Polygenic risk score adds to a clinical risk score in the prediction of cardiovascular disease in a clinical setting.

BACKGROUND AND AIMS: A cardiovascular disease polygenic risk score (CVD-PRS) can stratify individuals into different categories of cardiovascular risk, but whether the addition of a CVD-PRS to clinical risk scores improves the identification of individuals at increased risk in a real-world clinical setting is unknown. METHODS: The Genetics and the Vascular Health Check Study (GENVASC) was embedded within the UK National Health Service Health Check (NHSHC) programme which invites individuals between 40-74 years of age without known CVD to attend an assessment in a UK general practice where CVD risk factors are measured and a CVD risk score (QRISK2) is calculated. Between 2012-2020, 44,141 individuals (55.7% females, 15.8% non-white) who attended an NHSHC in 147 participating practices across two counties in England were recruited and followed. When 195 individuals (cases) had suffered a major CVD event (CVD death, myocardial infarction or acute coronary syndrome, coronary revascularisation, stroke), 396 propensity-matched controls with a similar risk profile were identified, and a nested case-control genetic study undertaken to see if the addition of a CVD-PRS to QRISK2 in the form of an integrated risk tool (IRT) combined with QRISK2 would have identified more individuals at the time of their NHSHC as at high risk (QRISK2 10-year CVD risk of ≥10%), compared with QRISK2 alone. RESULTS: The distribution of the standardised CVD-PRS was significantly different in cases compared with controls (cases mean score .32; controls, -.18, P = 8.28×10-9). QRISK2 identified 61.5% (95% confidence interval [CI]: 54.3%-68.4%) of individuals who subsequently developed a major CVD event as being at high risk at their NHSHC, while the combination of QRISK2 and IRT identified 68.7% (95% CI: 61.7%-75.2%), a relative increase of 11.7% (P = 1×10-4). The odds ratio (OR) of being up-classified was 2.41 (95% CI: 1.03-5.64, P = .031) for cases compared with controls. In individuals aged 40-54 years, QRISK2 identified 26.0% (95% CI: 16.5%-37.6%) of those who developed a major CVD event, while the combination of QRISK2 and IRT identified 38.4% (95% CI: 27.2%-50.5%), indicating a stronger relative increase of 47.7% in the younger age group (P = .001). The combination of QRISK2 and IRT increased the proportion of additional cases identified similarly in women as in men, and in non-white ethnicities compared with white ethnicity. The findings were similar when the CVD-PRS was added to the atherosclerotic cardiovascular disease pooled cohort equations (ASCVD-PCE) or SCORE2 clinical scores. CONCLUSIONS: In a clinical setting, the addition of genetic information to clinical risk assessment significantly improved the identification of individuals who went on to have a major CVD event as being at high risk, especially among younger individuals. The findings provide important real-world evidence of the potential value of implementing a CVD-PRS into health systems.

Evaluating the clinical effectiveness of the NHS Health Check programme: a prospective analysis in the Genetics and Vascular Health Check (GENVASC) study.

OBJECTIVE: The aim of the study was to assess the clinical effectiveness of the national cardiovascular disease (CVD) prevention programme-National Health Service Health Check (NHSHC) in reduction of CVD risk. DESIGN: Prospective cohort study. SETTING: 147 primary care practices in Leicestershire and Northamptonshire in England, UK. PARTICIPANTS: 27 888 individuals undergoing NHSHC with a minimum of 18 months of follow-up data. OUTCOME MEASURES: The primary outcomes were NHSHC attributed detection of CVD risk factors, prescription of medications, changes in values of individual risk factors and frequency of follow-up. RESULTS: At recruitment, 18% of participants had high CVD risk (10%-20% 10-year risk) and 4% very high CVD risk (>20% 10-year risk). New diagnoses or hypertension (HTN) was made in 2.3% participants, hypercholesterolaemia in 0.25% and diabetes mellitus in 0.9%. New prescription of stains and antihypertensive medications was observed in 5.4% and 5.4% of participants, respectively. Total cholesterol was decreased on average by 0.38 mmol/L (95% CI -0.34 to -0.41) and 1.71 mmol/L (-1.48 to -1.94) in patients with initial cholesterol >5 mmol/L and >7.5 mmol/L, respectively. Systolic blood pressure was decreased on average by 2.9 mm Hg (-2.3 to -3.7), 15.7 mm Hg (-14.1 to -17.5) and 33.4 mm Hg (-29.4 to -37.7), in patients with grade 1, 2 and 3 HTN, respectively. About one out of three patients with increased CVD risk had no record of follow-up or treatment. CONCLUSIONS: Majority of patients identified with increased CVD risk through the NHSHC were followed up and received effective clinical interventions. However, one-third of high CVD risk patients had no follow-up and therefore did not receive any treatment. Our study highlights areas of focus which could improve the effectiveness of the programme. TRIAL REGISTRATION NUMBER: NCT04417387.

Reducing vitamin D requests in a primary care cohort: a quality improvement study.

