Greater Risk Of Cardiac Death Research Articles

Autonomic dysfunction in COVID-19 patients receiving mechanical ventilation: A cross-sectional study

Coronavirus disease 2019 (COVID-19) can damage cardiac tissue by increasing troponin levels and inducing arrhythmias, myocarditis, and acute coronary syndrome. To analyze the impact of COVID-19 on cardiac autonomic control in mechanically ventilated intensive care unit (ICU) patients. This cross-sectional analytical study of ICU patients of both sexes receiving mechanical ventilation was conducted in a tertiary hospital. Patients were divided into COVID-19-positive (COVID(+)) and COVID-19-negative (COVID(-)) groups. Clinical data were collected and heart rate variability (HRV) records obtained using a heart rate monitor. The study sample comprised 82 subjects: 36 (44%) in the COVID(-) group (58.3% female; median age, 64.5 years) and 46 (56%) in the COVID(+) group (39.1% females; median age, 57.5 years). The HRV indices were lower than the reference values. An intergroup comparison identified no statistically significant differences in the mean normal-to-normal (NN) interval, standard deviation of the NN interval, or root mean square of successive differences in NN intervals. The COVID(+) group had an increased low frequency (P = 0.05), reduced high frequency (P = 0.045), and increased low frequency/high frequency (LF/HF) ratio (P = 0.048). There was a weak positive correlation between LF/HF and length of stay in the COVID(+) group. Patients who received mechanical ventilation had lower overall HRV indices. COVID(+) patients who received mechanical ventilation had lower vagal HRV components. These findings likely indicate clinical applicability, as autonomic control impairments are associated with a greater risk of cardiac death.

Sex differences in coronary artery bypass grafting-related morbidity and mortality.

Coronary artery bypass grafting (CABG) is associated with both cardiovascular disease (CVD) and non-CVD traits. In addition, women's prognosis after coronary events and revascularizations is worse than in men. As the course of CVD in women differs from that of men, we performed a phenome-wide analysis on the sex differences in CABG -related morbidity and mortality. We performed an untargeted analysis on the sex differences in predictors and outcomes of CABG. We studied a sample of 176,680 FinnGen participants, including 5,950 individuals who underwent CABG (4,988 men and 962 women) and were followed between 1998 and 2019. Over 1,100 different traits were analyzed for both sexes and the results were adjusted with age, smoking status and BMI. Cox proportional hazards models with sex-trait interactions were used to estimate the associations between (1) traits and incident CABG; and (2) CABG and incident traits. In women, CABG was more strongly related to greater increases in risk of diseases such as hypertension, Alzheimer's, aortic aneurysms, gout, and chronic kidney disease compared to risk increases observed in men (all interaction p-values < 0.03). After CABG, men had 2.5-fold (p = 3.1E-15) and women 6.3-fold (p = 9.4E-08) greater risk of cardiac death compared to same-sex individuals who did not undergo CABG (p for interaction 8.2E-4). Moreover, the risk of death in women remained higher even 12 years after CABG, whereas the long-term risk of death in men was not increased, compared to same-sex individuals who did not undergo CABG. The adverse outcomes after CABG, both quantity and quality, also appear to differ between men and women. In women, CABG is related to greater long-term increases in risk of cardiac death and several other disease states than in men. Consideration should therefore be given to whether women receive adequate long-term post-operative therapy and follow-up as CABG is not associated with equally improved cardiovascular disease prognosis in women than in men.

