Burden of cardiometabolic risk factors and vascular health.

BACKGROUND: Cardiometabolic risk factors diabetes, obesity, and hypertension are highly prevalent and contribute to increased cardiovascular disease (CVD). Endothelial dysfunction precedes CVD development. The current study aimed to investigate the EC transcriptome among individuals with varying degree of cardiometabolic risk. METHODS: Adult participants without CVD and various degrees of cardiometabolic risk factor burden (hypertension, diabetes, obesity) were included. Participants underwent brachial vein EC harvesting followed by RNA sequencing. To evaluate the association between cardiometabolic comorbidity burden and outcome transcripts we performed linear regression with multivariable models, adjusting for age, sex, and race/ethnicity. RESULTS: A total of 18 individuals were included in the present analysis (mean age 47 ± 14, 44% female, and 61% White adults). Endothelial cell RNA sequencing revealed 588 differentially expressed transcripts (p-adj <0.05) with excellent discrimination in unsupervised hierarchical clustering analysis. Gene ontology enrichment analysis revealed upregulated pathways associated with T-cell activation (NES = 2.22, p<0.001), leukocyte differentiation (NES= 2.16, p<0.001), leukocyte migration (NES= 2.12, p<0.001), regulation of cell-cell adhesion (NES= 1.91, p=0.006). Downregulated pathways of interest included endothelial cell proliferation (NES= -1.68, p=0.03) and response to interleukin-1 (NES= -1.61, p=0.04). Upregulated genes included VCAM1, CEACAM1, ADAM 17, and CD99L2, all with a log-2-fold change >3 and p-adj <0.05. These genes demonstrated a graded increase in mean normalized counts with increasing number of risk factors. CONCLUSIONS: We demonstrate a proinflammatory and pro-adhesive EC transcriptome associated with increased cardiometabolic risk factor burden offering insight into a potential mechanism linking these risk factors with the development of CVD.

The Impact of Cocaine Use and the Obesity Paradox in Patients With Heart Failure With Reduced Ejection Fraction Due to Non-ischemic Cardiomyopathy.

Background Obesity and illicit drugs are independent risk factors for developing heart failure (HF). However, recent studies have suggested that patients who already have HF and are obese have better clinical outcomes. We aim to study the effect of cocaine use on this obesity paradox phenomenon as it pertains to HF readmissions. Methodology In a retrospective chart analysis, we reviewed patients with a diagnosis of HF with reduced ejection fraction (HFrEF) admitted to Metropolitan Hospital in New York. We studied the association between body mass index (BMI) categories, namely, non-obese (<30 kg/m2) and obese (≥30 kg/m2), cocaine use, and the primary outcome (time to readmission for HF within 30 days after discharge). The interaction between cocaine and obesity status and its association with the primary outcome was also assessed. Results A total of 261 patients were identified. Non-obese status and cocaine use were associated with an increased hazard of readmission in 30 days (hazard ratio (HR) = 2.28, p = 0.049 and HR = 3.12, p = 0.004, respectively). Furthermore, cocaine users who were non-obese were over six times more likely to be re-admitted in 30 days compared to non-cocaine users who were obese (HR = 6.45, p = 0.0002). Conclusions Non-obese status and continued use of cocaine have a negative additive effect in impacting HF readmissions.

Refractory Heart Failure of Unknown Etiology May Be Cardiac Amyloid If Preceded by Hereditary Neurological Symptoms.

Transthyretin cardiac amyloidosis results from the deposition of transthyretin amyloid fibrils in the myocardium. This happens because of the misfolding of genetically normal (wild type - ATTR) or mutant (hereditary ATTR) transthyretin. The clinical presentation of hereditary ATTR cardiac amyloidosis is dependent on the exact site of the amino acid substitution. The V122I gene mutation is most common among people of African descent and usually manifests with cardiomyopathy. The mutations are transmitted in an autosomal dominant manner with variable penetrance and associated with clinical features occurring most commonly after the age of 40. The symptoms of heart failure (HF) may be preceded by several years of vague neurological symptoms which is more concerning if there is no clear explanation. A high index of suspicion is therefore crucial in ensuring prompt diagnosis and therapy, as this may favorably alter the gloomy prognosis associated with cardiac amyloidosis.

Rare Association of Takotsubo Cardiomyopathy with Right Bundle Branch Block in the Dual Setting of Asthma Exacerbation and Psychiatric Illness.

