Growth hormone for risk stratification and effects of therapy in acute myocardial infarction.

CONTEXT: Excess growth hormone (GH) is associated with early mortality. OBJECTIVES: We assessed the association of GH with prognosis after acute myocardial infarction (AMI), and the effects of secondary prevention therapies. METHODS: GH was measured using a high-sensitivity assay in 953 AMI patients (687 males, mean age 66.1 ± 12.8 years). RESULTS: During 2 years follow-up, there were 281 major adverse cardiac events (MACE). Patients with MACE had higher GH levels (median [range], 0.91 [0.04-26.28] µg/L) compared to event-free survivors (0.59 [0.02-21.6], p < 0.0005). In multivariate Cox survival analysis, GH was a significant predictor of MACE (hazard ratios 1.43, p = 0.026 and 1.49, p = 0.01, respectively) with significant interactions with beta blocker therapy (p = 0.047) and angiotensin converting enzyme inhibitor or angiotensin receptor blocker (ACE/ARB) therapy (p = 0.016). CONCLUSIONS: GH levels post-AMI are prognostic for MACE and may indicate those patients who benefit from beta blocker and ACE/ARB therapy.

Influence of confounding factors on plasma mid-regional pro-adrenomedullin and mid-regional pro-A-type natriuretic peptide concentrations in healthy individuals.

BACKGROUND: MRproADM and MRproANP can be used as diagnostic and prognostic markers in heart failure. AIM: The objective was to identify confounding factors for the interpretation of plasma MRproADM and MRproANP concentrations. METHODS: A total of 518 healthy volunteers with a mean age of 60.84 ± 7.41 years were analyzed. We evaluated the influence of demographic factors, renal function and echocardiographic indices on the candidate peptides. RESULTS: Multivariate analysis revealed that age (P < 0.001), BMI (P < 0.001) and eGFR (P < 0.001) were independent predictors for MRproADM concentrations in healthy subjects. The independent predictors for MRproANP were age (P < 0.001), female gender (P < 0.001), heart rate (P < 0.001) and eGFR (P = 0.039). CONCLUSION: The interpretation of both peptides is multifaceted due to confounders. Knowledge of these factors will further our understanding of how these peptides behave in health and in disease.

Improving quality and reducing inequality in heart failure.

The popular annual autumn meeting of the British Society for Heart Failure (BSH) boasted a line-up of internationally recognised authorities in heart failure. Held in London on 28th-29th November 2019, the meeting's focus was on improving quality and reducing inequality. Drs Sanjay S Bhandari and Daniel CS Chan report its highlights.

Gender and renal function influence plasma levels of copeptin in healthy individuals.

The present study sought to identify confounding factors for the interpretation of copeptin levels in healthy individuals. The natriuretic peptides are recognized as diagnostic and prognostic tools in HF (heart failure). Interpretation of BNP (brain natriuretic peptide) and NTproBNP (N-terminal pro-BNP) levels is multifaceted as their secretion is influenced by many variables. A newly identified glycopeptide called copeptin is comparable with the natriuretic peptides in the diagnosis and prognosis of HF and as a prognostic biomarker after AMI (acute myocardial infarction). Copeptin, derived from the C-terminal portion of the precursor to AVP (arginine vasopressin), is secreted stoichiometrically with vasopressin, hence it can be used as a surrogate marker of the AVP system. In the present study, 706 healthy volunteers were recruited from a local HF screening study. Participants with a history of cardiovascular disease and those with echocardiographic abnormalities were excluded from the study. Copeptin and NTproBNP levels were assayed using in-house immunoluminometric assays. Median copeptin levels were significantly higher in the male volunteers compared with the females [median (range): 4.3 (0.4-44.3) compared with 3.2 (1.0-14.8) pmol/l; P<0.001]. In males, copeptin was correlated with eGFR (estimated glomerular filtration rate; r(s)=-0.186, P<0.001). In females, the correlation of copeptin with eGFR was weak (r(s)=-0.097, P=0.095). DT (deceleration time) and left atrial size correlated with higher copeptin levels (r(s)=0.085, P=0.029 and r(s)=0.206, P<0.001 respectively). Only gender (P<0.001), eGFR (P<0.001), left atrial size (P=0.04) and DT (P=0.02) remained independently predictive of plasma copeptin. The present study suggests that gender and renal function specific partition values should be used to interpret copeptin values in future studies of this biomarker in HF or ischaemic heart disease.