Upright Cheyne-Stokes Respiration in Patients With Heart Failure

BackgroundCheyne-Stokes respiration (CSR) is believed to only occur in supine and sleeping conditions, and thus, CSR treatment is applied to those specific states. Although CSR has also been described in patients with heart failure (HF) during wakefulness, its persistence in an upright position is still unknown. ObjectivesThe purpose of this study was to assess the predictors, clinical correlates, and prognostic value of diurnal CSR in upright position. MethodsOutpatients with systolic HF underwent a comprehensive evaluation, including short-term respiratory monitoring with a head-up tilt test to investigate the presence of upright CSR, assessment of chemoreflex response to hypoxia and hypercapnia, and 24-h cardiorespiratory recording. At follow-up, cardiac death was considered as the endpoint. ResultsOf 574 consecutive patients (left ventricular ejection fraction 32 ± 9%; age 65 ± 13 years; 80% men), 195 (34%) presented supine CSR only, 82 (14%) presented supine and upright CSR, and 297 patients (52%) had normal breathing. Patients with upright CSR had the greatest apnea-hypopnea and central apnea index (at daytime and nighttime), the worst hemodynamic profile and exercise performance, increased plasma norepinephrine and N-terminal pro–B-type natriuretic peptide, and chemosensitivity to hypercapnia, which was the only independent predictor of upright CSR (odds ratio: 3.96; 95% confidence interval [CI]: 1.45 to 10.76; p = 0.007 vs. normal breathing; odds ratio: 4.01; 95% CI: 1.54 to 10.46; p = 0.004 vs. supine CSR). At 8-year follow-up, patients with upright CSR had the worst outcome (log-rank = 14.05; p = 0.001) and the presence of upright CSR independently predicted 8-year cardiac death (hazard ratio: 2.39; 95% CI: 1.08 to 5.29; p = 0.032). ConclusionsUpright CSR in HF patients is predicted by increased chemosensitivity to hypercapnia and is associated with worse clinical conditions and with a greater risk of cardiac death.

Long-term Patient Prognostication by Coronary Flow Reserve and Index of Microcirculatory Resistance: International Registry of Comprehensive Physiologic Assessment.

Background and ObjectivesRecent guideline recommends evaluation using of coronary flow reserve (CFR) and index of microcirculatory resistance (IMR) in patients with functionally insignificant stenosis. We evaluated clinical implications of CFR and IMR in patients with high fractional flow reserve (FFR) and deferred revascularization.MethodsA total of 867 patients (1,152 vessels) consigned to deferred revascularization who underwent comprehensive physiologic assessments were enrolled. Patients with high FFR (>0.80) were categorized by CFR (≤2) and IMR (≥23 U). Clinical outcome was assessed by patient-oriented composite outcome (POCO), a composite of any death, myocardial infarction (MI), and revascularization at 5 years.ResultsPatients with low CFR (≤2) showed significantly greater risk of POCO than those with high CFR (>2) in both high-FFR (p=0.024) and low-FFR (p=0.034) groups. In patients with high FFR, those with low CFR and high IMR (overt microvascular disease) displayed the greatest risk of POCO overall (p=0.015), surpassing those with high CFR and low IMR (HR, 2.873; 95% CI, 1.476–5.594; p=0.002) and showing significantly greater risk of cardiac death or MI (HR, 5.662; 95% CI, 1.984–16.154; p=0.001). Overt microvascular disease was independently associated with POCO in the high-FFR population (HR, 2.282; 95% CI, 1.176–4.429; p=0.015).ConclusionAmong patients with deferred revascularization, those with low CFR showed significantly greater risk of POCO than those with high CFR, regardless of FFR. In patients with high FFR, those with overt microvascular disease showed significantly greater risk of POCO and cardiac death or MI at 5-year, compared with the others.Trial RegistrationClinicalTrials.gov Identifier: NCT03690713

Stress Myocardial Perfusion PET Provides Incremental Risk Prediction in Patients with and Patients without Diabetes

