Using Augmented Mean Arterial Pressure to Identify High Mortality Risk Patients With Moderate Aortic Stenosis.

OBJECTIVE: To study the usefulness of a novel echocardiographic marker, augmented mean arterial pressure (AugMAP = [(mean aortic valve gradient + systolic blood pressure) + (2 × diastolic blood pressure)] / 3), in identifying high-risk patients with moderate aortic stenosis (AS). PATIENTS AND METHODS: Adults with moderate AS (aortic valve area, 1.0-1.5 cm2) at Mayo Clinic sites from January 1, 2010, through December 31, 2020, were identified. Baseline demographic, echocardiographic, and all-cause mortality data were retrieved. Patients were grouped into higher and lower AugMAP groups using a cutoff value of 80 mm Hg for analysis. Kaplan-Meier and Cox regression models were used to assess the performance of AugMAP. RESULTS: A total of 4563 patients with moderate AS were included (mean ± SD age, 73.7±12.5 years; 60.5% men). Median follow-up was 2.5 years; 36.0% of patients died. The mean ± SD left ventricular ejection fraction (LVEF) was 60.1%±11.4%, and the mean ± SD AugMAP was 99.1±13.1 mm Hg. Patients in the lower AugMAP group, with either preserved or reduced LVEF, had significantly worse survival performance (all P<.001). Multivariate Cox regression showed that AugMAP (hazard ratio, 0.962; 95% CI, 0.942 to 0.981 per 5-mm Hg increase; P<.001) and AugMAP less than 80 mm Hg (hazard ratio, 1.477; 95% CI, 1.241 to 1.756; P<.001) were independently associated with all-cause mortality. CONCLUSION: AugMAP is a simple and effective echocardiographic marker to identify high-risk patients with moderate AS independent of LVEF. It can potentially be used in the candidate selection process if moderate AS becomes indicated for aortic valve intervention in the future.

Transcatheter Aortic Valve Replacement Prognostication with Augmented Mean Arterial Pressure.

BACKGROUND: Post-transcatheter aortic valve replacement (TAVR) patient outcome is an important research topic. To accurately assess post-TAVR mortality, we examined a family of new echo parameters (augmented systolic blood pressure (AugSBP) and arterial mean pressure (AugMAP)) derived from blood pressure and aortic valve gradients. METHODS: Patients in the Mayo Clinic National Cardiovascular Diseases Registry-TAVR database who underwent TAVR between 1 January 2012 and 30 June 2017 were identified to retrieve baseline clinical, echocardiographic and mortality data. AugSBP, AugMAP and valvulo-arterial impedance (Zva) (Zva) were evaluated using Cox regression. Receiver operating characteristic curve analysis and the c-index were used to assess the model performance against the Society of Thoracic Surgeons (STS) risk score. RESULTS: The final cohort contained 974 patients with a mean age of 81.4 ± 8.3 years old, and 56.6% were male. The mean STS risk score was 8.2 ± 5.2. The median follow-up duration was 354 days, and the one-year all-cause mortality rate was 14.2%. Both univariate and multivariate Cox regression showed that AugSBP and AugMAP parameters were independent predictors for intermediate-term post-TAVR mortality (all p < 0.0001). AugMAP1 < 102.5 mmHg was associated with a 3-fold-increased risk of all-cause mortality 1-year post-TAVR (hazard ratio 3.0, 95%confidence interval 2.0-4.5, p < 0.0001). A univariate model of AugMAP1 surpassed the STS score model in predicting intermediate-term post-TAVR mortality (area under the curve: 0.700 vs. 0.587, p = 0.005; c-index: 0.681 vs. 0.585, p = 0.001). CONCLUSIONS: Augmented mean arterial pressure provides clinicians with a simple but effective approach to quickly identify patients at risk and potentially improve post-TAVR prognosis.

Surgical versus catheter ablation in atrial fibrillation: A systematic review and meta-analysis of randomized controlled trials.