BACKGROUND: Since 2000, vitamin D requests have increased 2-6 fold with no evidence of a corresponding improvement in the health of the population. The ease of vitamin D requesting may contribue to the rapid rise in its demand and, hence, pragmatic interventions to reduce vitamin D test ordering are warranted. AIM: To study the effect on vitamin D requests following a redesign of the electronic forms used in primary care. In addition, any potential harms were studied and the potential cost-savings associated with the intervention were evaluated. DESIGN & SETTING: An interventional study took place within primary care across Leicestershire, England. METHOD: The intervention was a redesign of the electronic laboratory request form for primary care practitioners across the county. Data were collected on vitamin D requests for a 6-month period prior to the change (October 2016 to March 2017) and the corresponding 6-month period post-intervention (October 2017 to March 2018), data were also collected on vitamin D, calcium, and phosphate levels. RESULTS: The number of requests for vitamin D decreased by 14 918 (36.2%) following the intervention. Changes in the median calcium and phosphate were not clinically significant. Cost-modelling suggested that if such an intervention was implemented across primary care in the UK, there would be a potential annual saving to the NHS of £38 712 606. CONCLUSION: A simple pragmatic redesign of the electronic request form for vitamin D test led to a significant reduction in vitamin D requests without any adverse effect on the quality of care.

Recordings of diaphragmatic electromyograms during cryoballoon ablation for atrial fibrillation accurately predict phrenic nerve injury.

BACKGROUND: Cryoballoon ablation has been associated with a significant incidence of phrenic nerve injury (PNI). OBJECTIVE: The purpose of this study was to evaluate whether recordings of diaphragmatic compound motor action potentials (CMAP) on a modified lead I during cryoballoon ablation can predict PNI. METHODS: Cryoballoon ablation was performed in 109 patients with atrial fibrillation (AF). During ablation of the right-sided pulmonary veins, the phrenic nerve was paced from the superior vena cava. The right and left arm electrodes from a 12-lead ECG were positioned 5 cm above the xiphoid process and 16 cm along the right costal margin. The amplitude of CMAP was recorded on lead I during ablation. RESULTS: Cryoballoon was applied 424 times in 211 right-sided veins. PNI occurred in 7 (6.4%) patients. The average CMAP amplitude did not significantly change in patients without PNI from the initial average CMAP amplitude of 0.34 ± 0.18 mV to 0.32 ± 0.17 mV (P = .58). In patients who developed PNI, there was a significant decrease in the initial average CMAP amplitude during the ablation from 0.33 ± 0.14 mV to 0.09 ± 0.05 mV (P <.001). The maximal percent change in the average CMAP amplitude in patients with PNI was higher (70% ± 10%) than in patients without PNI (7.6% ± 7%; P <.001). In any patient without PNI, the CMAP amplitude did not decrease more than 35% from baseline. CONCLUSION: Recording of CMAP amplitude on a modified lead I is reliable and could be early and sensitive method for predicting PNI in patients undergoing cryoballoon ablation for AF.

Decitabine induced transient cardiomyopathy: a case report.

CASE REPORT: A 75-yr-old gentleman, with a past medical history of diabetes mellitus and Acute Myeloid Leukemia presented to our emergency department with a chief complaint of exertional dyspnea and chest pain. A week prior to this visit, he had recieved a cycle of decitabine chemotherapy at 20 mg/metered square for ten days. This was his second cycle of decitabine. His out patient medications included megesterol, omeprazole, morphine sulfate and insulin glargine. The patient was admitted to the Coronary Care Unit for Acute Coronary Syndrome. His cardiac enzymes were elevated (peak troponin 30 ng/mL, CKMB 67.4 ng/mL). His 12 lead EKG revealed sinus tachycardia with a ventricular rate of 113, but without acute ST-T wave changes. The BNP was 259 pg/mL. A 2D echo revealed moderate diffuse hypokinesis with an EF of 35%. He subsequently underwent a left heart catheterization, which showed non-obstructive CAD. In our patient, the elevated troponins (peak troponin 30 ng/mL) and BNP were seen concomitant with the onset of cardiogenic shock. Two months ago, his 2 D echocardiogram revealed an ejection fraction of about 55%-65% with slightly increased left ventricular (LV) wall thickness. DISCUSSION: The most common adverse effects of decitabine include cytopenia, nausea, pain and erythema/nodules at the injection site. To date, there has been only one reported case of a hypomethylating agent inducing acute myocarditis. We a present a case of reversible, non-ischemic cardiomyopathy secondary to decitabine chemotherapy, which resolved after the drug was discontinued. Trials involving decitabine for the treatment of MDS reported no myocarditis. In our case, the diagnosis of transient cardiomyopathy was highly probable since the patient's troponins and echocardiogram returned to baseline after discontinuation of treatment. Also, the patient never had any further chest pain at his 6 month follow up. In this case, we believe that the elevated Troponin I levels, along with a cardiac catheterization revealing patent coronary vessels, favor our hypothesis that our patient suffered from acute myocarditis as a result of direct toxicity from decitabine chemotherapy. We doubt that there was an underlying infectious etiology, since the patient had three negative blood cultures, two negative urine cultures and a negative viral serology. Our case demonstrates that chest pains in a patient treated with hypomethylating agents should be further explored in order to rule out acute myocarditis.

Use of intracardiac echocardiography for early detection of phrenic nerve injury during cryoballoon pulmonary vein isolation.

Cryoballoon catheter ablation has recently emerged as an effective tool to achieve pulmonary vein isolation (PVI). Right-sided PVI with cryoballoon ablation has been associated with a significant incidence of phrenic nerve palsy. Multiple modalities are currently utilized to monitor phrenic nerve function during ablation. We describe a novel approach toward monitoring and diagnosing phrenic nerve palsy using intracardiac echocardiography (ICE) during cryoballoon ablation of the right pulmonary veins. This technique of monitoring has the advantage of continuous direct diaphragmatic visualization without the use of fluoroscopy, hence significantly minimizing radiation to both the patient and the operator. In addition, this technique does not require extra personnel to monitor the diaphragm using manual palpation. Further prospective studies of our and other methods for prevention of phrenic nerve palsy are required.