To evaluate the prognostic value of myocardial perfusion PET in patients with and patients without diabetes mellitus. The authors performed a retrospective analysis of prospectively acquired data from a multicenter registry cohort of 7061 patients, including 1966 with diabetes mellitus, who underwent clinically indicated rest-stress rubidium 82 (82Rb) myocardial perfusion PET. The mean patient age (±standard deviation) was 63.3 years ± 13. Of the 7061 patients, 3348 were women (47.4%), 2296 (32.5%) had known coronary artery disease, and 1895 (26.8%) had previously undergone revascularization. The primary end point was cardiac death (n = 169) assessed at a mean of 2.5 years ± 1.5. The authors used Cox proportional hazards models and risk reclassification measures stratified according to diabetes status. In multivariable models adjusting for established clinical predictors, increasing magnitude of stress myocardial perfusion abnormality was associated with greater risk of cardiac death in patients with diabetes (hazard ratio [HR]: 7.2; 95% confidence interval [CI]: 3.1, 16.8) for severely abnormal myocardium compared with normal myocardium. The addition of stress myocardial perfusion imaging results significantly improved the fit of a clinical model for predicting cardiac death in patients with and patients without diabetes. Myocardial perfusion PET improved risk reclassification for cardiac death in patients with diabetes (category-based net reclassification index: 0.39; 95% CI: 0.15, 0.60, P < .001). Among diabetic patients, an abnormal myocardial perfusion PET scan was associated with increased risk of cardiac death (HR: 4.4; 95% CI: 2.0, 9.7) in all important clinical subgroups based on age, sex, obesity, or prior revascularization. In a large cohort of patients referred for clinical 82Rb stress PET, myocardial perfusion imaging results provided incremental risk prediction of cardiac death in patients with and patients without diabetes mellitus.© RSNA, 2019Supplemental material is available for this article.

Five-year outcomes of ST-elevation myocardial infarction versus non-ST-elevation acute coronary syndrome treated with biodegradable polymer-coated sirolimus-eluting stents: Insights from the CREATE trial

BackgroundLong-term outcome of drug-eluting stents (DES) for ST-elevation myocardial infarction (STEMI) versus non-ST-elevation acute coronary syndrome (NSTE-ACS) remains unclear. This study sought to compare the long-term outcomes of biodegradable polymer-coated DES in patients with STEMI versus NSTE-ACS. MethodsWe explored a post hoc analysis of the 5-year outcome of the CREATE trial in the subgroup of patients with STEMI (n=318) versus NSTE-ACS (n=1223) who were implanted with biodegradable polymer-coated DES. The primary outcome was the rate of major adverse cardiac events (MACE) at 5 years. Clopidogrel and aspirin for 6 months followed by chronic aspirin therapy were recommended. ResultsSTEMI patients showed a trend of increase in MACE (8.7% vs. 6.8%, log rank p=0.289) compared to NSTE-ACS patients at 5 years, and a greater risk of cardiac death (5.4% vs. 2.1%, log rank p=0.003), mainly driven by the higher cardiac death rate within the first month after stent placement (log rank p=0.003) and the last year of follow-up (log rank p=0.001). No significant difference in stent thrombosis was found between them (3.1% vs. 2.5%, log rank p=0.653). Prolonged clopidogrel therapy (>6 months) showed no effect on risk of MACE or stent thrombosis between the two groups (both p for interaction >0.1). ConclusionsSTEMI patients have a higher risk of cardiac mortality compared with NSTE-ACS patients after biodegradable polymer-coated DES placement, primarily attribute to more cardiac deaths that happened within the first month after the event and the last year of follow-up.

Abstract 20287: Cardiac MIBG Imaging Predicts Cardiac Death in Patients With Chronic Heart Failure , Irrespective of Hyperuricemia