INTRODUCTION: Atrial fibrillation (AF) is the most common cardiac arrhythmia with a high stroke and mortality rate. The video-assisted thoracoscopic radiofrequency pulmonary vein ablation is a treatment option for patients who fail catheter ablation. Randomized data comparing surgical versus catheter ablation are limited. We performed a meta-analysis of randomized control trials to explore the outcome efficacy between surgical and catheter radiofrequency pulmonary vein ablation in patients with AF. METHODS: We comprehensively searched the databases of MEDLINE and EMBASE from inception to December 2020. Included studies were published randomized control trials that compared video-assisted thoracoscopic and catheter radiofrequency pulmonary vein ablation. Data from each study were combined using the fixed-effects, generic inverse variance method of DerSimonian, and Laird to calculate odds ratios and 95% confidence intervals. RESULTS: Six studies from November 2013 to 2020 were included in this meta-analysis involving 511 AF patients (79% paroxysmal) with 263 catheter ablation (mean age 56 ± 3 years) and 248 surgical ablations (mean age 52 ± 4 years). Catheter ablation was associated with increased atrial arrhythmias recurrence when compared to surgical ablation (pooled relative risk = 1.85, 95% confidence interval: 1.44-2.39, p < .001, I2 = 0.0%) but associated with less total major adverse events (pooled relative risk = 0.29, 95% confidence interval: 0.16-0.53, p < .001, I2 = 0.0%). In subgroup analysis, catheter ablation was associated with increased AF recurrence in refractory paroxysmal AF when compared to surgical ablation (pooled relative risk = 2.47, 95% confidence interval: 1.31-4.65, p = .005, I2 = 0.0%) but not in persistent AF (relative risk = 1.09, 95% confidence interval: 0.60-2.0, p = .773). CONCLUSION: Catheter ablation was associated with higher atrial arrhythmia recurrence when compared with surgical ablation. However, our study suggests that the benefit of surgical ablation in patients with persistent AF is unclear. More studies and alternative ablation strategies investigation in persistent AF are warranted.

Does the Age of Sudden Cardiac Death in Family Members Matter in Brugada Syndrome?

Background Brugada syndrome is an inherited cardiac channelopathy associated with major arrhythmic events (MAEs). The presence of a positive family history of sudden cardiac death (SCD) as a risk predictor of MAE remains controversial. We aimed to examine the association between family history of SCD and MAEs stratified by age of SCD with a systematic review and meta-analysis. Methods and Results We searched the databases of MEDLINE and EMBASE from January 1992 to January 2020. Data from each study were combined using the random-effects model. Fitted metaregression was performed to evaluate the association between the age of SCD in families and the risk of MAE. Twenty-two studies from 2004 to 2019 were included in this meta-analysis involving 3386 patients with Brugada syndrome. The overall family history of SCD was not associated with increased risk of MAE in Brugada syndrome (pooled odds ratio [OR], 1.11; 95% CI, 0.82-1.51; P=0.489, I2=45.0%). However, a history of SCD in family members of age younger than 40 years of age did increase the risk of MAE by ≈2-fold (pooled OR, 2.03; 95% CI, 1.11-3.73; P=0.022, I2=0.0%). When stratified by the age of cut point at 50, 45, 40, and 35 years old, a history of SCD in younger family member was significantly associated with a higher risk of MAE (pooled OR, 0.49, 1.30, 1.51, and 2.97, respectively; P=0.046). Conclusions A history of SCD among family members of age younger than 40 years was associated with a higher risk of MAE.

Baseline thrombocytopenia in acute coronary syndrome: The lower, the worse.

BACKGROUND: Patients with baseline thrombocytopenia can have increased mortality and morbidity, but are typically excluded from randomized clinical trials studying acute coronary syndromes (ACS). We sought to better define the effect thrombocytopenia on clinical outcomes in ACS patients. METHODS: Patients identified from the NCDR Chest Pain registry at Mayo Clinic Arizona from Oct 2015 to Sep 2018 were retrospectively classified into two groups: TP (platelet <150 × 103 µL) and control (platelet ≥150 × 103 µL). The groups were analyzed for the clinical outcome (all-cause mortality, major adverse cardiac events (MACE), and bleeding events). The TP group was divided into moderate-severe thrombocytopenia (TPmod; platelet 50-100 × 103 µL) and mild thrombocytopenia (TPmild; platelet 100-150 × 103 µL) for further analysis. P-value <0.05 is considered significant. RESULTS: Five hundred and thirty-six patients were identified, and 72 patients (13%) had thrombocytopenia. The median follow-up time was 1.1 years. The TP group was older (TP vs. control: mean age 73 ± 13 years vs. 70 ± 13 years; P = 0.026). In patients discharged on dual-antiplatelet therapy, the TP group had higher all-cause mortality (23% vs. 7.3%; P = 0.007) but not major bleeding events (11% vs. 5.0%; P = 0.123). Only all-cause mortality increased with the severity of thrombocytopenia (TPmod vs. TPmild vs. control: 33% vs. 24% vs. 7.3%; P = 0.007). CONCLUSIONS: In patients with ACS, baseline thrombocytopenia is associated with increased all-cause mortality and all bleeding events without net MACE benefit. Further study is needed to identify the optimal antiplatelet strategy in this higher risk population.

Long-Term Clinical Outcomes of Underdosed Direct Oral Anticoagulants in Patients with Atrial Fibrillation and Atrial Flutter.

