Arrhythmia and Death Following Percutaneous Revascularization in Ischemic Left Ventricular Dysfunction: Prespecified Analyses From the REVIVED-BCIS2 Trial.

BACKGROUND: Ventricular arrhythmia is an important cause of mortality in patients with ischemic left ventricular dysfunction. Revascularization with coronary artery bypass graft or percutaneous coronary intervention is often recommended for these patients before implantation of a cardiac defibrillator because it is assumed that this may reduce the incidence of fatal and potentially fatal ventricular arrhythmias, although this premise has not been evaluated in a randomized trial to date. METHODS: Patients with severe left ventricular dysfunction, extensive coronary disease, and viable myocardium were randomly assigned to receive either percutaneous coronary intervention (PCI) plus optimal medical and device therapy (OMT) or OMT alone. The composite primary outcome was all-cause death or aborted sudden death (defined as an appropriate implantable cardioverter defibrillator therapy or a resuscitated cardiac arrest) at a minimum of 24 months, analyzed as time to first event on an intention-to-treat basis. Secondary outcomes included cardiovascular death or aborted sudden death, appropriate implantable cardioverter defibrillator (ICD) therapy or sustained ventricular arrhythmia, and number of appropriate ICD therapies. RESULTS: Between August 28, 2013, and March 19, 2020, 700 patients were enrolled across 40 centers in the United Kingdom. A total of 347 patients were assigned to the PCI+OMT group and 353 to the OMT alone group. The mean age of participants was 69 years; 88% were male; 56% had hypertension; 41% had diabetes; and 53% had a clinical history of myocardial infarction. The median left ventricular ejection fraction was 28%; 53.1% had an implantable defibrillator inserted before randomization or during follow-up. All-cause death or aborted sudden death occurred in 144 patients (41.6%) in the PCI group and 142 patients (40.2%) in the OMT group (hazard ratio, 1.03 [95% CI, 0.82-1.30]; P=0.80). There was no between-group difference in the occurrence of any of the secondary outcomes. CONCLUSIONS: PCI was not associated with a reduction in all-cause mortality or aborted sudden death. In patients with ischemic cardiomyopathy, PCI is not beneficial solely for the purpose of reducing potentially fatal ventricular arrhythmias. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01920048.

Cardiac energetics in patients with chronic heart failure and iron deficiency: an in-vivo 31 P magnetic resonance spectroscopy study.

AIMS: Iron deficiency (ID) is prevalent and adverse in chronic heart failure (CHF) but few human studies have explored the myocardial mechanism(s) that potentially underlie this adversity. Because mitochondrial oxidative phosphorylation (OXPHOS) provides over 90% of the hearts adenosine triphosphate (ATP), and iron is critical for OXPHOS, we hypothesized that patients with CHF and ID would harbour greater cardiac energetic impairments than patients without ID. METHODS AND RESULTS: Phosphorus magnetic resonance spectroscopy was used to quantify the phosphocreatine (PCr) to ATP (PCr/ATP) ratio, an index of in-vivo cardiac energetics, in CHF patients and healthy volunteers. Cardiac structure and function was assessed from magnetic resonance short stack cines. Patients with (n = 27) and without (n = 12) ID, and healthy volunteers (n = 11), were similar with respect to age and gender. The PCr/ATP ratio was lower in patients with ID (1.03 [0.83-1.38]) compared to those without ID (1.72 [1.51-2.26], p < 0.01) and healthy volunteers (1.39 [1.10-3.68], p < 0.05). This was despite no difference in cardiac structure and function between patients with and without ID, and despite adjustment for the presence of anaemia, haemoglobin levels, cardiac rhythm, or New York Heart Association (NYHA) class. In the total CHF cohort, the PCr/ATP ratio correlated with ferritin levels (rho = 0.4, p < 0.01), and was higher in NYHA class I than class II or III patients (p = 0.02). CONCLUSION: Iron deficiency is associated with greater cardiac energetic impairment in patients with CHF irrespective of anaemia and cardiac structure and function. Suppression of cardiac mitochondrial function might therefore be a mechanism via which ID worsens human CHF.

16S rDNA PCR for the aetiological diagnosis of culture-negative infective endocarditis.