Background: Elevated uric acid level is associated with an increased risk of adverse outcome in patients with chronic heart failure (CHF). On the other hand, cardiac metaiodobenzylguanidine (MIBG) imaging provides prognostic information in patients with CHF. However, there is no information available on the prognostic value of cardiac MIBG imaging in CHF patients, relating to hyperuricemia. Methods: We enrolled 113 CHF outpatients (NYHA2.0±0.6, ischemic origin 48%) with radionuclide LVEF &lt;40%(30±8%). The cardiac MIBG washout rate (WR) was calculated from the chest anterior view images obtained at 20 and 200 min after isotope injection. Abnormal WR was defined as &gt;27% as reported previously. At the entry, we measured serum uric acid level and hyperuricemia was define as &gt;7.0mg/dl. The primary end point was cardiac death. Reults: At the entry, 59 and 51 of 113 patients had abnormal WR and hyperuricemia, respectively. Serum uric acid level was significantly higher in patients with than without abnormal WR (7.3±1.8 vs 6.3±2.0 mg/dl, p=0.007). During the follow up period of 7.6±4.3 years, 35 patients had cardiac death. Cardiac death was significantly more often observed in patients with than without abnormal WR (47% vs 13%, p&lt;0.001) and hyperuricemia (42% vs 23%, p=0.034). At multivariate Cox analysis, abnormal WR and hyperuricemia were significantly independently associated with cardiac death (p=0.02 and p=0.03, respectively). Patients with abnormal WR had a significantly greater risk of cardiac death than those with normal WR in group with hyperuricemia (p=0.004, harard ratio: 6.5, 95%CI 1.8 to 23.4) and without hyperuricemia(p=0.001, hazard ratio: 4.4, 95%CI 1.5 to 13.2). Conclusion: Cardiac MIBG imaging provides the additional information to hyperuricemia in CHF.

Reclassification of Cardiovascular Risk in Patients With Normal Myocardial Perfusion Imaging Using Heart Rate Response to Vasodilator Stress

Previous studies have shown that patients with normal vasodilator myocardial perfusion imaging (MPI) findings remain at a greater risk of future cardiac events than patients with normal exercise MPI findings. The aim was to assess improvement in risk classification provided by the heart rate response (HRR) in patients with normal vasodilator MPI findings when added to traditional risk stratification. We retrospectively studied 2,000 patients with normal regadenoson or adenosine MPI findings. Risk stratification was performed using Adult Treatment Panel III framework. Patients were stratified by HRR (percentage of increase from baseline) into tertiles specific to each vasodilator. All-cause mortality and cardiac death/nonfatal myocardial infarction (MI) ≤2 years from the index MPI were recorded. During follow-up, 11.8% patients died and 2.7% patients experienced cardiac death/nonfatal MI in the adenosine and regadenoson groups, respectively. The patients who died had a greater Framingham risk score (12 ± 4 vs 11 ± 4, p= 0.009) and lower HRR (22± 16 vs 32 ± 21, p <0.0001). In an adjusted Cox model, the lowest tertile HRR was associated with an increased risk of mortality (hazard ratio 2.1) and cardiac death/nonfatal MI (hazard ratio 2.9; p <0.01). Patients in the highest HRR tertile, irrespective of the Adult Treatment Panel III category, were at low risk. When added to the Adult Treatment Panel III categories, the HRR resulted in net reclassification improvement in mortality of 18% and cardiac death/nonfatal MI of 22%. In conclusion, a blunted HRR to vasodilator stress was independently associated with an increased risk of cardiac events and overall mortality in patients with normal vasodilator MPI findings. The HRR correctly reclassified a substantial proportion of these patients in addition to the traditional risk classification models and identified patients with normal vasodilator MPI findings, who had a truly low risk of events.

Usefulness of Cardiac Iodine-123 Meta-Iodobenzylguanidine Imaging to Improve Prognostic Power of Seattle Heart Failure Model in Patients With Chronic Heart Failure

The Seattle Heart Failure Model (SHFM) is a validated prediction model that estimates the mortality in patients with chronic heart failure (CHF) using commonly obtained information, including clinical data, laboratory test results, medication use, and device implantation. In addition, cardiac iodine-123 meta-iodobenzylguanidine (MIBG) imaging provides prognostic information for patients with CHF. However, the long-term predictive value of combining the SHFM and cardiac MIBG imaging in patients with CHF has not been elucidated. To prospectively investigate whether cardiac iodine-123 MIBG imaging provides additional prognostic value to the SHFM in patients with CHF, we studied 106 outpatients with CHF who had radionuclide left ventricular ejection fraction < 40% (30 ± 8%). The SHFM score was obtained at enrollment, and the cardiac MIBG washout rate (WR) was calculated from anterior chest images obtained at 20 and 200 minutes after isotope injection. During a mean follow-up of 6.8 ± 3.5 years (range 0 to 13), 32 of 106 patients died from cardiac causes. A multivariate Cox analysis revealed that the WR (p = 0.0002) and SHFM score (p = 0.0091) were independent predictors of cardiac death. Kaplan-Meier analysis showed that patients with an abnormal WR (> 27%) had a significantly greater risk of cardiac death than did those with a normal WR for both those with a SHFM score of ≥ 1 (relative risk 3.3, 95% confidence interval 1.2 to 9.7, p = 0.01) and a SHFM score of ≤ 0 (relative risk 3.4, 95% confidence interval 1.2 to 9.6, p = 0.004). In conclusion, the cardiac MIBG WR provided additional prognostic information to the SHFM score for patients with CHF.