BACKGROUND Takotsubo cardiomyopathy is characterized by a transient left ventricular dysfunction without obstructive coronary artery disease that mimics an acute myocardial infarction. The electrocardiogram findings of Takotsubo cardiomyopathy usually present with ST-segment elevation or depression, T-wave inversion, left bundle branch block or high-grade atrioventricular block. CASE REPORT This is a report of a case of a 58-year-old male diagnosed with Takotsubo cardiomyopathy that occurred in the setting of an acute asthma exacerbation and psychiatric exacerbation with novel electrocardiogram findings of right bundle branch block. Transthoracic echocardiogram showed a preserved ejection fraction with left ventricular apical ballooning and hyperkinesis of the basal segments. The nuclear stress test showed a fixed perfusion defect at the apical segment, but the patient refused further testing such as coronary angiography. The patient was managed medically, and a repeat echocardiogram done after 8 weeks from discharge showed a complete resolution of the apical ballooning. CONCLUSIONS It is important to recognize that patients with psychiatric illness and asthma exacerbation are predisposed to develop Takotsubo cardiomyopathy. It is also reasonable to suspect Takotsubo cardiomyopathy in the presence of new electrocardiogram findings aside from those typically seen in acute myocardial infarction, especially if it is associated with apical ballooning.

Venous Thromboembolism Has a Variable Time of Occurrence in the Course of COVID-19: A Case Series.

The novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) which results in coronavirus disease 2019 (COVID-19) has had a devastating impact globally. Not much is fully understood about this disease. Acute respiratory distress syndrome (ARDS) appears to be the commonest complication among patients with COVID-19. However, venous thromboembolism (VTE) appears to be a common complication among patients with COVID-19 even with adequate anticoagulation during hospitalization. VTE may confer a poor outcome on its own or may exacerbate other common complications such as ARDS or cardiac injury. There are several diagnostic dilemmas with regards confirming VTE among patients with COVID-19 as there is a move to reduce the transfer of patients for angiographic studies or even venous Doppler ultrasonography because of the high transmissibility SARS-CoV-2. There is also the risk of worsening ARDS following fluid administration to prevent contrast nephropathy after angiographic studies.  It is, therefore, crucial to understand the timing of VTE occurrence in the setting of COVID-19, identify strategies for early diagnosis of VTE, therapeutic options as well as prognostic implications of VTE in the setting of COVID-19.

Prognostic Utility of Troponin I and N Terminal-ProBNP among Patients with Heart Failure due to Non-Ischemic Cardiomyopathy and Important Correlations.

BACKGROUND: Heart Failure (HF) is accompanied by a high cost of care and gloomy prognosis despite recent advances in its management. Therefore, efforts to minimize HF rehospitalizations is a major focus of several studies. METHODS: We conducted a retrospective cohort study of 140 patients 18 years and above who had baseline clinical parameters, echocardiography, NT-ProBNP, troponin I and other laboratory parameters following a 3-year electronic medical record review. Patients with coronary artery disease, preserved ejection fraction, pulmonary embolism, cancer, and end-stage renal disease were excluded. RESULTS: Of the 140 patients admitted with HF with reduced Ejection Fraction (HFrEF) secondary to non-ischemic cardiomyopathy, 15 were re-hospitalized within 30 days of discharge while 42 were rehospitalized within 6 months after discharge for decompensated HF. Receiver operating characteristic (ROC) cutoff points were obtained for NT-ProBNP at 5178 pg/ml and serum troponin I at 0.045 ng/ml. After Cox regression analysis, patients with HFrEF who had higher hemoglobin levels had reduced odds of re-hospitalization (p = 0.007) within 30 days after discharge. NT-ProBNP and troponin I were independent predictors of re-hospitalization at 6 months after discharge (p = 0.047 and p = 0.02), respectively, after Cox regression analysis. CONCLUSION: Troponin I and NT-ProBNP at admission are the best predictors of re-hospitalization 6 months after discharge among patients with HFrEF. Hemoglobin is the only predictor of 30 -day rehospitalization among HFrEF patients in this study. High-risk patients may require aggressive therapy to improve outcomes.

The relevance of serum albumin among elderly patients with acute decompensated heart failure.

OBJECTIVE: To assess the prognostic utility of serum albumin among elderly patients admitted for acute decompensated heart failure (ADHF) in terms of all-cause mortality and also to identify the predictors of hypoalbuminemia. METHODS: Retrospective cohort study of 119 elderly patients admitted for ADHF. Elderly patients were defined as patients over the age of 65 years. The patients were followed up for approximately 11 years. Patients with advanced renal failure, liver disease not due to HF, cancer and other causes of low life expectancy were excluded. Hypoalbuminemia was defined as serum albumin ≤ 2.9 g/dL. RESULTS: The study was made up of 65 females and 54 males with age ranging from 65 to 96 years. Of the 119 elderly patients with ADHF, there were 26 deaths. A significantly higher proportion of patients in the mortality group had an admission serum albumin level of ≤ 2.9 g/dL than those surviving (P = 0.011). After Cox's logistic regression, low albumin (P = 0.016), elevated direct bilirubin (P = 0.03), age greater than 85 (P = 0.008), lack of use of beta blockers (P = 0.0001) and left ventricular ejection fraction less than 35% (P = 0.005) increased the risk of death. Elevated serum creatinine (P = 0.0357) was the only predictor of hypoalbuminemia following multiple linear regression. CONCLUSIONS: Hypoalbuminemia may be an unrecognized marker of death in elderly patients with ADHF.