INTRODUCTION: Culture-negative infective endocarditis (IE) accounts for 7-31% of all cases. Metagenomics has contributed to improving the aetiological diagnosis of IE patients undergoing valve surgery. We assessed the impact of 16S ribosomal DNA gene polymerase chain reaction (16S rDNA PCR) in the aetiological diagnosis of culture-negative IE. METHODS: Between January 2016 and January 2020, clinical data from culture-negative IE patients were reviewed retrospectively. Identification of bacteria was performed using 16S rDNA PCR in heart valve specimens. RESULTS: 36 out of 313 patients (12%) with culture-negative IE had their valve tissue specimens submitted for 16S rDNA PCR. 16S rDNA PCR detected and identified bacterial nucleic acid in heart valve tissue significantly more frequently compared to valve culture alone 25(70%) vs 5(12%); p < 0.05. Mean age was 57 years (SD 18) and 80% were male. Native and aortic valve were involved in 76% and 52% of cases, respectively. Streptococcus spp. (n 15) were the most commonly detected organisms, followed by bacteria of the HACEK group (Haemophilus parainfluenzae 2, Aggregatibacter actinomycetemcomitans 1), nutritionally variant streptococci (Abiotrophia defectiva 2), and one each of Staphylococcus aureus, Corynebacterium pseudodiphtheriticum, Helcococcus kunzii, Neisseria gonorrhoeae, Tropheryma whipplei. CONCLUSION: 16S rDNA PCR may be a useful diagnostic tool for the identification of the causative organism in culture-negative IE. Efforts towards a shorter turnaround time for results should be consider and further studies assessing the clinical impact of this technique in culture-negative IE are needed.

Diagnostic value of 18F-FDG PET/CT in infective endocarditis.

INTRODUCTION: 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET/CT) is not routinely recommended for the diagnosis of infective endocarditis (IE) due to the lack of clinical impact. MATERIALS AND METHODS: Between January 2016 and January 2020, clinical data from patients with a possible diagnosis of IE were reviewed retrospectively to evaluate the value of 18F-FDG-PET/CT in the diagnosis of IE. 18F-FDG PET/CT scan was performed as an additional diagnostic tool in possible IE when echocardiography was inconclusive or in patients with definite IE to identify extracardiac complications. Cases were classified according to modified Duke criteria as rejected, definite or possible. RESULTS: 313 patients with suspected IE were included. 72 (23%) patients underwent 18F-FDG PET/CT. 18F-FDG PET/CT resulted in a reclassification of Duke criteria in 29/72 (40%) patients, from "possible" to "definite" (n, 10) and to "rejected" (n, 19). Patients who benefited from a Duke criteria reclassification following 18F-FDG PET/CT were more frequently classified as possible IE at inclusion or had a non-conclusive baseline echocardiography (100% vs 58%; p 0.001) and had more likely a prosthetic metallic valve replacement (59% vs 21%; p 0.001). Abnormal perivalvular uptake was identified in 46 patients (71% prosthetic vs 50% native; p 0.118). 18F-FDG PET/CT identified extracardiac uptake consistent with septic emboli in 14/72 (19%) patients. In addition, extracardiac uptake indicative of an alternative diagnosis was identified in 5 patients (2% prosthetic vs 17% native; p 0.039). CONCLUSION: The use of 18F-FDG-PET/CT has shown to be useful in the diagnosis of IE, particularly in prosthetic IE and may provide additional value in the detection of septic emboli and/or the identification of an alternative diagnosis different from IE.

Isolated papillary muscle rupture with nonobstructive coronary artery disease, minimal myocardial infarction, and normal wall motion.

Papillary muscle (PM) rupture can usually complicate inferior or posterior myocardial infarctions, but selective PM infarction is extremely rare, and the exact underlying pathophysiological mechanism is not entirely clear. We present a case of PM rupture due to isolated PM infarction in a patient with unobstructed coronary arteries, which could be misdiagnosed as a vegetation or other mass given the absence of regional wall motion abnormalities (RWMAs) on transthoracic echocardiogram. Our case highlights that in patients with severe mitral regurgitation and associated mitral valve mass, the absence of RWMAs should not exclude ischemic PM rupture from differential diagnosis.

Tissue Doppler-Derived Left Ventricular Systolic Velocity Is Associated with Lethal Arrhythmias in Cardiac Device Recipients Irrespective of Left Ventricular Ejection Fraction.