Differential prognostic significance of peri-infarction versus remote myocardial ischemia on stress technetium-99m sestamibi tomography in patients with healed myocardial infarction

Peri-infarction and remote myocardial ischemia involve different myocardial substrates, but their differential clinical implications have not been previously studied. We assessed the differential prognostic significance of peri-infarction and remote ischemia during long-term follow-up in patients with healed myocardial infarction. We studied 345 patients (59 ± 12 years old; 282 men) with previous myocardial infarction who demonstrated reversible perfusion abnormalities on exercise or dobutamine stress technetium-99m sestamibi tomography. Follow-up events for 5.5 ± 2.6 years were 60 deaths (17%; 40 cardiac deaths) and 25 reinfarctions (7%). Reversible perfusion abnormalities were detected in the remote region in 129 patients (37%), the peri-infarction region in 142 patients (41%), and in both regions in 74 patients (21%). The annual rates of cardiac death in these groups were 1.2%, 2.8%, and 2.9%, respectively (p <0.01). The annual rates of reinfarction were 1%, 1.5%, and 0.9%, respectively (p = NS). In a multivariate analysis model, independent predictors of cardiac death were history of heart failure (risk ratio [RR] 2.8, 95% confidence interval [95% CI] 1.2 to 7), diabetes mellitus (RR 4.1, 95% CI 1.9 to 8.9), summed score at rest (RR 1.4, 95% CI 1.1 to 3.1), and peri-infarction ischemia (RR 2.6, 95% CI 1.1 to 6.1). Predictors of reinfarction were age (RR 1.03, 95% CI 1.01 to 1.07) and diabetes mellitus (RR 3.3, 95% CI 1.2 to 9.1). Peri-infarction ischemia assessed by stress technetium-99m sestamibi tomography is associated with a greater risk of cardiac death than is remote ischemia. The risk of reinfarction is not related to the location of ischemia.

Adenosine myocardial perfusion single-photon emission computed tomography in women compared with men: Impact of diabetes mellitus on incremental prognostic value and effect on patient management

ObjectivesThis study was designed to assess the incremental prognostic value of adenosine stress myocardial perfusion single-photon emission computed tomography (MPS) in women versus men, and to explore the prognostic impact of diabetes mellitus. BackgroundLimited data are available regarding the incremental value of adenosine stress MPS for the prediction of cardiac death in women versus men and the impact of diabetes mellitus on post-adenosine MPS outcomes. MethodsOf 6,173 consecutive patients who underwent rest thallium-201/adenosine technetium-99m sestamibi MPS, 254 (4.1%) were lost to follow-up, and 586 with early revascularization ≤60 days after MPS were censored, leaving 2,656 women and 2,677 men. ResultsWomen had significantly smaller adenosine stress, rest, and reversible defects than men. During 27.0 ± 8.8 month follow-up, cardiac death rates were lower in women than men (2.0%/year vs. 2.7%/year, respectively, p < 0.05). Before and after risk adjustment, cardiac death risk increased significantly in both men and women as a function of MPS results. Multivariable models revealed that MPS results provided incremental prognostic value over pre-scan data for the prediction of cardiac death in both genders. Also, while comparative unadjusted rates of early (≤60 days post-test) coronary angiography (17% vs. 23%) and revascularization (8% vs. 12%) were significantly lower in women (p < 0.05), after adjusting for MPS, these rates were similar in men and women. Importantly, diabetic women had a significantly greater risk of cardiac death compared with other patients. Also, after risk adjustment, patients with insulin-dependent diabetes mellitus (IDDM) had higher risk of cardiac death for any MPS result than patients with non–insulin-dependent diabetes mellitus. ConclusionsThe findings suggest that adenosine MPS has comparable incremental value for prediction of cardiac death in women and men and that MPS is appropriately influencing subsequent invasive management decisions in both genders. Diabetic women and patients with IDDM appear to have greater risk of cardiac death than other patients for any MPS result.

