Health-related quality of life in cardiac sarcoidosis: a systematic review.

People living with cardiac sarcoidosis (CS) are likely to have worse clinical outcomes and greater impairment on health-related quality of life (HRQoL) than other sarcoidosis manifestations. CS can result in a constellation of intrusive symptoms (such as palpitations, dizziness, syncope/pre-syncope, chest pain, dyspnoea, orthopnoea, or peripheral oedema) and/or life-threatening episodes, requiring consideration of invasive cardiac procedures for diagnosis and for the management of acute events. Additionally, the presence of multisystemic involvement and persistent non-specific sarcoidosis symptoms negatively affect HRQoL. A systematic review was undertaken to explore the impact of CS on HRQoL in adults with CS. Multiple bibliographic databases were searched for studies with HRQoL as primary or secondary outcomes in CS (PROSPERO registration: CRD42019119752). Data extraction and quality assessments were undertaken independently by two authors. From the initial 1609 identified records, only 11 studies included CS patients but none specifically reported HRQoL scores for CS patients. The average representation of CS patients was 14.5% within these cohorts (range 2-22%). The majority (73%) was conducted in single-centre tertiary care settings, and only one study (9%) included longitudinal HRQoL data. CS patients were among those sarcoidosis patients with impaired HRQoL and worse outcomes, requiring higher doses of sarcoidosis-specific therapy which contribute to further deterioration of HRQoL. Sarcoidosis studies do not incorporate stratified HRQoL scores for CS patients. While there is a need for longitudinal and multicentre studies assessing HRQoL outcomes in CS cohorts, the development of CS-specific tools is also needed.

Acute Myocarditis Associated With Desmosomal Gene Variants.

BACKGROUND: The risk of adverse cardiovascular events in patients with acute myocarditis (AM) and desmosomal gene variants (DGV) remains unknown. OBJECTIVES: The purpose of this study was to ascertain the risk of death, ventricular arrhythmias, recurrent myocarditis, and heart failure (main endpoint) in patients with AM and pathogenic or likely pathogenetic DGV. METHODS: In a retrospective international study from 23 hospitals, 97 patients were included: 36 with AM and DGV (DGV[+]), 25 with AM and negative gene testing (DGV[-]), and 36 with AM without genetics testing. All patients had troponin elevation plus findings consistent with AM on histology or at cardiac magnetic resonance (CMR). In 86 patients, CMR changes in function and structure were re-assessed at follow-up. RESULTS: In the DGV(+) AM group (88.9% DSP variants), median age was 24 years, 91.7% presented with chest pain, and median left ventricular ejection fraction (LVEF) was 56% on CMR (P = NS vs the other 2 groups). Kaplan-Meier curves demonstrated a higher risk of the main endpoint in DGV(+) AM compared with DGV(-) and without genetics testing patients (62.3% vs 17.5% vs 5.3% at 5 years, respectively; P < 0.0001), driven by myocarditis recurrence and ventricular arrhythmias. At follow-up CMR, a higher number of late gadolinium enhanced segments was found in DGV(+) AM. CONCLUSIONS: Patients with AM and evidence of DGV have a higher incidence of adverse cardiovascular events compared with patients with AM without DGV. Further prospective studies are needed to ascertain if genetic testing might improve risk stratification of patients with AM who are considered at low risk.

Evidence to support magnetic resonance conditional labelling of all pacemaker and defibrillator leads in patients with cardiac implantable electronic devices.

AIMS: Many cardiac pacemakers and defibrillators are not approved by regulators for magnetic resonance imaging (MRI). Even following generator exchange to an approved magnetic resonance (MR)-conditional model, many systems remain classified 'non-MR conditional' due to the leads. This classification makes patient access to MRI challenging, but there is no evidence of increased clinical risk. We compared the effect of MRI on non-MR conditional and MR-conditional pacemaker and defibrillator leads. METHODS AND RESULTS: Patients undergoing clinical 1.5T MRI with pacemakers and defibrillators in three centres over 5 years were included. Magnetic resonance imaging protocols were similar for MR-conditional and non-MR conditional systems. Devices were interrogated pre- and immediately post-scan, and at follow-up, and adverse clinical events recorded. Lead parameter changes peri-scan were stratified by MR-conditional labelling. A total of 1148 MRI examinations were performed in 970 patients (54% non-MR conditional systems, 39% defibrillators, 15% pacing-dependent) with 2268 leads. There were no lead-related adverse clinical events, and no clinically significant immediate or late lead parameter changes following MRI in either MR-conditional or non-MR conditional leads. Small reductions in atrial and right ventricular sensed amplitudes and impedances were similar between groups, with no difference in the proportion of leads with parameter changes greater than pre-defined thresholds (7.1%, 95% confidence interval: 6.1-8.3). CONCLUSIONS: There was no increased risk of MRI in patients with non-MR conditional pacemaker or defibrillator leads when following recommended protocols. Standardizing MR conditions for all leads would significantly improve access to MRI by enabling patients to be scanned in non-specialist centres, with no discernible incremental risk.

