Cardiovascular magnetic resonance imaging and spectroscopy in clinical long-COVID-19 syndrome: a prospective case-control study.

BACKGROUND: The underlying pathophysiology of post-coronavirus disease 2019 (long-COVID-19) syndrome remains unknown, but increased cardiometabolic demand and state of mitochondrial dysfunction have emerged as candidate mechanisms. Cardiovascular magnetic resonance (CMR) provides insight into pathophysiological mechanisms underlying cardiovascular disease and 31-phosphorus CMR spectroscopy (31P-CMRS) allows non-invasive assessment of the myocardial energetic state. The main aim of the study was to assess whether long COVID-19 syndrome is associated with abnormalities of myocardial structure, function, perfusion and energy metabolism. METHODS: Prospective case-control study. A total of 20 patients with a clinical diagnosis of long COVID-19 syndrome (seropositive) and no prior underlying cardiovascular disease (CVD) and 10 matching healthy controls underwent 31P-CMRS and CMR at 3T at a single time point. All patients had been symptomatic with acute COVID-19, but none required hospital admission. RESULTS: Between the long COVID-19 syndrome patients and matched contemporary healthy controls there were no differences in myocardial energetics (phosphocreatine to ATP ratio), in cardiac structure (biventricular volumes), function (biventricular ejection fractions, global longitudinal strain), tissue characterization (T1 mapping and late gadolinium enhancement) or perfusion (myocardial rest and stress blood flow, myocardial perfusion reserve). One patient with long COVID-19 syndrome showed subepicardial hyperenhancement on late gadolinium enhancement imaging compatible with prior myocarditis, but no accompanying abnormality in cardiac size, function, perfusion, extracellular volume fraction, native T1, T2 or cardiac energetics. CONCLUSIONS: In this prospective case-control study, the overwhelming majority of patients with a clinical long COVID-19 syndrome with no prior CVD did not exhibit any abnormalities in myocardial energetics, structure, function, blood flow or tissue characteristics.

Acute coronary syndrome management in older adults: guidelines, temporal changes and challenges.

Advancing age is a risk factor for the development of coronary artery disease and is an important indicator of outcome after acute coronary syndrome. As the number of older adults increases, the burden of cardiovascular disease is set to grow particularly as older adults remain disadvantaged in the delivery of acute cardiac care. This article reviews the temporal changes in the provision of guideline recommended therapies for the management of acute coronary syndrome, discusses reasons for age-dependent inequalities in care and the challenges facing clinicians.

Distal Ventricular Pacing for Drug-Refractory Mid-Cavity Obstructive Hypertrophic Cardiomyopathy: A Randomized, Placebo-Controlled Trial of Personalized Pacing.

BACKGROUND: Patients with refractory, symptomatic left ventricular (LV) mid-cavity obstructive (LVMCO) hypertrophic cardiomyopathy have few therapeutic options. Right ventricular pacing is associated with modest hemodynamic and symptomatic improvement, and LV pacing pilot data suggest therapeutic potential. We hypothesized that site-specific pacing would reduce LVMCO gradients and improve symptoms. METHODS: Patients with symptomatic-drug-refractory LVMCO were recruited for a randomized, blinded trial of personalized prescription of pacing (PPoP). Multiple LV and apical right ventricular pacing sites were assessed during an invasive hemodynamic study of multisite pacing. Patient-specific pacing-site and atrioventricular delays, defining PPoP, were selected on the basis of LVMCO gradient reduction and acceptable pacing parameters. Patients were randomized to 6 months of active PPoP or backup pacing in a crossover design. The primary outcome examined invasive gradient change with best-site pacing. Secondary outcomes assessed quality of life and exercise following randomization to PPoP. RESULTS: A total of 17 patients were recruited; 16 of whom met primary end points. Baseline New York Heart Association was 3±0.6, despite optimal medical therapy. Hemodynamic effects were assessed during pacing at the right ventricular apex and at a mean of 8 LV sites. The gradients in all 16 patients fell with pacing, with maximum gradient reduction achieved via LV pacing in 14 (88%) patients and right ventricular apex in 2. The mean baseline gradient of 80±29 mm Hg fell to 31±21 mm Hg with best-site pacing, a 60% reduction (P<0.0001). One cardiac vein perforation occurred in 1 case, and 15 subjects entered crossover; 2 withdrawals occurred during crossover. Of the 13 completing crossover, 9 (69%) chose active pacing in PPoP configuration as preferred setting. PPoP was associated with improved 6-minute walking test performance (328.5±99.9 versus 285.8±105.5 m; P=0.018); other outcome measures also indicated benefit with PPoP. CONCLUSIONS: In a randomized placebo-controlled trial, PPoP reduces obstruction and improves exercise performance in severely symptomatic patients with LVMCO. REGISTRATION: URL: https://clinicaltrials.gov/study; Unique Identifier: NCT03450252.