BACKGROUND: Although direct oral anticoagulants (DOACs) have been shown to be effective at reducing the risk of stroke in patients with atrial fibrillation/flutter (AF), they are sometimes underdosed off-label to mitigate their associated higher bleeding risk. We sought to evaluate frequency and clinical outcomes of inappropriate underdosing of DOACS in patients with AF. METHODS: We conducted a study of subjects with AF who had a clinical indication for stroke prophylaxis (with a congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke or transient ischemic attack, vascular disease, age 65 to 47 years, sex category [CHA2DS2-VASc] of 2 or greater) and were prescribed 1 of the 4 clinically approved DOACs (apixaban, rivaroxaban, dabigatran, or edoxaban). We compared all-cause mortality, composite of stroke and systemic embolism, composite of myocardial infarction (MI), acute coronary syndromes (ACS), and coronary revascularization, and major bleeding between patients appropriately dosed and inappropriately underdosed. RESULTS: A total of 8125 patients met inclusion criteria, with a mean follow up of 2.2 ± 2 years. Of those, 1724 patients (21.2%) were inappropriately dosed. After adjusting for baseline variables, there was no difference in all-cause mortality, risk of stroke or systemic embolism, International Society on Thrombosis and Haemostasis (ISTH) major bleeding, or composite of myocardial infarction, acute coronary syndromes, or coronary revascularization between patients appropriately dosed and inappropriately underdosed. In subgroup analysis, only apixaban demonstrated an increased incidence all-cause mortality (hazard ratio [HR] 1.24, 95% confidence interval [CI] 1.03-1.49) with inappropriate underdosing. There was no difference in the remaining clinical outcomes noted on subgroup analysis. CONCLUSION: Underdosing of DOACs did not minimize risk of bleeding, systemic embolization or all-cause mortality in patients with AF. Inappropriate underdosing with apixaban in particular was associated with increased all-cause mortality.

Relative contribution of modifiable risk factors for incident atrial fibrillation in Hispanics, African Americans and non-Hispanic Whites.

BACKGROUND: Contribution of modifiable risk factors for the risk of new onset atrial fibrillation (AF) in minority populations is poorly understood. Our objective was to compare the population attributable risk (PAR) of various risk factors for incident AF between Hispanic, African American and non-Hispanic Whites. METHODS: An ECG/EMR database was interrogated for individuals free of AF for development of subsequent AF from 2000 to 2013. Cox regression analysis controlled for age > 65, male gender, body mass index > 40 kg/m2, systolic blood pressure > 140 mm Hg, diabetes mellitus, heart failure, socioeconomic status less than the first percentile in New York State, and race/ethnicity. PAR was calculated as (prevalence of X) ∗ (HR - 1)/HR, where HR is the hazard ratio, and X is the risk factor. RESULTS: 47,722 persons free of AF (43% Hispanic, 37% Black and 20% White) were followed for subsequent incident AF. Hypertension in African Americans and Hispanics had a 7.93% and 7.66% greater PAR compared with non-Hispanics Whites. Similar findings existed for the presence of heart failure, with a higher PAR in non-Whites compared to Whites. CONCLUSION: In conclusion, modifiable risk factors play an important role in the risk of incident AF. Higher PAR estimates in African Americans and Hispanics were observed for elevated systolic blood pressure and heart failure. Identification of these modifiable risk factors for atrial fibrillation in non-White minorities may assist in targeting better prevention therapies and planning from a public health perspective. No funding sources were used for this study.

Clinical Context and Detection of the Murmur of Advanced Aortic Stenosis.

OBJECTIVES: Auscultation is an important clue to the presence of aortic stenosis (AS). We sought to assess the effect of symptom status, prior knowledge of diagnosis, and other patient factors on murmur detection. METHODS: Patients with moderate-to-severe AS by echocardiography at a single center between June 2015 and June 2016 were included. Five consecutive patient encounters (inpatient and outpatient) within 12 months before the echocardiogram were analyzed. RESULTS: Ninety-five patients (418 different clinician encounters) were studied. The murmur of AS was identified by only 39% of clinicians. In multivariate analysis, significant determinants of murmur detection were examination in outpatient setting (odds ratio [OR] 3.40, 95% confidence interval [CI] 1.75-6.61), known history of AS (OR 2.77, 95% CI 1.53-5.01), female sex (OR 1.97, 95% CI 1.07-3.60), and presence of symptoms (OR 1.91 95% CI 1.12-3.26). Compared with the murmur detection findings by clinicians in medicine, the findings of surgical specialty clinicians were significantly lower (OR 0.12, 95% CI 0.06-0.26, P < 0.001). CONCLUSIONS: In this real-world assessment, clinical context played an important role in the auscultation of AS murmur. The findings have important implications for the clinical diagnosis of asymptomatic advanced AS.

Highly Probable Drug Reaction With Eosinophilia and Systemic Symptoms Syndrome Associated With Lenalidomide.