Recurrent valve obstruction in a patient with a pure carbon bileaflet metallic mitral valve: a case report.

BACKGROUND: Despite overcoming the morbidity from severe native valve disease, prosthetic metallic valve replacement is not without its inherent morbidity, in particular from prosthetic valve thrombosis (PVT). The contemporary pure carbon bileaflet metallic valve confers reduced thrombogenicity. CASE SUMMARY: We describe the case of a 45-year-old woman with a pure carbon bileaflet metallic mitral valve replacement (27/29 mm On-X) 6 months previously for severe rheumatic mitral stenosis, who presented with a rapid onset of dyspnoea, paroxysmal nocturnal dyspnoea, and haemoptysis. This was preceded by an interruption in therapeutic anticoagulation. On admission the patient was in cardiogenic shock. Transthoracic and transoesophageal (TOE) echocardiograms revealed increased transmitral gradients with disc hypomobility, suggestive of PVT, unexpected given the favourable safety profile of the On-X valve. Fluoroscopy confirmed the findings. The patient was thrombolysed successfully with alteplase, with restoration of normal transmitral gradients. A target international normalized ratio of 3.5-4.5 was chosen, in addition to aspirin 75 mg, to minimize thrombotic sequalae. Repeat TOE 6 weeks later revealed disc hypomobilty with a large adherent clot. Due to the high risks from thrombolysis, emergency redo-mitral bioprosthetic valve surgery was performed, to negate the need for long-term anticoagulation. DISCUSSION: Subtherapeutic anticoagulation and the rapid development of dyspnoea, should prompt the clinician to suspect PVT. Thorough clinical examination and immediate bedside echocardiography are critical for assessing prosthetic valve patients in cardiogenic shock. The treatment of PVT is complex, with considerable risks to the patient, irrespective of the strategy (thrombolysis/emergency valve replacement), necessitating the expertise of cardiologists and cardiac surgeons.

Mesalazine induced myopericarditis in a patient with ulcerative colitis.

A 25-year-old male with a background of ulcerative colitis presented with a two-week history of central chest pain. His ECG on presentation showed global T wave inversion with a peak troponin I of 165 ng/ml. Clinical diagnosis of myopericarditis/myocarditis was made. Echocardiography and cardiac MR confirmed the diagnosis. On detailed assessment of his medication history, mesalazine was suspected as an aetiological factor, with discontinuation resulting in an improvement in symptoms, inflammatory markers and cardiac enzymes. This is a unique case of mesalazine induced myopericarditis on a background of inflammatory bowel disease.

An uncommon manifestation of shock: Takotsubo syndrome.

76-year-old female presented following an episode of collapse. She was hypotensive with the paramedics and remained refractory despite fluid resuscitation. Her initial baseline tests revealed an elevated troponin; she subsequently underwent a coronary angiogram that showed mild coronary artery disease. Left ventriculogram was performed, which showed abnormal mid-wall ballooning and severely impaired systolic function, characteristic of Takotsubo syndrome. Echocardiogram confirmed the presence of diagnosis and presence of left ventricular outflow tract obstruction with high gradient. She was initiated on medical heart failure therapy and improved. Follow-up investigations after 2 months showed complete resolution of systolic dysfunction and symptoms. LEARNING POINTS: Takotsubo syndrome can present similarly to ACS.Early use of echocardiography in the acute setting can provide vital information.Takotsubo syndrome can result in hemodynamic instability requiring urgent interventions.Other investigative modalities can be used in conjunction with echocardiography to confirm the diagnosis of Takotsubo syndrome.Prognosis is generally good in patients with Takotsubo syndrome.