Acute Myocarditis Mimicking Hypertrophic Cardiomyopathy in Marfan Syndrome and Morphologically Abnormal Mitral Valve.

A 40-year-old man with Marfan syndrome presented with chest pain and troponin elevation. Urgent echocardiography was suggestive of hypertrophic cardiomyopathy, but cardiovascular magnetic resonance identified features of acute myocarditis. Repeated imaging 4 months later showed resolution of septal thickness, confirming acute myocarditis. (Level of Difficulty: Intermediate.).

HEART rate variability biofeedback for long COVID symptoms (HEARTLOC): protocol for a feasibility study.

INTRODUCTION: Long COVID (LC), also known as post-COVID-19 syndrome, refers to symptoms persisting 12 weeks after COVID-19 infection. It affects up to one in seven people contracting the illness and causes a wide range of symptoms, including fatigue, breathlessness, palpitations, dizziness, pain and brain fog. Many of these symptoms can be linked to dysautonomia or dysregulation of the autonomic nervous system after SARS-CoV2 infection. This study aims to test the feasibility and estimate the efficacy, of the heart rate variability biofeedback (HRV-B) technique via a standardised slow diaphragmatic breathing programme in individuals with LC. METHODS AND ANALYSIS: 30 adult LC patients with symptoms of palpitations or dizziness and an abnormal NASA Lean Test will be selected from a specialist Long COVID rehabilitation service. They will undergo a 4-week HRV-B intervention using a Polar chest strap device linked to the Elite HRV phone application while undertaking the breathing exercise technique for two 10 min periods everyday for at least 5 days a week. Quantitative data will be gathered during the study period using: HRV data from the chest strap and wrist-worn Fitbit, the modified COVID-19 Yorkshire Rehabilitation Scale, Composite Autonomic Symptom Score, WHO Disability Assessment Schedule and EQ-5D-5L health-related quality of life measures. Qualitative feedback on user experience and feasibility of using the technology in a home setting will also be gathered. Standard statistical tests for correlation and significant difference will be used to analyse the quantitate data. ETHICS AND DISSEMINATION: The study has received ethical approval from Health Research Authority (HRA) Leicester South Research Ethics Committee (21/EM/0271). Dissemination plans include academic and lay publications. TRIAL REGISTRATION NUMBER: NCT05228665.

Association of heart failure and its comorbidities with loss of life expectancy.

OBJECTIVE: Estimating survival can aid care planning, but the use of absolute survival projections can be challenging for patients and clinicians to contextualise. We aimed to define how heart failure and its major comorbidities contribute to loss of actuarially predicted life expectancy. METHODS: We conducted an observational cohort study of 1794 adults with stable chronic heart failure and reduced left ventricular ejection fraction, recruited from cardiology outpatient departments of four UK hospitals. Data from an 11-year maximum (5-year median) follow-up period (999 deaths) were used to define how heart failure and its major comorbidities impact on survival, relative to an age-sex matched control UK population, using a relative survival framework. RESULTS: After 10 years, mortality in the reference control population was 29%. In people with heart failure, this increased by an additional 37% (95% CI 34% to 40%), equating to an additional 2.2 years of lost life or a 2.4-fold (2.2-2.5) excess loss of life. This excess was greater in men than women (2.4 years (2.2-2.7) vs 1.6 years (1.2-2.0); p<0.001). In patients without major comorbidity, men still experienced excess loss of life, while women experienced less and were non-significantly different from the reference population (1 year (0.6-1.5) vs 0.4 years (-0.3 to 1); p<0.001). Accrual of comorbidity was associated with substantial increases in excess lost life, particularly for diabetes, chronic kidney and lung disease. CONCLUSIONS: Comorbidity accounts for the majority of lost life expectancy in people with heart failure. Women, but not men, without comorbidity experience survival close to reference controls.