The Safety and Feasibility of Transitioning From Transfemoral to Transradial Access Left Ventricular Endomyocardial Biopsy.

BACKGROUND: Left ventricular endomyocardial biopsy (LVEMB) is commonly performed via the transfemoral route. Radial access may help reduce vascular access complications, but there are few data on the safety and feasibility of transradial LVEMB. OBJECTIVE: Describe the safety and feasibility of transitioning from transfemoral to transradial access LVEMB. METHODS: This is a single-center, prospective, observational cohort study. Fifty procedures in 49 patients were included, 25 (50%) via the femoral route and 25 (50%) via the radial route. RESULTS: The cohort had a mean age of 47 ± 13 years and the most common indication for LVEMB was myocarditis. From June 2015 until September 2016, all procedures (n = 21) were performed via the femoral approach; thenceforth, there was a gradual transition to the radial approach. More tissue samples were obtained when the procedure was performed via the femoral approach (P<.01). The minimum sampling target of 3 specimens was not met in 4 patients (16%) via the radial approach and in 1 patient (4%) via the femoral approach. Complications occurred in 3/25 transradial procedures (12%; 2 cardiac perforations and 1 forearm hematoma) and 3/25 transfemoral procedures (12%; 1 cardiac perforation, 1 femoral artery pseudoaneurysm, and 1 ventricular fibrillation). Cardiac perforations via the transradial approach occurred during the early transition period. There were no deaths. CONCLUSIONS: Transradial LVEMB is feasible, with a similar complication profile to femoral procedures, but associated with a smaller number of specimens. Transitioning from transfemoral to transradial procedures may initially be associated with a higher risk of complications and potentially a lower diagnostic yield.

Clinical impact of cardiovascular magnetic resonance with optimized myocardial scar detection in patients with cardiac implantable devices.

BACKGROUND: Myocardial scar assessment using late gadolinium enhancement Cardiovascular Magnetic Resonance (LGE CMR) is commonly indicated for patients with cardiac implantable electronic devices (CIEDs), however metal artifact can degrade images. We evaluated the clinical impact of LGE CMR incorporating a device-dependent metal artifact reduction strategy in patients with CIEDs. METHODS: 136 CMR studies were performed in 133 consecutive patients (age 56 ±â€¯19 years, 69% male) with CIEDs (22% implantable loop recorders [ILRs], 40% permanent pacemakers [PPMs], 38% implantable cardioverter defibrillators [ICDs]; 42% non-MRI conditional) over 2 years, without complication. LGE imaging was tailored to the CIED, using a wideband sequence for left-sided PPMs and ICDs and conventional sequences for ILRs and right-sided PPMs, scoring segmental artifact. Diagnostic utility and impact on clinical management were scored by consensus of experts. RESULTS: CMR provided unexpected diagnoses in 22 (16%) and changed management in 113 (83%) patients. Myocardial scar was present in 92 (68%), with other abnormalities detected in another 13%. Using conventional LGE, 43 (32%) studies were non-diagnostic (79% of defibrillators) compared to 0% using wideband LGE imaging. Wideband LGE results changed clinical management in an additional 39 (75%) defibrillator patients and 10 (19%) pacemaker patients when compared to imaging with conventional LGE sequences. CONCLUSION: The clinical yield from CMR using optimized LGE sequences in patients with CIEDs is high with no demonstrated clinical risk. A device-dependent LGE imaging strategy using wideband LGE is needed to achieve clinical utility especially in ICD recipients.

Prevalence of 18F-fluorodeoxyglucose positron emission tomography abnormalities in patients with arrhythmogenic right ventricular cardiomyopathy.