BACKGROUND: Life-threatening arrhythmias (LTAs) can trigger sudden cardiac death or provoke implantable cardioverter-defibrillator (ICD) discharges that escalate morbidity and mortality. Longitudinal myofibrils predominate in the subendocardium, which is uniquely sensitive to arrhythmogenic triggers. In this study, we test the hypothesis that mitral annular systolic velocity (S'), a simple routinely obtained tissue Doppler index of LV long-axis systolic function, might predict lethal arrhythmias irrespective of left ventricular ejection fraction (LVEF). METHODS: This is a retrospective analysis of data from 302 patients (mean age, 68 years; LVEF, 32%; 77% male; 52% ischemic; 35% primary prevention; and 53% cardiac resynchronization therapy defibrillator [CRT-D]) who were followed up (median, 15 months) at two centers after receipt of an ICD or CRT-D for diverse indications. S', averaged from tissue Doppler-derived medial and lateral mitral annular velocities, was correlated with the primary outcome of time to sustained ventricular tachycardia (VT) or fibrillation (VF) needing device therapy. RESULTS: The median S' was 5.1 (interquartile range, 4.0-6.2) cm/sec and lower in CRT-D than ICD subjects (4.5 [3.8-5.6] cm/sec vs 5.5 [4.8-6.8] cm/sec, P < .001). Fifty-six (19%) subjects had LTA. Each 1 cm/sec higher S' correlated to a 30% decreased risk of LTA (hazard ratio = 0.70; 95% CI, 0.57-0.87; P = .001) independently of age, sex, ß-blocker use, center, ICD use, and LVEF. Adding S' to the baseline Cox model improved net reclassification (P = .02). An S' > 5.6 cm/sec was the best cutoff and linked to a 58% lower LTA risk than an S' ≤ 5.6 cm/sec (95% CI, 0.23-0.85; P = .02). CONCLUSIONS: A higher S' is associated with a reduced probability of LTA in cardiac device recipients irrespective of LVEF and may have the potential to be used clinically to titrate medical, device, and ablative therapies to mitigate future arrhythmic risk.

Calculated plasma volume status and outcomes in patients undergoing coronary bypass graft surgery.

OBJECTIVES: Congestion is associated with worse outcomes in critically ill surgical patients but can be difficult to quantify noninvasively. We hypothesised that plasma volume status (PVS), estimated preoperatively using a validated formula that enumerates percentage change from ideal plasma volume (PV), would provide incremental prognostic utility after coronary artery bypass graft (CABG) surgery. METHODS: In this retrospective cohort study, patients who underwent CABG surgery (1999-2010) were identified from a prospectively collected database. Actual ([1-haematocrit] x [a+(b x weight [kg])]) and ideal (c x weight [kg]) PV were obtained from equations where a, b and c are sex-dependent constants. Calculated PVS was then derived (100% x [(actual-ideal)/ideal]). RESULTS: In 1887 patients (mean age 67±10 years; 79% male; median European System for Cardiac Operative Risk Evaluation [EuroSCORE] 4), mean PVS was -8.2±9%. While 8% of subjects had clinical evidence of congestion, a relatively increased PV (PVS >0%) was estimated in 17% and correlated with lower serum sodium, higher EuroSCORE and a diagnosis of diabetes mellitus. A PVS≥5.6% was optimally prognostic and associated with greater mortality (HR: 2.31, p=0.009), independently of, and incremental to, EuroSCORE, New York Heart Association class and serum sodium. A PVS≥5.6% also independently predicted longer intensive care (ß: 0.65, p=0.007) and hospital (ß: 2.01, p=0.006) stays, and greater postoperative renal (OR: 1.61, p=0.008) and arrhythmic (OR: 1.29, p=0.03) complications. CONCLUSIONS: Higher PVS values, calculated simply from weight and haematocrit, are associated with worse inpatient outcomes after CABG. PVS could help refine risk stratification and further investigations are warranted to evaluate the potential clinical utility of PVS-guided management in patients undergoing CABG.

Effect of Iron Isomaltoside on Skeletal Muscle Energetics in Patients With Chronic Heart Failure and Iron Deficiency.

