Apixaban versus warfarin in evaluation of progression of atherosclerotic and calcified plaques (prospective randomized trial).

Warfarin has been showed to increase vascular calcification. Apixaban, a direct factor Xa inhibitor, has no interaction with vitamin K and its effect on coronary plaques is unknown. We randomized and compared warfarin and apixaban on progression of coronary atherosclerotic plaques measured by coronary computed tomographic angiography in 66 subjects with non-valvular atrial fibrillation over the period of one-year follow up. There was significant higher total, calcified and low attenuation plaque volume in the group randomized to warfarin as compared to apixaban (all P < .05). Greater volume of total (ß2 = 28.54; P = .03), low attenuation plaque (ß2 = 3.58; P = .02) and calcified (ß2 = 14.10; P = .005) plaque progression was observed in the VKA_group.

Clonidine Overdose as an Unusual Cause of Heart Failure.

Clonidine is used as an antihypertensive medication due to its effect on decreasing peripheral vascular resistance and therefore lowering blood pressure. Alpha antagonism in the medulla and the posterior hypothalamus causing a reduction in sympathetic activation allows for clonidine to be used as an effective off-label treatment for attention-deficit/hyperactivity disorder (ADHD). This is a case of a 28-year-old female with hypertension, ADHD, and depression who developed acute heart failure with significant troponemia after ingesting 30 pills of clonidine. We illustrate the possible rare diagnosis of systolic heart failure and coronary vasospasm secondary to clonidine overdose.

Acute Pericarditis Leading to a Diagnosis of SLE: A Case Series of 3 Patients.

In systemic lupus erythematosus (SLE), cardiac manifestations are known to be present in up to 50% of patients. However, it is rare for acute pericarditis to be the leading symptom at the time of diagnosis of SLE occurring in up to 1% of patients. We present a case series in which 3 patients with no prior history of SLE presented with acute pericarditis. This was found to be the leading manifestation of their disease, which ultimately led to the diagnosis of SLE. These patients were initially treated with nonsteroidal anti-inflammatory drugs and colchicines; however, steroids and disease-modifying anti-rheumatologic agents were ultimately added to their medical therapy.

An Unusual Case of Paraquat-Induced Rhabdomyolysis and Hepatic Injury Presenting With Takotsubo Cardiomyopathy.

Takotsubo cardiomyopathy (TCM) is a syndrome of reversible left ventricular systolic dysfunction that, at presentation, can be easily conflated with acute coronary syndrome. TCM has a clinical preponderance for older, postmenopausal females. We report on a patient's case who presented with complaints of upper and lower extremity weakness with evidence of rhabdomyolysis and hepatic injury. Her occupation as a field worker exposed her to a toxic chemical known as paraquat, which has been banned by multiple countries across the world; a chemical we presume culminated in both. The subsequent clinical cascade and resulting acute physiological illness and emotional distress primed her to develop TCM. However, she neither endorsed chest pain nor dyspnea. Her subtle clinical presentation could have led to a missed diagnosis as she was also not in a fluid overloaded state consistent with the depressed left ventricular function discovered on transthoracic echo. The diagnostic uncertainty until coronary angiography is obtained, and its association with severe and acute emotional and physical stress prompts to a greater reliance on patient history to identify occupational and toxic exposures that can contribute to its development.

A Giant Left Intraventricular Thrombus Associated With Apical Hypertrophic Cardiomyopathy Mimics Cancer.

Hypertrophic cardiomyopathy (HCM) is a common disease that can be acquired due to chronic hypertension or via autosomal dominant inheritance. Several patterns of HCM have been described, of which a rare variant is apical hypertrophic cardiomyopathy (AHCM). Atrial thrombus is a well-recognized complication of HCM especially in the setting of atrial fibrillation (AF). However, left ventricular thrombus (LVT) formation is not nearly as prevalent as atrial thrombus. Here is a case of a 57-year-old Hispanic female with AHCM who presented with significant unintentional weight loss and unexplained anemia and was subsequently found to have a large left intraventricular mass suspicious for a tumor vs. ventricular thrombus. The diagnosis was complicated due to the large size of the mass and presenting symptoms suspicious of malignancy.