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a life-threatening hypersensitivity reaction to medications. We report a case of a 75-year-old African American female who presented with generalized rash with desquamation and malodorous secretions. She was febrile and hypotensive, and required vasopressors for hemodynamic instability. Sepsis secondary to skin or soft tissue infection was considered initially. However, she recently was started on lenalidomide for treatment of her multiple myeloma, and her white blood cell count of 17 K/µL with 55% eosinophils along with peripheral smear showing eosinophilia suggested lenalidomide-induced rash. Lenalidomide was discontinued, and methylprednisolone was initiated. Four days after lenalidomide discontinuation, vasopressors were discontinued. Blood cultures did not exhibit any growth. The Niranjo Adverse Drug Reaction Probability Scale score of 9 suggests lenalidomide was a highly probable cause of DRESS syndrome. The temporal relation of lenalidomide administration and development of symptoms plus improvement of rash with the discontinuation of lenalidomide and reappearance on restarting lenalidomide in the follow-up clinic strengthens our suspicion of lenalidomide-induced DRESS syndrome. Cases of lenalidomide-induced DRESS syndrome are sparse; however, DRESS syndrome is fatal in approximately 10% of patients. Providers should be aware and keep a vigilant eye out for this adverse reaction with lenalidomide.

Circadian Periodicity of Ischemic Heart Disease: A Systematic Review of the Literature.

The authors performed a MEDLINE search to identify reports, published during the last 20 years, focused on circadian variation of acute myocardial infarction (AMI), and prevalence and the ratios between the number of events per hour during the morning and the other hours of the day were calculated. Despite the optimization of interventional and medical therapy of AMI since the first reports of circadian patterns in AMI occurrence, it was found that such a pattern still exists and that AMI happens most frequently in the morning hours.

Iatrogenic Right-Sided Pneumothorax Presenting as ST-Segment Elevation: A Rare Case Report and Review of Literature.

Pneumothorax is a well-recognized complication of central venous line insertion (CVL). Rarely, pneumothorax can lead to electrocardiogram (ECG) findings mimicking ST-segment elevation myocardial infarction. We present a 63-year-old man with iatrogenic right-sided pneumothorax who developed ST-segment elevation on a 12-lead ECG suggestive of myocardial infarction. The ECG findings completely resolved after needle decompression and chest tube placement. This case points up this rare electrocardiographic finding with discussion of possible mechanisms and differential diagnosis.

Association of Obesity With In-Hospital Mortality of Cardiogenic Shock Complicating Acute Myocardial Infarction.

Several previous studies have shown obesity to be counterintuitively associated with more favorable mortality in patients with acute myocardial infarction (AMI); however, the association of obesity with in-hospital mortality of cardiogenic shock complicating AMI has not been previously examined. We queried the 2004 to 2013 National Inpatient Sample databases to identify all patients ≥18 years hospitalized with the principal diagnosis of AMI. Multivariable regression models adjusting for demographics, hospital characteristics, and co-morbidities were used to examine differences in incidence and in-hospital mortality of cardiogenic shock complicating AMI between obese and nonobese patients. Of 6,097,817 patients with AMI, 290,894 (4.8%) had cardiogenic shock. There was no difference in risk-adjusted incidence of cardiogenic shock between obese and nonobese patients (adjusted odds ratio 1.00, 95% CI 0.98 to 1.01; p = 0.46). Of the patients with cardiogenic shock complicating AMI, 8.9% had a documented diagnosis of obesity. Obese patients were on average 6 years younger and had higher prevalence of most cardiovascular co-morbidities. Obese patients were more likely to receive revascularization (73.0% vs 63.4%, p <0.001) and had lower risk-adjusted in-hospital mortality compared with nonobese patients (28.2% vs 36.5%; adjusted odds ratio 0.89, 95% CI 0.86 to 0.92; p <0.001). Similar findings were seen in subgroups of patients with cardiogenic shock complicating ST elevation or non-ST elevation MI. In conclusion, this large retrospective analysis of a nationwide cohort of patients with cardiogenic shock complicating AMI demonstrated that obese patients were younger, more likely to receive revascularization, and had modestly lower risk-adjusted in-hospital mortality compared with nonobese patients.

Controversies in postoperative atrial fibrillation after noncardiothoracic surgery: clinical and research implications.

Post operative atrial fibrillation after non-cardiothoracic surgery is an increasingly common problem. There is little high quality data to guide clinicians in risk prediction as well as short term and long term management. There appears to be a significant risk of recurrent atrial fibrillation and stroke but effective screening strategies have not been tested. In this commentary, we delineate various controversies in the management of post operative atrial fibrillation and briefly review the available evidence. Prospective studies in this clinically important area of cardiology should be encouraged.