilized in more complex and longer CTOs, required more stents, and was associated with a higher risk of MACE at 12 months, driven by a higher risk of TVR, but without an increased risk of death or MI. Categories: CORONARY: Complex and Higher Risk Procedures for Indicated Patients (CHIP

Infarct size and left ventricular remodelling after preventive percutaneous coronary intervention

Objective: We hypothesised that, compared with culprit-only primary percutaneous coronary intervention (PCI), additional preventive PCI in selected patients with ST-elevation myocardial infarction with multivessel disease would not be associated with iatrogenic myocardial infarction, and would be associated with reductions in left ventricular (LV) volumes in the longer term. Methods: In the preventive angioplasty in myocardial infarction trial (PRAMI; ISRCTN73028481), cardiac magnetic resonance (CMR) was prespecified in two centres and performed (median, IQR) 3 (1, 5) and 209 (189, 957) days after primary PCI. Results: From 219 enrolled patients in two sites, 84% underwent CMR. 42 (50%) were randomised to culprit-artery-only PCI and 42 (50%) were randomised to preventive PCI. Follow-up CMR scans were available in 72 (86%) patients. There were two (4.8%) cases of procedure-related myocardial infarction in the preventive PCI group. The culprit-artery-only group had a higher proportion of anterior myocardial infarctions (MIs) (55% vs 24%). Infarct sizes (% LV mass) at baseline and follow-up were similar. At follow-up, there was no difference in LV ejection fraction (%, median (IQR), (culprit-artery-only PCI vs preventive PCI) 51.7 (42.9, 60.2) vs 54.4 (49.3, 62.8), p=0.23), LV end-diastolic volume (mL/m2, 69.3 (59.4, 79.9) vs 66.1 (54.7, 73.7), p=0.48) and LV end-systolic volume (mL/m2, 31.8 (24.4, 43.0) vs 30.7 (23.0, 36.3), p=0.20). Non-culprit angiographic lesions had low-risk Syntax scores and 47% had non-complex characteristics. Conclusions: Compared with culprit-only PCI, non-infarct-artery MI in the preventive PCI strategy was uncommon and LV volumes and ejection fraction were similar

Microvascular resistance predicts myocardial salvage and infarct characteristics in ST-elevation myocardial infarction

<b>Background:</b> The pathophysiology of myocardial injury and repair in patients with ST‐elevation myocardial infarction is incompletely understood. We investigated the relationships among culprit artery microvascular resistance, myocardial salvage, and ventricular function.<p></p> <b>Methods and Results:</b> The index of microvascular resistance (IMR) was measured by means of a pressure‐ and temperature‐sensitive coronary guidewire in 108 patients with ST‐elevation myocardial infarction (83% male) at the end of primary percutaneous coronary intervention. Paired cardiac MRI (cardiac magnetic resonance) scans were performed early (2 days; n=108) and late (3 months; n=96) after myocardial infarction. T2‐weighted‐ and late gadolinium–enhanced cardiac magnetic resonance delineated the ischemic area at risk and infarct size, respectively. Myocardial salvage was calculated by subtracting infarct size from area at risk. Univariable and multivariable models were constructed to determine the impact of IMR on cardiac magnetic resonance–derived surrogate outcomes. The median (interquartile range) IMR was 28 (17–42) mm Hg/s. The median (interquartile range) area at risk was 32% (24%–41%) of left ventricular mass, and the myocardial salvage index was 21% (11%–43%). IMR was a significant multivariable predictor of early myocardial salvage, with a multiplicative effect of 0.87 (95% confidence interval 0.82 to 0.92) per 20% increase in IMR; P<0.001. In patients with anterior myocardial infarction, IMR was a multivariable predictor of early and late myocardial salvage, with multiplicative effects of 0.82 (95% confidence interval 0.75 to 0.90; P<0.001) and 0.92 (95% confidence interval 0.88 to 0.96; P<0.001), respectively. IMR also predicted the presence and extent of microvascular obstruction and myocardial hemorrhage.<p></p> <b>Conclusion:</b> Microvascular resistance measured during primary percutaneous coronary intervention significantly predicts myocardial salvage, infarct characteristics, and left ventricular ejection fraction in patients with ST‐elevation myocardial infarction.<p></p&gt

TCT-118 Comparative Analysis of Patients’ Characteristics in Chronic Total Occlusion Revascularization Studies: Trials Versus Real-World Registries

Background: The few randomized controlled trials (RCTs) on chronic total occlusion (CTO) percutaneous coronary interventions (PCI) are subject to selection bias. Methods: We performed a meta-analysis of national and dedicated CTO PCI registries and compared patient characteristics and outcomes with those of RCTs that randomized patients to CTO PCI vs medical therapy. Given the large sample size differences between RCTs and registries, we focused on the absolute numbers and their clinical significance. We considered a 5% relative difference between groups to be potentially clinically relevant. Results: From 2012 to 2022, 6 RCTs compared CTO PCI vs medical therapy (n = 1,047) and were compared with 15 registries (5 national and 10 dedicated CTO PCI registries). Compared with registry patients, RCT patients had fewer comorbidities, including diabetes, hypertension, previous myocardial infarction, and prior coronary artery bypass graft surgery. RCT patients had shorter CTO length (29.6 ± 19.7 vs 32.6 ± 23.0 mm, a relative difference of 9.2%) and lower J-CTO scores (2.0 ± 1.1 vs 2.3 ± 1.2, a relative difference of 13%) compared with those enrolled in dedicated CTO registries. Procedural success was similar between RCTs (84.5%) and dedicated CTO registries (81.4%) but was lower in national registries (63.9%). Conclusion: There is a paucity of randomized data on CTO PCI outcomes (6 RCTs, 1,047 patients). These patients have lower-risk profiles and less complex CTOs than those in real-world registries. Current evidence from RCTs may not be representative of real-world patients and should be interpreted within its limitation. Categories: CORONARY: Complex and Higher Risk Procedures for Indicated Patients (CHIP

Safety of guidewire-based measurement of fractional flow reserve and the index of microvascular resistance using intravenous adenosine in patients with acute or recent myocardial infarction

Aims: Coronary guidewire-based diagnostic assessments with hyperemia may cause iatrogenic complications. We assessed the safety of guidewire-based measurement of coronary physiology, using intravenous adenosine, in patients with an acute coronary syndrome. Methods: We prospectively enrolled invasively managed STEMI and NSTEMI patients in two simultaneously conducted studies in 6 centers (NCT01764334; NCT02072850). All of the participants underwent a diagnostic coronary guidewire study using intravenous adenosine (140 μg/kg/min) infusion for 1–2 min. The patients were prospectively assessed for the occurrence of serious adverse events (SAEs) and symptoms and invasively measured hemodynamics were also recorded. Results: 648 patients (n = 298 STEMI patients in 1 hospital; mean time to reperfusion 253 min; n = 350 NSTEMI in 6 hospitals; median time to angiography from index chest pain episode 3 (2, 5) days) were included between March 2011 and May 2013. Two NSTEMI patients (0.03% overall) experienced a coronary dissection related to the guidewire. No guidewire dissections occurred in the STEMI patients. Chest symptoms were reported in the majority (86%) of patient's symptoms during the adenosine infusion. No serious adverse events occurred during infusion of adenosine and all of the symptoms resolved after the infusion ceased. Conclusions: In this multicenter analysis, guidewire-based measurement of FFR and IMR using intravenous adenosine was safe in patients following STEMI or NSTEMI. Self-limiting symptoms were common but not associated with serious adverse events. Finally, coronary dissection in STEMI and NSTEMI patients was noted to be a rare phenomenon