Risk stratification for ST segment elevation myocardial infarction in the era of primary percutaneous coronary intervention.

Acute coronary syndromes presenting with ST elevation are usually treated with emergency reperfusion/revascularisation therapy. In contrast current evidence and national guidelines recommend risk stratification for non ST segment elevation myocardial infarction (NSTEMI) with the decision on revascularisation dependent on perceived clinical risk. Risk stratification for STEMI has no recommendation. Statistical risk scoring techniques in NSTEMI have been demonstrated to improve outcomes however their uptake has been poor perhaps due to questions over their discrimination and concern for application to individuals who may not have been adequately represented in clinical trials. STEMI is perceived to carry sufficient risk to warrant emergency coronary intervention [by primary percutaneous coronary intervention (PPCI)] even if this results in a delay to reperfusion with immediate thrombolysis. Immediate thrombolysis may be as effective in patients presenting early, or at low risk, but physicians are poor at assessing clinical and procedural risks and currently are not required to consider this. Inadequate data on risk stratification in STEMI inhibits the option of immediate fibrinolysis, which may be cost-effective. Currently the mode of reperfusion for STEMI defaults to emergency angiography and percutaneous coronary intervention ignoring alternative strategies. This review article examines the current risk scores and evidence base for risk stratification for STEMI patients. The requirements for an ideal STEMI risk score are discussed.

Ongoing requirement for pacing post-transcatheter aortic valve implantation and surgical aortic valve replacement.

OBJECTIVES: Transcatheter aortic valve implantation (TAVI) is an established intervention for aortic stenosis. While it is known that the requirement for permanent pacing is higher following CoreValve (Medtronic, Inc., Minneapolis, MN, USA) TAVI than after surgical aortic valve replacement (SAVR), it remains uncertain whether pacing is required in the medium-to-long term. We hypothesized that complete heart block following TAVI is more likely to resolve than that following SAVR. METHODS: A retrospective analysis of prospectively collated data on 528 patients undergoing TAVI or SAVR from May 2008 to December 2010 at a cardiac tertiary referral hospital. Demographic data, timing and indication for pacing post-procedure plus follow-up were recorded. Paced patients were compared and analysed by existing initial indication for pacing. RESULTS: In total, 31 (5.9%) patients received a pacemaker, and there were limited differences between not paced and paced patient characteristics by procedure type. Of these, a greater proportion were implanted post-TAVI compared with SAVR (17 vs 3.2%, P<0.001). The mean time to pacemaker follow-up for TAVI and SAVR was 234 and 188 days, P=0.32, respectively. Fewer patients compared with pacing indication remained in complete heart block at latest follow-up for TAVI (76.5 vs 33.3%, P=0.02) and SAVR (92.9 vs 58.3%, P=0.04). Although, there was a trend towards a greater magnitude of TAVI patients regaining atrioventricular nodal conduction, this did not differ significantly from that seen in SAVR patients. CONCLUSIONS: In keeping with previous reports, this single-centre experience demonstrates that patients undergoing TAVI have higher rates of pacemaker implantation than those following SAVR. However, pacing indication in the short-to-medium term may not persist for all paced patients post-TAVI and -SAVR with the suggestion that a significant proportion recover atrioventricular conduction, which tended to be greatest in TAVI paced patients.

Evaluation of the NICE mini-GRACE risk scores for acute myocardial infarction using the Myocardial Ischaemia National Audit Project (MINAP) 2003-2009: National Institute for Cardiovascular Outcomes Research (NICOR).