Echocardiographic Findings in Heart Failure Patients With Methamphetamine Use: A Case-Control Study.

Background Methamphetamine use is associated with cardiovascular disease and significant morbidity and mortality. There is only one previous study performed on echocardiographic parameters in patients with methamphetamine cardiomyopathy. Methods We performed a retrospective review of medical records in a county hospital in Southern California with a high population of methamphetamine users. We reviewed medical records and echocardiogram findings in patients seen in our institution from November 2019 to November 2020 who had cardiomyopathy with and without methamphetamine use. We excluded patients who either left the hospital or expired before appropriate assessment. We divided our patient population into a case group (methamphetamine users) and a control group (non-methamphetamine users) to study and compare their echocardiographic parameters. Results Case group included a total of 254 patients and control group included 268 patients. Majority of the patient population were males - 178 (70%) and 180 (67%) in the case and control group respectively. Age was found to be statistically significant with the younger population in the case group (p = 0.0000). Our analysis revealed statistically significant difference in methamphetamine users compared to non-users in regards to left ventricle ejection fraction (33.65% ± 18.02 vs. 41.55% ± 15.61, p=0.0000), left ventricle mass index (122.49 grams/m2 ± 40.66 vs. 108.62 grams/m2 ± 32.82, p=0.0000), left ventricle end diastolic volume index (85.91 mL/m2 ± 37.40 vs. 72.44 mL/m2 ± 25.44; p=0.0000) and marginally significant right ventricle systolic pressure (42.29mmHg ± 17.53 vs. 39.59mmHg ± 15.61; p=0.0540) Conclusion Our results indicated that methamphetamine users had echocardiogram findings with decreased ejection fraction and increased left ventricular mass index, end-diastolic volume index, and right ventricular systolic pressure consistent with worse dilated cardiomyopathy comparison to non-users.

References Values for Left Atrial Volumes, Emptying Fractions, Strains, and Strain Rates and Their Determinants by Age, Gender, and Ethnicity: The Multiethnic Study of Atherosclerosis (MESA).

RATIONALE AND OBJECTIVES: Left Atrial (LA) adverse remodeling is an important predictor of morbidity and mortality in several cardiovascular (CV) diseases. Our goals were to quantify and provide reference ranges for LA structure and function using feature tracking cine cardiac magnetic resonance. MATERIALS AND METHODS: 2526 participants of the Multiethnic Study of Atherosclerosis study who had feature tracking cine cardiac magnetic resonance derived LA data and were free of atrial fibrillation/flutter and prior CV events at year five follow-up examination (2010-2012) were included in this study. LA phasic indexed volumes: maximum (LAVi max), minimum (LAVi min), and preatrial contraction (LAVi preA); LA empty fractions: total, passive, and active (LAtEF, LApEF, and LAaEF); LA longitudinal strain: maximum and preatrial contraction (S max and S preA); and LA longitudinal strain rate: systolic (SR max) and early/late diastolic (SR e and SR a) were measured. Age, gender, and race/ethnicity-specific reference ranges were identified. Also, reference values in a select subgroup of healthy participants free of traditional CV risk factors at the time of exam date were reported. RESULTS: The mean ± SD for LAVi max, LAVi min, LAVi preA, S max, SR e, and SR a were in the 45-65-year-old participants: (33.8 ± 10 mL/m2), (14.5 ± 6.4 mL/m2), (24.8 ± 8.2 mL/m2), (34.6 ± 13.8 %), (-1.4 ± 0.7 s-1), (-2.1 ± 1 s-1) and in the ≥ 65-year-old participants: (35 ± 11.5 mL/m2), (16.6 ± 8.3 mL/m2), (27.6 ± 9.9 mL/m2), (31.2 ± 14.3 %), (-1 ± 0.6 s-1), (-2.1 ± 1 s-1) respectively. Younger individuals had Powered by Editorial Manager and ProduXion Manager from Aries Systems Corporation smaller LA volumes and better LA function compared to their older counterparts. Similar findings were observed in Chinese-Americans as compared to Whites. CONCLUSION: This study provides reference values of LA structure and function parameters from a healthy multiethnic community-based population aged 53-94 years evaluated by FTMRI.