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a heritable heart muscle disease that causes sudden cardiac death in the young. Inflammatory myocardial infiltrates have been described at autopsy and on biopsy, but there are few data on the presence of myocarditis in living patients with ARVC using non-invasive imaging techniques. FDG-PET is a validated technique for detecting myocardial inflammation in clinically suspected myocarditis. We aimed to determine the prevalence of myocardial inflammation in patients with ARVC using 18F-fluorodeoxyglucose positron emission tomography (FDG-PET). METHODS AND RESULTS: We performed a retrospective analysis of a single centre cohort of patients with ARVC referred for FDG-PET scans between 2012 and 2017 for investigation of symptoms or suspected device infection. Sixteen patients (12 male; age 42 ±â€¯13 years) with a definite diagnosis of ARVC were identified. Seven had positive FDG-PET scans, two of whom had cardiac sarcoidosis on endomyocardial biopsy. Of the remaining five, two carried pathogenic desmoplakin mutations. FDG uptake was found in the left ventricular myocardium in all cases. One patient also had right ventricular uptake. CONCLUSION: In this exploratory study, we show that some patients with ARVC have evidence for myocardial inflammation on FDG-PET, suggesting that myocarditis plays a role in disease pathogenesis.

Percutaneous extraction of an embolized progesterone contraceptive implant from the pulmonary artery.

The Nexplanon® implant is a commonly used radiopaque contraceptive device that contains progestogen associated with an ethylene vinyl-acetate copolymer resulting in a slow release of the active hormonal ingredient. It is inserted into the subdermal connective tissue and provides contraceptive efficacy for up to 3 years. Device removal for clinical, personal or device "end-of-life span" reasons is straightforward. In rare cases, implant migration can occur locally within centimeters of the insertion site. Distant device embolization is extremely rare and can result in complications including chest pain, dyspnoea, pneumothorax and thrombosis or prevent conception until the active ingredient is depleted. We present one such case, where a Nexplanon® implant embolized into the pulmonary artery of a young female patient. We describe the initial "missed" diagnosis of embolized device on a chest radiograph and subsequent successful percutaneous removal once distant embolization was diagnosed.

Diagnostic accuracy and prognostic value of simultaneous hybrid 18F-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging in cardiac sarcoidosis.

Aims: Cardiac death is the leading cause of mortality in patients with sarcoidosis, yet cardiac involvement often remains undetected. Cardiovascular magnetic resonance imaging (CMR) and 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) have been used to diagnose cardiac sarcoidosis (CS) yet never simultaneously in a cohort. This study sought to assess the diagnostic and prognostic utility of simultaneous hybrid cardiac PET/MR. Methods and results: Fifty-one consecutive patients with suspected CS (age 50 ± 13 years, 31 males) underwent simultaneous PET/MR following a high-fat/low-carbohydrate diet and 12-h fast. Blinded image analysis of FDG uptake and late gadolinium enhancement (LGE) was performed using the American Heart Association (AHA) 16-segment model. The sensitivity and specificity of PET/MR for diagnosing CS was estimated using the Japanese Ministry of Health and Welfare guidelines. The primary endpoint was a composite of death, aborted sudden cardiac death, sustained ventricular arrhythmia, complete heart block, and hospital admission with decompensated heart failure. The secondary endpoints were a fall in left ventricular ejection fraction (LVEF) >10%, non-sustained ventricular tachycardia and other cardiac-related hospital admission. The prevalence of CS was 65% (n = 33). The sensitivity of PET and CMR alone for detecting CS was 0.85 and 0.82, respectively. Hybrid PET/MR was superior for detecting CS with sensitivity, specificity, positive, and negative predictive values of 0.94, 0.44, 0.76, and 0.80, respectively. There was poor inter-modality agreement for the location of cardiac abnormalities (k = 0.02). Over the median follow-up of 2.2 years, there were 18 (35%) adverse events. Cardiac RV PET abnormalities and presence of LGE were independent predictors of adverse events. Abnormalities found on both PET and magnetic resonance imaging was the strongest predictor of major adverse cardiac events. Conclusion: Simultaneous PET/MR is an accurate method for diagnosing CS. FDG-PET and CMR combined offers complementary information on disease pathophysiology. The presence of LGE and FDG uptake on PET/MR identifies patients at higher risk of adverse events. PET and CMR should therefore be considered in the assessment of disease presence, stage, and prognosis in CS.

Ineffective and prolonged apical contraction is associated with chest pain and ischaemia in apical hypertrophic cardiomyopathy.