OBJECTIVE: To evaluate the performance of the National Institute for Health and Clinical Excellence (NICE) mini-Global Registry of Acute Coronary Events (GRACE) (MG) and adjusted mini-GRACE (AMG) risk scores. DESIGN: Retrospective observational study. SETTING: 215 acute hospitals in England and Wales. PATIENTS: 137 084 patients discharged from hospital with a diagnosis of acute myocardial infarction (AMI) between 2003 and 2009, as recorded in the Myocardial Ischaemia National Audit Project (MINAP). MAIN OUTCOME MEASURES: Model performance indices of calibration accuracy, discriminative and explanatory performance, including net reclassification index (NRI) and integrated discrimination improvement. RESULTS: Of 495 263 index patients hospitalised with AMI, there were 53 196 ST elevation myocardial infarction and 83 888 non-ST elevation myocardial infarction (NSTEMI) (27.7%) cases with complete data for all AMG variables. For AMI, AMG calibration was better than MG calibration (Hosmer-Lemeshow goodness of fit test: p=0.33 vs p<0.05). MG and AMG predictive accuracy and discriminative ability were good (Brier score: 0.10 vs 0.09; C statistic: 0.82 and 0.84, respectively). The NRI of AMG over MG was 8.1% (p<0.05). Model performance was reduced in patients with NSTEMI, chronic heart failure, chronic renal failure and in patients aged ≥85 years. CONCLUSIONS: The AMG and MG risk scores, utilised by NICE, demonstrated good performance across a range of indices using MINAP data, but performed less well in higher risk subgroups. Although indices were better for AMG, its application may be constrained by missing predictors.

An assessment of composite measures of hospital performance and associated mortality for patients with acute myocardial infarction. Analysis of individual hospital performance and outcome for the National Institute for Cardiovascular Outcomes Research (NICOR).

AIM: To investigate whether a hospital-specific opportunity-based composite score (OBCS) was associated with mortality in 136,392 patients with acute myocardial infarction (AMI) using data from the Myocardial Ischaemia National Audit Project (MINAP) 2008-2009. METHODS AND RESULTS: For 199 hospitals a multidimensional hospital OBCS was calculated on the number of times that aspirin, thienopyridine, angiotensin-converting enzyme inhibitor (ACEi), statin, ß-blocker, and referral for cardiac rehabilitation was given to individual patients, divided by the overall number of opportunities that hospitals had to give that care. OBCS and its six components were compared using funnel plots. Associations between OBCS performance and 30-day and 6-month all-cause mortality were quantified using mixed-effects regression analysis. Median hospital OBCS was 95.3% (range 75.8-100%). By OBCS, 24.1% of hospitals were below funnel plot 99.8% CI, compared to aspirin (11.1%), thienopyridine (15.1%), ß-blockers (14.7%), ACEi (19.1%), statins (12.1%), and cardiac rehabilitation (17.6%) on discharge. Mortality (95% CI) decreased with increasing hospital OBCS quartile at 30 days [Q1, 2.25% (2.07-2.43%) vs. Q4, 1.40% (1.25-1.56%)] and 6 months [Q1, 7.93% (7.61-8.25%) vs. Q4, 5.53% (5.22-5.83%)]. Hospital OBCS quartile was inversely associated with adjusted 30-day and 6-month mortality [OR (95% CI), 0.87 (0.80-0.94) and 0.92 (0.88-0.96), respectively] and persisted after adjustment for coronary artery catheterization [0.89 (0.82-0.96) and 0.95 (0.91-0.98), respectively]. CONCLUSIONS: Multidimensional hospital OBCS in AMI survivors are high, discriminate hospital performance more readily than single performance indicators, and significantly inversely predict early and longer-term mortality.

Acute coronary syndromes: an old age problem.

The increasing population in older age will lead to greater numbers of them presenting with acute coronary syndromes (ACS). This has implications on global healthcare resources and necessitates better management and selection for evidenced-based therapies. The elderly are a high risk group with more significant treatment benefits than younger ACS. Nevertheless, age related inequalities in ACS care are recognised and persist. This discrepancy in care, to some extent, is explained by the higher frequency of atypical and delayed presentations in the elderly, and less diagnostic electrocardiograms at presentation, potentiating a delay in ACS diagnosis. Under estimation of mortality risk in the elderly due to limited consideration for physiological frailty, co-morbidity, cognitive/psychological impairment and physical disability, less input by cardiology specialists and lack of randomised, controlled trials data to guide management in the elderly may further confound the inequality of care. While these inequalities exist, there remains a substantial opportunity to improve age related ACS outcomes. The selection of elderly patients for specific therapies and medication regimens are unanswered. There is a growing need for randomised, controlled trial data to be more representative of the population and enroll those of advanced age with co-morbidity. A lack of reporting of adverse events, such as renal impairment post coronary angiography, in the elderly further limit risk benefit decisions. Substantial improvements in care of elderly ACS patients are required and should be advocated. Ultimately, these improvements are likely to lead to better outcomes post ACS. However, the improvement in outcome is not infinite and will be limited by non-modifiable factors of age-related risk.