Quantifying changes in size of arrhythmic photoplethysmography waveforms during a Valsalva maneuver for assessing cardiac filling pressure.

OBJECTIVE: We previously showed that the change in amplitude of a finger photoplethysmography waveform during the Valsalva maneuver reflects cardiac filling pressure. However, the automated determination of peaks and valleys to calculate amplitude is limited in significant arrhythmias such as atrial fibrillation and premature ventricular complexes, which are common in heart failure. The purpose of this study was to assess the change in size of the waveform by calculating the change in root mean square (RMS) of the signal, thereby utilizing the entire cardiac cycle, and to compare it to change in size of peak-to-valley amplitude. APPROACH: We compared the two approaches in signals obtained from participants of a prior study who were tested prior to a clinically indicated cardiac catheterization. Correlation between the two methods was assessed in cases without, and then with, significant arrhythmias including atrial fibrillation or premature ventricular complexes. MAIN RESULTS: Calculations from the two methods of peak-valley amplitude and RMS were highly correlated with each other in signals without (0.99, p < 0.0001, n = 252) and with significant arrhythmias (0.90, p < 0.0001, n = 34). SIGNIFICANCE: RMS analysis of photoplethysmography signal size during the Valsalva maneuver is highly correlated with the method of analyzing changes in peak-valley amplitude, but does not rely on identifying peaks and valleys. The RMS method may be a more robust automated method of assessing cardiac filling pressure in patients with significant arrhythmias.

Multivalvular Endocarditis Involving 3 Valves in a Nonsurgical Candidate.

Infective endocarditis is associated with high morbidity and mortality. Hence, early diagnosis and prompt intervention is crucial. Multivalvular endocarditis involving 3 or more valves is rarely reported with little information regarding best management or prognosis, particularly in nonsurgical patients. Conflicting guidelines regarding medical versus surgical treatment in multivalvular endocarditis exist with few studies describing the outcome of medically managed patients. We report the case of a previously healthy male presenting with infective endocarditis involving 3 valves further complicated by multiple septic emboli and deemed a nonsurgical candidate.

Isoproterenol Causing Coronary Vasospasm and ST Elevations During Tilt Table Testing.

Syncope is a sudden but reversible brief loss of consciousness secondary to an acute reduction of cerebral perfusion. Reflex syncope denotes neurologically mediated syncope, which includes vasovagal, carotid sinus syndrome, and other situational syncope. The most frequent form of syncope is vasovagal, which is triggered by emotional stress or prolonged standing, and may be diagnosed with the tilt table test. A thorough investigation of syncope is necessary as serious cardiovascular disorders may also be a cause. A tilt table test is a widely used tool utilized by clinicians to diagnose vasovagal syncope and is sometimes augmented with isoproterenol, a ß-sympathomimetic that acts on the heart. This report seeks to explain a case of a 48-year-old previously healthy woman who experienced inferior wall ST elevations during tilt table test supplemented with isoproterenol. There is reason to believe that the results of this patient's tilt table test were due to vasovagal syncope in conjunction with right coronary artery vasospasm.

Successful Clozapine Re-Challenge After Suspected Clozapine-Induced Myocarditis.