OBJECTIVES: To investigate the hypothesis that persistence of apical contraction into diastole is linked to reduced myocardial perfusion and chest pain. BACKGROUND: Apical hypertrophic cardiomyopathy (HCM) is defined by left ventricular (LV) hypertrophy predominantly of the apex. Hyperdynamic contractility resulting in obliteration of the apical cavity is often present. Apical HCM can lead to drug-refractory chest pain. METHODS: We retrospectively studied 126 subjects; 76 with apical HCM and 50 controls (31 with asymmetrical septal hypertrophy (ASH) and 19 with non-cardiac chest pain and culprit free angiograms and structurally normal hearts). Perfusion cardiac magnetic resonance imaging (CMR) scans were assessed for myocardial perfusion reserve index (MPRi), late gadolinium enhancement (LGE), LV volumes (muscle and cavity) and regional contractile persistence (apex, mid and basal LV). RESULTS: In apical HCM, apical MPRi was lower than in normal and ASH controls (p<0.05). In apical HCM, duration of contractile persistence was associated with lower MPRi (p<0.01) and chest pain (p<0.05). In multivariate regression, contractile persistence was independently associated with chest pain (p<0.01) and reduced MPRi (p<0.001). CONCLUSION: In apical HCM, regional contractile persistence is associated with impaired myocardial perfusion and chest pain. As apical myocardium makes limited contributions to stroke volume, apical contractility is also largely ineffective. Interventions to reduce apical contraction and/or muscle mass are potential therapies for improving symptoms without reducing cardiac output.

International External Validation Study of the 2014 European Society of Cardiology Guidelines on Sudden Cardiac Death Prevention in Hypertrophic Cardiomyopathy (EVIDENCE-HCM).

BACKGROUND: Identification of people with hypertrophic cardiomyopathy (HCM) who are at risk of sudden cardiac death (SCD) and require a prophylactic implantable cardioverter defibrillator is challenging. In 2014, the European Society of Cardiology proposed a new risk stratification method based on a risk prediction model (HCM Risk-SCD) that estimates the 5-year risk of SCD. The aim was to externally validate the 2014 European Society of Cardiology recommendations in a geographically diverse cohort of patients recruited from the United States, Europe, the Middle East, and Asia. METHODS: This was an observational, retrospective, longitudinal cohort study. RESULTS: The cohort consisted of 3703 patients. Seventy three (2%) patients reached the SCD end point within 5 years of follow-up (5-year incidence, 2.4% [95% confidence interval {CI}, 1.9-3.0]). The validation study revealed a calibration slope of 1.02 (95% CI, 0.93-1.12), C-index of 0.70 (95% CI, 0.68-0.72), and D-statistic of 1.17 (95% CI, 1.05-1.29). In a complete case analysis (n= 2147; 44 SCD end points at 5 years), patients with a predicted 5-year risk of <4% (n=1524; 71%) had an observed 5-year SCD incidence of 1.4% (95% CI, 0.8-2.2); patients with a predicted risk of ≥6% (n=297; 14%) had an observed SCD incidence of 8.9% (95% CI, 5.96-13.1) at 5 years. For every 13 (297/23) implantable cardioverter defibrillator implantations in patients with an estimated 5-year SCD risk ≥6%, 1 patient can potentially be saved from SCD. CONCLUSIONS: This study confirms that the HCM Risk-SCD model provides accurate prognostic information that can be used to target implantable cardioverter defibrillator therapy in patients at the highest risk of SCD.

Doppler echocardiography underestimates the prevalence and magnitude of mid-cavity obstruction in patients with symptomatic hypertrophic cardiomyopathy.

OBJECTIVES: To evaluate utility of Doppler echocardiography in the assessment of left ventricular (LV) mid-cavity obstructive (LVMCO) hypertrophic cardiomyopathy (HCM). BACKGROUND: LVMCO is a relatively under-diagnosed complication of HCM and may occur alone or in combination with LV outflow tract obstruction (LVOTO). Identifying and quantifying LVMCO and differentiating it from LVOTO has important implications for patient management. We aimed to assess diagnostic performance of Doppler echocardiography in the assessment of suspected LV obstruction. METHODS: Forty symptomatic HCM patients with suspected obstruction underwent cardiac catheterization, and comparison of location and magnitude of Doppler derived gradients with synchronous invasive measurements (reference standard), at rest and isoprenaline stress (IS). RESULTS: Doppler's diagnostic accuracy for any obstruction (≥30 mmHg) in this cohort was 75% with false positive and false negative rates of 2.5 and 22.5%, respectively. During subanalysis, Doppler's diagnostic accuracy for isolated LVOTO in this selected cohort is 83% with false positive and false negative rates of 4 and 12.5%, respectively. For LVMCO, the accuracy is only 50%, with false positive and false negative rates of 10 and 40%, respectively. Doppler gradients for isolated LVOTO were similar to invasive: 85 ± 51 and 87 ± 35 mmHg, respectively (P = 0.77). Doppler gradients in LVMCO were consistently lower than invasive: 45 ± 38 and 81 ± 31 mmHg, respectively (P = 0.0002). Mid-systolic flow cessation and/or contamination of spectral signals were identified as causes of Doppler-derived inaccuracies. CONCLUSIONS: Doppler echocardiography under-diagnoses and underestimates severity of LVMCO in symptomatic HCM patients. Recognition of abrupt mid-systolic flow cessation and invasive measurements may improve detection of LVMCO in HCM.