BACKGROUND: Iron repletion augments exercise capacity in chronic heart failure (HF), but there is a lack of mechanistic data explaining how iron could augment exercise performance despite minimal changes in hemoglobin (Hb). Besides Hb, iron is an obligate component of mitochondrial enzymes that generate cellular energy in the form of adenosine triphosphate and phosphocreatine (PCr). Dynamic phosphorus magnetic resonance spectroscopy is a noninvasive tool that quantifies in vivo muscle energetics by measuring the kinetics of PCr recovery after exertion. We tested the hypothesis that intravenous iron repletion in chronic HF enhances skeletal muscle energetics as reflected by shorter PCr recovery half-times (PCr t1/2) on phosphorus magnetic resonance spectroscopy. METHODS: We enrolled 40 patients (50% anemic) with chronic HF, New York Heart Association class ≥II, left ventricular ejection fraction ≤45%, and iron deficiency (ferritin<100 µg/L or 100-300 µg/L with transferrin saturation <20%). Subjects underwent stratified (anemic versus nonanemic) randomization (1:1) to a single, double-blinded, total dose infusion of iron isomaltoside or saline placebo with end points reassessed early at 2 weeks posttreatment to minimize confounding from exercise adaptation. The primary end point was PCr t1/2 at 2 weeks. Secondary end points included ADP recovery half-time (ADP t1/2; energetic marker), iron status, symptoms, Hb, exercise capacity, and safety. RESULTS: In the total population, treatment groups were similar at baseline. At 2 weeks, iron isomaltoside improved PCr t1/2 (adjusted difference, -6.8 s; 95% CI, 11.5 to -2.1; P=0.006), ADP t1/2 (-5.3 s; 95% CI, -9.7 to -0.9; P=0.02), ferritin (304 ng/mL; 95% CI, 217-391; P<0.0001), transferrin saturation (6.8%; 95% CI, 2.7-10.8; P=0.002), New York Heart Association class (-0.23; 95% CI, -0.46 to -0.01; P=0.04), resting respiratory rate (-0.7 breaths/min; 95% CI, -1.2 to -0.2; P=0.009), and postexercise Borg dyspnea score (-2.0; 95% CI, -3.7 to -0.3; P=0.04), but not Hb (2.4 g/L; 95% CI, -3.5 to 8.4; P=0.41). Adverse events were similar between groups. In subgroup analyses, iron isomaltoside improved PCr t1/2 in anemic (-8.4 s; 95% CI, -16.7 to -0.2; P=0.04) and nonanemic (-5.2 s; 95% CI, -10.6 to 0.2; P=0.06) cohorts. CONCLUSIONS: In patients with chronic HF and iron deficiency, a total repletion dose of iron isomaltoside given at a single sitting is well tolerated and associated with faster skeletal muscle PCr t1/2 at 2 weeks, implying better mitochondrial function. Augmented skeletal muscle energetics might therefore be an important mechanism via which iron repletion confers benefits in chronic HF despite minimal Hb changes. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2012-005592-13/GB . Unique identifier: EudraCT 2012-005592-13.

Biologic Variability of Soluble ST2 in Patients With Stable Chronic Heart Failure and Implications for Monitoring.

Soluble ST2 (sST2) is a novel biomarker implicated in myocardial remodeling and fibrosis. Recent studies in normal subjects have suggested that the biologic variability (BV) of sST2 is significantly lower than that of the B-type natriuretic peptides and N-terminal pro B-type natriuretic peptide (NTproBNP). It may, consequently, be a better biomarker for monitoring patients with chronic heart failure (CHF). To date, no published studies have examined the BV of sST2 in a heart failure population. Blood samples from 50 outpatients with pharmacologically optimized stable CHF and persistent left ventricular dysfunction (ejection fraction <40%) were collected at baseline, 1 hour, 1 month, 3 months, and 6 months. Using log-transformed data, mean intra-individual coefficients of variation (CVI) and subsequent reference change values were calculated for both NTproBNP and sST2. Results demonstrate significantly lower CVI and reference change values for sST2 compared with NTproBNP at 1 month (12.02 [36%] vs 36.75 [103%]), p <0.001, 3 months (12.23 [36%] vs 40.98 [114%]), p <0.001, and 6 months (16.41 [47%] vs 46.02 [128%]), p <0.001. In conclusion, the BV of sST2 is significantly lower than that of NTproBNP in patients with CHF. These results support previous indications that sST2 may be a better biomarker for monitoring such patients.

Serial soluble ST2 for the monitoring of pharmacologically optimised chronic stable heart failure.

BACKGROUND: Soluble ST2 (sST2) is an emerging biomarker of cardiac remodelling and fibrosis. Studies indicate that it is predictive of mortality in acutely decompensated heart failure. The role of sST2 in chronic heart failure (CHF) is less well defined. No studies have examined serial measurements in optimised patients as a potential monitoring tool. This study aimed to prospectively determine the prognostic utility of serial sST2 in patients with pharmacologically optimised stable CHF. METHODS: 41 patients with pharmacologically optimised CHF and left ventricular ejection fraction ≤40% were recruited. Clinical review and blood sampling took place at baseline, and one, three and six months. N-terminal pro-brain natriuretic peptide (NTproBNP), sST2 and renal profile were measured on all samples. 12 lead electrocardiogram (ECG) was performed at baseline. Decompensation was defined as a composite endpoint of cardiovascular admission or worsening renal function (≥25% increase in serum creatinine from baseline). RESULTS: Receiver operator curve analysis of percentage change in sST2 from baseline to six months was strongly reflective of decompensation with area under the curve (AUC) of 0.778. This was significantly better than NTproBNP (AUC 0.425; p=0.013). Correlation of baseline concentrations to surface ECG showed that both sST2 and NTproBNP were positively correlated with duration of the QRS wave, with higher level of significance demonstrated by sST2 (0.415 (p=0.007) and 0.362 (p=0.020) respectively). CONCLUSIONS: Percentage changes in sST2 are better able to predict cardiovascular admission or worsening renal function in patients with pharmacologically optimised CHF than NTproBNP. Compared with NTproBNP, sST2 appears to be a promising candidate for monitoring these patients.