BACKGROUND Clozapine plays a unique role in the management of treatment-resistant schizophrenia (TRS). Clozapine re-challenge following an episode of myocarditis is controversial, with a very limited literature, although it may be crucial in the recovery of certain patients. To date and to the best of our knowledge, only 10 of 22 studied cases reported successful clozapine retrial after myocarditis. CASE REPORT We present the case of a 22-year-old Hispanic man with treatment-resistant schizophrenia and polysubstance use disorder (methamphetamine, cannabis, and alcohol) initiated on aggressive clozapine titration after lack of response to several other therapies. Approximately 16 days after clozapine trial, the patient developed cardiac function impairment, presenting with chest pain, notable elevation in several biomarkers (troponin: 0.72 ng/ml, ESR >100 mm/h, CRP: 20.8 mg/dl, and BNP: 999 ng/ml), and a depressed ejection fraction at 25%. Further assessments also showed positive hepatitis A serology. Following discontinuation of clozapine and providing supportive care, the patient's physical symptoms resolved. He had a relapse of psychotic symptoms, which were refractory to treatment with other antipsychotic agents. Subsequently, the patient underwent a second clozapine trial under close monitoring, with resolution of his psychosis. Repeated echocardiography demonstrated improved EF to 50%, transaminitis was resolved, repeat blood test results were normalized, and the patient was discharged while he was stabilized and asymptomatic. CONCLUSIONS This case adds to the previous case reports and suggests that clinicians may consider clozapine re-challenge following an episode of myocarditis based on clinical judgment, on a case-by-case basis, and under close monitoring. We highlight the need for development of clinical guidelines for clozapine re-challenge.

Transesophageal Versus Transthoracic Echocardiography for Assessment of Left Ventricular Diastolic Function.

Background: Transesophageal echocardiography (TEE) has not been compared to transthoracic echocardiography (TTE) for assessment of left ventricular diastolic function (LVDF). Left ventricular diastolic dysfunction is common in systemic lupus erythematosus (SLE), a disease model of premature myocardial disease. Methods: 66 patients with SLE (mean age 36±12 years, 91% women) and 26 age-and-sex matched healthy volunteers (mean age 34±11 years, 85% women) underwent TEE immediately followed by TTE. From basal four-chamber views, mitral inflow E and A velocities, E/A ratio, E deceleration time, isovolumic relaxation time, septal and lateral mitral E' and A' velocities, septal E'/A' ratio, mitral E to septal and lateral E' ratios, and pulmonary veins systolic to diastolic peak velocities ratio were measured. Measurements were averaged over 3 cardiac cycles and performed by 2 independent observers. Results: LVDF parameters were worse in patients than in controls by TEE and TTE (all p≤0.03). Most LVDF parameters were similar within each group by TEE and TTE (all p≥0.17). By both techniques, mitral E and A, mitral and septal E/A ratios, septal and lateral E', septal and lateral E/E' ratios, and average E/E' ratio were highly correlated (r=0.64-0.96, all p≤0.003); E deceleration time, isovolumic relaxation time, and septal A' velocities were moderately correlated (r=0.43-0.54, all p≤0.03); and pulmonary veins systolic to diastolic ratio showed the lowest correlation (r=0.27, p=0.04). Conclusion: By TEE and TTE, LVDF parameters were worse in SLE patients than in controls; and in both groups, LVDF parameters assessed by TEE and TTE were similar and significantly correlated.

Persistent Left Superior Vena Cava: Implications of Surgical Management.

Persistent left superior vena cava is the most common congenital anomaly of thoracic venous return, which results when the left anterior cardinal vein fails to regress. A 41-year-old African American male with a history of an unspecified childhood cardiac murmur presented to the emergency department with congestive heart failure exacerbation revealing an incidental finding of a persistent left superior vena cava. Ultimately, he required implantable cardioverter defibrillator placement and cardiac transplantation assessment. In the setting of advanced device placement or cardiac transplantation, a persistent left superior vena cava warrants several important clinical considerations at a center capable of addressing the possibility of a right-sided approach and transplantation irregularities.

Embolizing Massive Right Atrial Thrombus in a HIV-Infected Patient.

The risk of thromboembolism is increased when associated with the human immunodeficiency viral (HIV) infection. Various factors are involved in promoting thrombosis, and the presence of a patent foramen ovale augments the potential for a paradoxical embolism. We describe the case of a 56-year-old man receiving antiretroviral therapy with features of right heart failure and pulmonary embolism. Due to the high incidence of life-threatening thromboembolism in the HIV-infected group, the need for long-term anticoagulation has to be evaluated.