Functional and prognostic significance of exercise-induced ventricular arrhythmias in patients with suspected coronary artery disease

Our aims were to assess (1) the relation between exercise-induced ventricular arrhythmia (VA) and myocardial wall motion abnormalities during exercise echocardiography in patients with suspected coronary artery disease (CAD), and (2) the effect of this relation on outcome. We studied the clinical and prognostic significance of exercise-induced VA in 1,460 patients (mean age 64 ± 10 years; 867 men) with intermediate pretest probability of CAD and no history of previous myocardial infarction or revascularization who underwent exercise echocardiography. Exercise-induced VA occurred in 146 patients (10%). Compared with patients without VA, those with VA had a greater prevalence of abnormal exercise echocardiographic findings (48% vs 29%, p = 0.001) and ischemia on exercise echocardiography (39% vs 22%, p = 0.001), greater increase in wall motion score index with exercise (0.14 ± 0.28 vs 0.06 ± 0.18, p <0.0001), and a greater percentage of abnormal segments with exercise (21 ± 30% vs 9 ± 19%, p <0.0001). During follow-up (median 2.7 years), cardiac death and nonfatal myocardial infarction occurred in 36 patients. In multivariate analysis of combined clinical and exercise stress test variables, independent predictors of cardiac events were exercise-induced VA (chi-square 4.7, p = 0.03) and exercise heart rate (chi-square 18, p = 0.0001). The percentage of abnormal myocardial segments with exercise echocardiography was the most powerful predictor of VA (chi-square 31, p = 0.0001) and cardiac events (chi-square 15, p = 0.0001). In patients with suspected CAD, exercise-induced VA is associated with a greater risk of cardiac death and nonfatal myocardial infarction. This risk is attributed to the relation between VA and the extent and severity of left ventricular functional abnormalities with exercise.

Patients with depression are less likely to follow recommendations to reduce cardiac risk during recovery from a myocardial infarction.

Patients with depression are at greater risk of cardiac death in the first few months after a myocardial infarction (MI). This study was performed to determine whether depression affects adherence to recommendations intended to reduce the risk of cardiac events after an MI. All consenting patients admitted to a university-affiliated teaching hospital during an 18-month period were interviewed 3 to 5 days following an acute MI using the Beck Depression Inventory to assess symptoms of depression and using the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition, to determine the presence of major depression and/or dysthymia. Accessible survivors (n=204; 116 men and 88 women) were interviewed by telephone 4 months later using the Medical Outcomes Study Specific Adherence Scale to measure self-reported adherence to recommendations to modify cardiac risk. Patients who were found in the hospital to have symptoms of at least mild to moderate depression (Beck Depression Inventory score > or =10, n=35 [17.2%]) or to have major depression and/or dysthymia (n=31 [15.2%]) reported lower adherence to a low-fat diet, regular exercise, reducing stress, and increasing social support 4 months later. Those with major depression and/or dysthymia also reported taking medications as prescribed less often than those without major depression and/or dysthymia. Diabetic patients with major depression and/or dysthymia were less likely to follow a diet for patients with diabetes than diabetic patients without depression. Patients with depression following an acute MI are less likely to adhere to recommended behavior and lifestyle changes intended to reduce the risk of subsequent cardiac events. This finding could explain why depression in the hospital is related to long-term prognosis in patients recovering from an MI.