A 10-year prognostic model for patients with suspected angina attending a chest pain clinic.

BACKGROUND AND OBJECTIVE: Diagnostic models used in the management of suspected angina provide no explicit information about prognosis. We present a new prognostic model of 10-year coronary mortality in patients presenting for the first time with suspected angina to complement the Diamond-Forrester diagnostic model of disease probability. METHODS AND RESULTS: A multicentre cohort of 8762 patients with suspected angina was followed up for a median of 10 years during which 233 coronary deaths were observed. Developmental (n=4412) and validation (n=4350) prognostic models based on clinical data available at first presentation showed good performance with close agreement and the final model utilised all 8762 patients to maximise power. The prognostic model showed strong associations with coronary mortality for age, sex, chest pain typicality, smoking status, diabetes, pulse rate, and ECG findings. Model discrimination was good (C statistic 0.83), patients in the highest risk quarter accounting for 173 coronary deaths (10-year risk of death: 8.7%) compared with a total of 60 deaths in the three lower risk quarters. When the model was simplified to incorporate only Diamond-Forrester factors (age, sex and character of symptoms) it underestimated coronary mortality risk, particularly in patients with reversible risk factors. CONCLUSIONS: For the first time in patients with suspected angina, a prognostic model is presented based on simple clinical factors available at the initial cardiological assessment. The model discriminated powerfully between patients at high risk and lower risk of coronary death during 10-year follow-up. Clinical utility was reflected in the prognostic value it added to the updated Diamond-Forrester diagnostic model of disease probability.

Cor triatriatum and hypertrophic cardiomyopathy.

: Cor triatriatum is a rare congenital anomaly known to be associated with other inherited heart diseases. We present a nonrestrictive cor triatriatum sinistrum associated with hypertrophic cardiomyopathy to illustrate how different multimodality noninvasive imaging techniques complement each other and can help with the diagnosis. To the best of our knowledge, this coexistence has not been previously reported.

Atypical chest pain in diabetic patients with suspected stable angina: impact on diagnosis and coronary outcomes.

AIMS: Silent myocardial ischaemia occurs commonly in diabetes. Whether altered perception of ischaemia also predisposes to atypical presentations with under-diagnosis of coronary disease is not known. To determine whether (i) patients with diabetes diagnosed with angina are more likely to report atypical symptoms compared with patients without diabetes, and (ii) atypical symptoms in patients with diabetes cause angina to go unrecognized, increasing the risk of coronary events. METHODS AND RESULTS: Prospective, multicentre cohort study of 8662 ambulatory patients with suspected angina, of whom 906 had diabetes. We recorded detailed chest pain descriptors and fatal and non-fatal coronary events over a median of 3.08 years of follow-up. Proportionately more patients with than without diabetes received a diagnosis of angina (42.7 vs. 25.1%). Among patients with diabetes diagnosed with angina, a greater proportion had atypical chest pain compared with patients without diabetes (21.0 vs. 11.3%), but the hazard of fatal and non-fatal coronary events was similar. However, among patients diagnosed with non-cardiac chest pain, those with diabetes-most of whom had atypical symptoms-remained at greater risk of coronary events [2.29 (95% CI 1.54, 3.41)] and all-cause mortality [1.67 (95% confidence interval, CI 1.04, 2.69)] compared with non-diabetic patients. CONCLUSION: Patients with diabetes and atypical symptoms are nearly twice as likely to be diagnosed with angina compared with non-diabetic patients. Those diagnosed with non-cardiac pain are at increased risk of coronary events. Our study emphasizes the need for more intensive investigation of diabetic patients with chest pain, particularly those presenting with atypical symptoms.