Rationale and design of a randomized trial of apixaban vs warfarin to evaluate atherosclerotic calcification and vulnerable plaque progression.

Vitamin K antagonists (VKAs) are known to increase vascular calcification, suggesting increased cardiovascular disease events. Apixaban is an oral direct factor Xa inhibitor superior to warfarin at preventing stroke or systemic embolism and may stabilize coronary atherosclerosis. The potential benefits of avoiding VKA therapy and the favorable effects of factor Xa inhibitors could contribute to cardiovascular disease event reduction. We hypothesized that apixaban inhibits vascular calcification and coronary atherosclerosis progression compared with warfarin in patients with atrial fibrillation (AF). This study is a single-center, prospective, randomized, open-label study. From May 2014 to December 2015, 66 patients with nonvalvular AF who experienced VKA therapy were enrolled. Patients were randomized into either warfarin or apixaban cohorts and followed for 52 weeks. The primary objective is to compare the rate of change in coronary artery calcification (CAC) from baseline to follow-up in apixaban vs warfarin cohorts. The key secondary objective is to compare the rate of incident plaques and quantitative changes in plaque types between patients randomized to either warfarin or apixaban cohorts using serial coronary computed tomography angiography. Expert readers will blindly assess CAC and coronary artery plaques. It is thought that this trial will result in significant differences in CAC and coronary artery plaque progression between the VKA and apixaban. The results are anticipated to provide a novel insight into treatment selection for AF patients. The study is registered at http://www.clinicaltrials.gov (NCT 02090075).

Usefulness of a Noninvasive Device to Identify Elevated Left Ventricular Filling Pressure Using Finger Photoplethysmography During a Valsalva Maneuver.

The high rate of re-hospitalization for heart failure might be reduced by improving noninvasive techniques for identifying elevated left ventricular (LV) filling pressure. We previously showed that changes in a finger photoplethysmography (PPG) waveform during the Valsalva maneuver (VM) reflect invasively measured LV end-diastolic pressure (LVEDP). We have since developed a hand-held device that analyzes PPG while guiding the expiratory effort of a VM. Here we assessed the sensitivity and specificity of this device for identifying elevated LVEDP in patients. We tested 82 participants (28 women), aged 40 to 85 years, before a clinically indicated left heart catheterization. Each performed a VM between 18 and 25 mm Hg for 10 seconds into a pressure transducer. PPG was recorded continuously before and during the VM. LVEDP was measured during the catheterization. An equation for calculating LVEDP was derived using (1) ratio of signal amplitudes: minimum during VM to average at baseline, (2) ratio of peak-to-peak time intervals: minimum during VM to average at baseline, and (3) mean blood pressure. Calculated and measured LVEDP were compared. The range of measured LVEDP was 4 to 35 mm Hg. Calculated LVEDP correlated with measured LVEDP (p <0.0001, r = 0.56). A calculated LVEDP >20 mm Hg had a 70% sensitivity and 86% specificity for identifying measured LVEDP >20 mm Hg (area under receiver-operating characteristic curve 0.83). In conclusion, a hand-held device for assessing LV filling pressure had high specificity and good sensitivity for identifying LVEDP >20 mm Hg, a clinically meaningful threshold in heart failure.

Mortality Among Patients Hospitalized With Heart Failure and Diabetes Mellitus: Results From the National Inpatient Sample 2000 to 2010.