Relationship between pulmonary hypertension and outcomes among patients with heart failure with reduced ejection fraction.

Objectives: To identify predictors of pulmonary hypertension (PHT) and the predictive value of PHT for rehospitalization among patients with heart failure with reduced ejection fraction (HFrEF). Methods: A retrospective study of 351 hospitalized patients with heart failure (HF). Patients 18 years and above with HFrEF secondary to non-ischemic cardiomyopathy were reviewed. Patients with coronary artery disease, preserved ejection fraction and other secondary causes of PHT apart from HF were excluded. PHT as a predictor of 30-day and six-month re-admission was assessed as well as important possible predictors of PHT. Cox regression analysis, multiple linear regression as well as other statistical tools were employed as deemed appropriate. Results: Thirty-seven (37) and 99 patients were re-hospitalized within 30 days and 6 months after discharge for decompensated HF, respectively. After Cox regression analysis, higher hemoglobin reduced the odds of rehospitalization for decompensated HF (p = 0.015) within 30 days after discharge while higher pulmonary artery systolic pressure (PASP) (p = 0.002) and blood urea nitrogen (BUN) (p = 0.041) increased the odds of rehospitalization within 6 months of discharge. The predictors of the PHT among patients with HFrEF after multiple linear regression were low BMI (p = 0.027), increasing age (p = 0.006) and increased left atrial diameter (LAD) on echocardiography (p = 0.0001). Conclusion: Patients with HFrEF have a high predisposition to developing PHT if at admission, they have low BMI, dilated left atrium or are older. Patients with one or more of these attributes may need more intensive therapy to reduce the risk of developing PHT and in turn reduce readmission rates.

Low Skeletal Muscle Mass Independently Predicts Mortality in Patients with Chronic Heart Failure after an Acute Hospitalization.

BACKGROUND: Heart failure (HF) is a syndrome associated with exercise intolerance, and its symptoms are more common in patients with low skeletal muscle mass (SMM). Estimation of muscle mass can be cumbersome and unreliable, particularly in patients with varying body weight. The psoas muscle area (PMA) can be used as a surrogate of sarcopenia and has been associated with poor outcomes in other populations. OBJECTIVES: The aim of this study was to assess if sarcopenia is associated with the survival of patients with HF after an acute hospitalization. METHOD: We retrospectively studied a cohort of 160 patients with HF who had abdominopelvic computed tomography during an acute hospitalization. We obtained standardized measurements of their PMA and defined sarcopenia as the lowest gender-based tertile of the said area. The patients were followed until death or discontinuation of care. We used Kaplan-Meier estimates and Cox regression analysis to assess the relationship between sarcopenia and all-cause mortality. RESULTS: We found that the 52 patients with sarcopenia had 4.5 times the risk of all-cause mortality at 1 year compared to the rest of the cohort (CI 1.784-11.765; p = 0.0016) after adjusting for significant covariates. Stratification by age and sex revealed that this association could be limited to males and patients < 75 years old. CONCLUSION: The PMA, used as a surrogate of low SMM, is independently associated with an increased risk of late mortality after an acute hospitalization in patients with HF.

Clinical outcomes of Β-blocker therapy in cocaine-associated heart failure.

BACKGROUND: Cocaine is associated with deleterious effects in the heart, including HFrEF. Although ß-blockers are recommended for this condition in other populations, their use is discouraged in cocaine users due to the possibility of exacerbating cocaine-related cardiovascular complications. This study was designed to determine if patients with heart failure and a reduced ejection fraction (HFrEF) who continue to use cocaine have better outcomes when they receive ß-blocker therapy than when they do not. METHODS: We performed a retrospective analysis of 72 ß-blocker-naïve patients with HFrEF and active cocaine use. Patients who were prescribed ß-blockers as part of their therapy were compared to those who were not, and clinical and structural outcomes were compared after 12 months of treatment. RESULTS: When patients with HFrEF and active cocaine use received ß-blocker therapy, they were more likely to have an improvement in their New York Heart Association functional class (p = 0.0106) and left ventricular ejection fraction (p = 0.0031) than when they did not receive ß-antagonists. In addition, the risk of cocaine-related cardiovascular events (p = 0.0086) and of heart failure hospitalizations (p = 0.0383) was significantly lower in patients who received ß-blockade than those who did not. CONCLUSIONS: ß-Blocker therapy is associated with improvement in the exercise tolerance and the left ventricular ejection fraction in patients with HFrEF and active cocaine use. They are also associated with a lower incidence of cocaine-related cardiovascular events and HFrEF-related readmissions.