Critical aortic stenosis presenting as STEMI.

A 73-year-old male was brought into hospital with chest pain and inferior ST elevation on ECG. The patient immediately proceeded to the catheter lab for primary percutaneous coronary intervention. Angiography did not identify any culprit lesions to account for the patient's electrocardiographic changes and ongoing symptoms of chest pain. Bedside echocardiography revealed critical aortic stenosis. Intra-aortic balloon pump (IABP) was inserted, resulting in resolution of chest pain and ST-segment changes. The patient underwent successful aortic valve (AV) replacement without the need for coronary intervention. This is a rare presentation of critical aortic stenosis (AS) presenting as ST-segment elevation myocardial infarction (STEMI). LEARNING POINTS: Aortic stenosis (AS) affects 2-9% of population above 65 years old and increases with age.AS induces ischaemia via abnormal cardiac coronary coupling.Focused clinical examination in patients with ST-segment elevation myocardial infarction (STEMI) is vital prior to cardiac catheterisation.Detection of murmurs should be followed on by an echocardiography examination.Other differentials of STEMI include acute aortopathy, endocarditis with embolus, myopericarditis and intracranial haemorrhage.

Trimethylamine N-oxide and prognosis in acute heart failure.

OBJECTIVE: Acute heart failure (AHF) is associated with high mortality and morbidity. Trimethylamine N-oxide (TMAO), a gut-derived metabolite, has reported association with mortality risk in chronic HF but this association in AHF is still unknown. The present study investigated TMAO in patients admitted to hospital with AHF, and association of circulating levels with prognosis. METHODS: In total, 972 plasma samples were analysed for TMAO concentration by liquid chromatography-mass spectrometry. Associations with in-hospital mortality (72 events), all-cause mortality (death, 268 events) and a composite of death or rehospitalisation due to HF (death/HF, 384 events) at 1 year were examined. RESULTS: TMAO improved risk stratification for in-hospital mortality in combination with current clinical scorings (OR≥1.13, p≤0.014). TMAO tertile analyses reported a graded risk in adverse outcome within 1 year (OR≥1.61, p≤0.004) and improved outcome prediction when stratified as none, one or both biomarker(s) elevated in combination with N-terminal pro B-type natriuretic peptide (NT-proBNP) (OR≥2.15, p≤0.007). TMAO was independently predictive for death and death/HF when corrected for cardiac risk factors (HR≥1.16, p≤0.037); however, this ability was weakened when indices of renal function were included, possibly due to multicollinearity. CONCLUSIONS: TMAO contributed additional information on patient stratification for in-hospital mortality of AHF admissions using available clinical scores that include renal indices. Furthermore, elevated levels were associated with poor prognosis at 1 year and combination of TMAO and NT-proBNP provided additional prognostic information. TMAO was a univariate predictor of death and death/HF, and remained an independent predictor until adjusted for renal confounders.

Plasma growth hormone is a strong predictor of risk at 1 year in acute heart failure.