BACKGROUND: Case fatality and hospitalization rates for US patients with heart failure (HF) have steadily decreased during the past several decades. Diabetes mellitus (DM), a risk factor for, and frequent coexisting condition with, HF continues to increase in the general population. METHODS AND RESULTS: We used the National Inpatient Sample to estimate overall as well as age-, sex-, and race/ethnicity-specific trends in HF hospitalizations, DM prevalence, and in-hospital mortality among 2.5 million discharge records from 2000 to 2010 with HF as primary discharge diagnosis. Multivariable logistic and Poisson regression were used to assess the impact of the above demographic characteristics on in-hospital mortality. Age-standardized hospitalizations decreased significantly in HF overall and in HF with DM. Age-standardized in-hospital mortality with HF declined from 2000 to 2010 (4.57% to 3.09%, Ptrend<0.0001), whereas DM prevalence in HF increased (38.9% to 41.9%, Ptrend<0.0001) as did comorbidity burden. Age-standardized in-hospital mortality in HF with DM also decreased significantly (3.53% to 2.27%, Ptrend<0.0001). After adjusting for year, age, and comorbid burden, males remained at 17% increased risk versus females, non-Hispanics remained at 12% increased risk versus Hispanics, and whites had a 30% higher mortality versus non-white minorities. Absolute mortality rates were lower in younger versus older patients, although the rate of decline was attenuated in younger patients. CONCLUSIONS: In-hospital mortality in HF patients with DM significantly decreased during the past decade, despite increases in DM prevalence and comorbid conditions. Mortality rate decreases among younger patients were significantly attenuated, and mortality disparities remain among important demographic subgroups.

Extensive biatrial thrombus straddling the patent foramen ovale and traversing into the left and right ventricle.

We report an extremely rare case of an extensive biatrial thrombus straddling a patent foramen ovale (PFO) extending into the bilateral ventricles in a patient presenting with an acute embolic stroke. Our patient further developed a massive saddle pulmonary embolus (PE) with haemodynamic instability during the course of his hospitalisation. The risks of pharmacological thrombolysis or surgical thrombectomy for PE in a haemodynamically unstable patient with recent embolic stroke posed a significant therapeutic dilemma. Ultimately, the decision was made to continue anticoagulation with unfractionated heparin followed by oral Coumadin. The patient responded well to therapy and at 1-month follow-up, a complete resolution of the thrombus was documented on transoesophageal echocardiogram with full clinical recovery of the patient.

Associations of electrocardiographic P-wave characteristics with left atrial function, and diffuse left ventricular fibrosis defined by cardiac magnetic resonance: The PRIMERI Study.

BACKGROUND: Abnormal P-terminal force in lead V1 (PTFV1) is associated with an increased risk of heart failure, stroke, atrial fibrillation, and death. OBJECTIVE: Our goal was to explore associations of left ventricular (LV) diffuse fibrosis with left atrial (LA) function and electrocardiographic (ECG) measures of LA electrical activity. METHODS: Patients without atrial fibrillation (n = 91; mean age 59.5 years; 61.5% men; 65.9% white) with structural heart disease (spatial QRS-T angle ≥105° and/or Selvester QRS score ≥5 on ECG) but LV ejection fraction >35% underwent clinical evaluation, cardiac magnetic resonance, and resting ECG. LA function indices were obtained by multimodality tissue tracking using 2- and 4-chamber long-axis images. T1 mapping and late gadolinium enhancement were used to assess diffuse LV fibrosis and presence of scar. P-prime in V1 amplitude (PPaV1) and duration (PPdV1), averaged P-wave-duration, PR interval, and P-wave axis were automatically measured using 12 SLTM algorithm. PTFV1 was calculated as a product of PPaV1 and PPdV1. RESULTS: In linear regression after adjustment for demographic characteristics, body mass index, maximum LA volume index, presence of scar, and LV mass index, each decile increase in LV interstitial fibrosis was associated with 0.76 mV*ms increase in negative abnormal PTFV1 (95% confidence interval [CI] -1.42 to -0.09; P = .025), 15.3 ms prolongation of PPdV1 (95% CI 6.9 to 23.8; P = .001) and 5.4 ms prolongation of averaged P-duration (95% CI 0.9-10.0; P = .020). LV fibrosis did not affect LA function. PPaV1 and PTFV1 were associated with an increase in LA volumes and decrease in LA emptying fraction and LA reservoir function. CONCLUSION: LV interstitial fibrosis is associated with abnormal PTFV1, prolonged PPdV1, and P-duration, but does not affect LA function.