Brugada Phenocopy Induced by Recreational Drug Use.

Recreational drugs are commonly abused in all age groups. Intoxication with these substances can induce silent but significant electrocardiographic signs which may lead to sudden death. In this case study, we present a 49-year-old male with no medical comorbidities who came to the emergency department requesting opioid detoxification. Toxicology screen was positive for cocaine, heroin, and cannabis. Initial electrocardiogram (EKG) showed features of a Brugada pattern in the right precordial leads, which resolved within one day into admission. This presentation is consistent with the recently recognized clinical entity known as Brugada phenocopy.

Improvement in clinical outcomes of patients with heart failure and active cocaine use after ß-blocker therapy.

BACKGROUND: Cocaine use has a high prevalence in the United States and can be associated with significant cardiovascular disease, even in asymptomatic users. ß-Adrenergic receptor hyperactivation is the underlying pathophysiologic pathway of cocaine cardiotoxicity. ß-Blocker therapy is controversial in patients with active cocaine use. HYPOTHESIS: ß-Blocker therapy is associated with clinical improvement in patients with heart failure despite active cocaine use. METHODS: In a single-center, retrospective chart analysis, patients with newly diagnosed heart failure and active cocaine use who had been started on ß-blocker therapy were reviewed. The New York Heart Association (NYHA) functional class and the left ventricular ejection fraction (LVEF) were recorded at baseline and after 12 monthsnthsnths of ß-blocker use. Patients were excluded if they had been on prior ß-blocker therapy, had other reasons for volume overload, had chronic kidney disease stages G4 or G5, or had a life expectancy <12 months. RESULTS: Thirty-eight patients were identified; most were African American males. A statistically significant improvement was found in both NYHA functional class (P < 0.0001) and LVEF (P < 0.0001) after 12 months of ß-blocker therapy. No major adverse cardiovascular events occurred in this population. CONCLUSIONS: ß-Blocker use in cocaine users with heart failure with a reduced ejection fraction is associated with a lower NYHA functional class and a higher LVEF at 12-month follow-up. No major adverse cardiovascular events were observed.

Atrial Fibrillation in Patients with Heart Failure: Current State and Future Directions.

Heart failure affects nearly 26 million people worldwide. Patients with heart failure are frequently affected with atrial fibrillation, and the interrelation between these pathologies is complex. Atrial fibrillation shares the same risk factors as heart failure. Moreover, it is associated with a higher-risk baseline clinical status and higher mortality rates in patients with heart failure. The mechanisms by which atrial fibrillation occurs in a failing heart are incompletely understood, but animal studies suggest they differ from those that occur in a healthy heart. Data suggest that heart failure-induced atrial fibrosis and atrial ionic remodeling are the underlying abnormalities that facilitate atrial fibrillation. Therapeutic considerations for atrial fibrillation in patients with heart failure include risk factor modification and guideline-directed medical therapy, anticoagulation, rate control, and rhythm control. As recommended for atrial fibrillation in the non-failing heart, anticoagulation in patients with heart failure should be guided by a careful estimation of the risk of embolic events versus the risk of hemorrhagic episodes. The decision whether to target a rate-control or rhythm-control strategy is an evolving aspect of management. Currently, both approaches are good medical practice, but recent data suggest that rhythm control, particularly when achieved through catheter ablation, is associated with improved outcomes. A promising field of research is the application of neurohormonal modulation to prevent the creation of the "structural substrate" for atrial fibrillation in the failing heart.

Left Ventricular Aneurysm May Not Manifest as Persistent ST Elevation on Electrocardiogram.

BACKGROUND Electrocardiographic presentations of left ventricle aneurysms are diverse; however, a persistent ST segment elevation post myocardial infarction is most commonly reported. CASE REPORT The authors present a case of a 67-year-old man who presented to the emergency department after three days of chest pain and was found to have an acute myocardial infarction with an incidental finding of a left ventricular aneurysm. His surface electrocardiogram, however, demonstrated only inverted T waves in the precordial leads. He had a very elevated serum troponin I consistent with an acute myocardial injury which prompted a cardiac catheterization with angioplasty. Post angioplasty, he had persistent T wave inversions in the precordial leads. CONCLUSIONS It is important for clinicians to appreciate that the presence of newly inverted T waves in patients with a late presentation post myocardial infarction should raise a concern for a possible left ventricular aneurysm.