AIMS: We sought to compare the prognostic utility of growth hormone (GH) with NT-proBNP) and the ADHERE score in a large cohort of acute heart failure (HF) patients, subcategorized into HF with reduced EF <50% (HFrEF) and preserved EF ≥50% (HFpEF). METHODS AND RESULTS: GH and NTproBNP levels were measured in 537 patients (HFrEF n = 415; HFpEF n = 122) with acute HF recruited into this prospective cohort study. The main outcome measure was death or HF readmission at 1 year. GH levels were higher in both HFrEF [1.26 (0.54-2.62) vs. 0.8 (0.26-1.94) ng/mL, P < 0.001] and HFpEF [1.04 (0.48-2.92) vs. 0.53 (0.18-1.94) ng/mL, P = 0.020] patients with the outcome compared with event-free survivors. GH levels were independently predictive for the outcome at 1 year in the entire cohort [HR 1.47, 95% confidence interval (CI) 1.16-1.86, P = 0.001] and those with HFrEF (HR 1.54, 95% CI 1.19-1.99, P = 0.001) in multivariate Cox hazard analysis. GH improved risk classification as measured by continuous net reclassification improvement (NRI) when added to the ADHERE multivariate logistic model of age, sex, urea, heart rate, and systolic blood pressure, for all patients [NRI 29.6 (12.1-47.1), P = 0.001] and HFrEF NRI 21.7 (1.9-41.6), P = 0.034] patients, as well as in addition to the ADHERE model combined with NT-proBNP for all patients [NRI 25.4 (7.8-43.1), P = 0.005]. CONCLUSIONS: GH offers incremental prognostic information over the ADHERE score clinical predictors and NT-proBNP for risk stratification of acute HF patients.

The midregional portion of proadrenomedullin is an independent predictor of left ventricular mass index in hypertension.

Left ventricular hypertrophy (LVH) is a risk factor for cardiovascular disease. Elevated natriuretic peptides in LVH have spurred interest that biomarkers may play a role in screening programs. Adrenomedullin (ADM) is a 52-amino acid peptide mediating vasorelaxation, natriuresis, and diuresis. The midregional portion of proADM (MRproADM) is secreted stoichiometrically with ADM; hence, it can be used as a surrogate marker of ADM. We compared the diagnostic performance of MRproADM for the detection of LVH with N-terminal pro-B-type natriuretic peptide (NTproBNP). Two hundred fifty-three hypertensive patients were derived from a local screening study. The MRproADM and NTproBNP levels were assayed using immunoluminometric assays. The MRproADM levels were significantly elevated in patients with LVH than those without (mean [SD]: 0.73 [0.25] vs 0.59 [0.18] nmol/L, P < .001). In multivariate analyses, male sex (P < .001) and log MRproADM (P = .003) retained significance for detecting LVH. Receiver operating characteristic curve for MRproADM yielded an area under the curve of 0.71; confidence interval, 0.62-0.81; P < .001, superior to NTproBNP. An optimal cutoff value for MRproADM as an indicator of LVH was 0.50 nmol/L, with a sensitivity, specificity, and negative predictive value of 90.5%, 36.5%, and 95.1%, respectively. The high negative predictive value of the MRproADM assay allows it to be used as a rule-out test for LVH when stratifying patients into high or low risk. Patients who test positive would necessitate echocardiography, enabling better resource allocation.

Urotensin II is raised in acute myocardial infarction and low levels predict risk of adverse clinical outcome in humans.

BACKGROUND: UII is elevated in patients with heart failure; however its role in acute myocardial infarction (AMI) is unknown. We sought to compare levels of UII in patients with AMI to controls. We also compared UII to N terminal pro B type natriuretic peptide (NT-BNP) to evaluate whether levels of UII can be used to predict the risk of adverse clinical outcome (ACO). METHODS AND RESULTS: 129 patients were studied with serial blood measurements and echocardiogram during their index admission. Plasma concentration of median UII was significantly elevated in AMI compared to controls (median 1.40 vs. 0.42 fmol/ml p<0.012). Over the median follow up of 102 days (range 0-189) there were 14 deaths and 14 readmissions with AMI or heart failure. Using a Cox proportional hazards model the only independent predictors of ACO were UII (OR 0.29, p=0.046) and NT-BNP (OR 4.78, p=0.012) between 73 and 96 h. The Kaplan-Meier survival curve revealed a significantly better clinical outcome in patients with UII above the median compared with UII below the median. CONCLUSIONS: UII levels are raised in AMI and is an independent predictor of ACO. Patients with a poor outcome mount a lower UII response suggesting a possible cardioprotective role for this peptide.