Fundamentals of Light Chain Cardiac Amyloidosis: A Focused Review.

The estimated prevalence of AL CA in the US is approximately 8-12 cases per million. Almost 30-50% diagnosed cases of AL amyloid in the US have multisystem involvement, including cardiac involvement. Even with the availability of advanced diagnostic testing and novel therapies, prognosis remains poor. It is overlooked as a cause of heart failure with preserved ejection fraction leading to a delay in diagnosis when management options are limited and associated with poor survival outcomes. Therefore, the education of physicians is needed to ensure that it would be highly considered as a differential diagnosis. The purpose of this manuscript is to review the advances in the diagnosis and management of cardiac amyloidosis with the aim of educating colleagues who provide care in the primary care setting. We have summarized the pathogenesis of amyloidosis, its association with plasma cell dyscrasias, novel diagnostic and surveillance approaches including echocardiography, cardiovascular magnetic resonance imaging, histopathologic techniques, systemic biomarkers, and advanced treatment approaches including supportive symptomatic management and standard of care chemotherapy targeting the amyloid deposits. Given the overall poor prognosis of amyloidosis, we have also discussed the role of palliative and hospice care.

Fluoroquinolones and the Risk of Aortopathy: A Systematic Review and Meta-Analysis.

INTRODUCTION: Recent studies have raised concerns that fluoroquinolone use is associated with an increased risk of aortopathy, including aortic aneurysm with and without dissection. OBJECTIVE: We performed a meta-analysis with a comprehensive literature review to further investigate this association. METHODS: This analysis was conducted per PRISMA guidelines. PubMed, Cochrane Library, ClinicalTrials.gov, Embase, Web of Science, and Google Scholar were searched for studies that included adult patients (age >18 years) exposed to fluoroquinolones or control antibiotics (amoxicillin/any other antibiotic) for urinary tract infection or pneumonia with a primary outcome of aortic aneurysm or dissection. Heterogeneity was calculated using Q statistic I2 . RESULTS: A total of 6 studies-comprised of 59% males-were included in our analysis, which showed an increased combined risk of development of aortic aneurysm and aortic dissection with quinolone exposure when compared with controls (relative risk [RR] = 2.11; 95% CI, 1.62 - 2.75; I2 = 83.700). Individual relative risk for aortic aneurysm (RR = 2.83; 95% CI, 2.02 - 3.95, I2 = 89.150) and aortic dissection (RR = 1.99; 95% CI, 1.23 - 3.06; I22 = 71.33) also were significantly increased. CONCLUSION: Compared to other antibiotics, the use of fluoroquinolones was associated with a significantly higher risk of aortic aneurysm and dissection combined.

Atrial fibrillation and cancer; understanding the mysterious relationship through a systematic review.

BACKGROUND: Atrial Fibrillation (AFib) is the most common cardiac arrhythmia, occurring in ≈1% of the general population. An increased risk of malignancy among patients with AFib would be of substantial public health importance, given the high prevalence and associated economic burden of both disorders. OBJECTIVES: To evaluate the relationship between atrial fibrillation (AFib) and cancer. METHODS: We conducted an extensive database search on PubMed, Google Scholar, ScienceDirect, and SEER Database from their inception to September 2019 for any study that evaluated the association between AFib and cancer. RESULTS: In the first 3 months of AFib diagnosis, Ostenfeld et al. reported an absolute cancer risk of 2.5% with a standardized incidence ratio of 7.02 and 3.53 for metastatic and localized cancer, respectively. Likewise, Saliba et al. detected an increase in the odds of cancer diagnosis in first 90 days after AF diagnosis with OR of 1.85. Moreover, in another study new-onset breast and colorectal cancer was especially associated with AF in the first 90 days after diagnosis with HR of 3.4 but not thereafter (HR 1.0). Similarly, Conen et al. reported high relative risk of cancer with HR of 3.54 in the first 3 months after new-onset AFib. However, beyond the initial 90 day period, the risk of cancer in AFib is only slightly increased. CONCLUSION: Based on our review, there appears to be an increase in risk of subsequent diagnosis of cancer in patients with AF, likely owing to the shared risk factors between the two conditions. While the results of this study raise interesting questions for future search, they are not currently strong enough to justify initiating cancer screening for an occult cancer in a patient with AF. Regardless, measures to target modification of these shared risk factors remains an important consideration.

Obstructive sleep apnea and peripheral vascular disease: a systematic review based on current literature.

INTRODUCTION: Obstructive sleep apnea (OSA) is an established risk factor for poor cardiovascular outcomes and coronary artery disease, but its influence on the development of peripheral artery disease (PAD) is not well established. The aim of our study was to understand the mutual prevalence of OSA and PAD and any reported statistical association between the two conditions. METHODS: PubMed, Ovid Embase, Web of Science, Cochrane library and clinicaltrials.gov databases were systematically searched up to 29 November 2018. A total of 844 articles were identified and 744 articles were screened for relevance. RESULTS AND CONCLUSION: Eleven prospective cohorts qualified for inclusion with N = 63,642 (M = 28,062, F = 35,494). All studies evaluated OSA severity primarily with apnea-hypopnea index (AHI) values. The overall prevalence of PAD was 20.5% (N = 13,068). Except for two studies, all studies reported an increased prevalence of OSA in patients with PAD. OSA severity was not found to have an association with poor ankle brachial index values or increasing daytime sleepiness as measured by Epworth sleepiness scale. Further prospective clinical trials are required to further delineate this finding.

Reversible bradycardia secondary to myxedema coma: case-report.

Myxedema coma occurs mostly in patients with long-standing untreated or undertreated hypothyroidism. Bradycardia is a well-known cardiac manifestation for myxedema coma; however, not all bradycardia with hypothyroidism are sinus bradycardia. Sick sinus syndrome is a group of arrhythmias caused by the malfunction of the natural pacemaker of the heart. Tachy-Brady syndrome is considered to be a type of sick sinus syndrome, where the heart alternates between tachycardia and bradycardia, and it is usually treated with pacemaker implantation along with rate slowing medical therapy. Here we report a case of an 83-year-old female who presented with myxedema coma and atrial fibrillation with tachycardia and intermittent slow ventricular response. We attempt to review the relationship between these two diseases and conclude that appropriate diagnosis of myxedema coma, may be beneficial in reducing the need for pacemaker implantation.

Controls on species distribution and biogeochemical cycling in nitrate-contaminated groundwater and surface water, southeastern Australia.

A detailed study of groundwater and surface water nitrate over four seasons across an area of varied landuse provided insights into the mechanisms that underlie accumulation and transport of nitrate. High nitrate concentrations found in a significant percentage of surface water and shallow groundwater samples are due to anthropogenic contamination. Statistics (PCA, ANOVA, parsimonious model and general linear regression) were used to explore the relationship between NO3- and land use, and confirmed that areas of high NO3- concentration are associated with dairy pasture and horticulture. Seasonally, NO3- levels are greater during winter, the wettest part of the year. Values of δ15N showed that most nitrate is sourced from livestock waste, with a smaller contribution from synthetic fertilizer. Direct wash-off of animal waste from dairy farms results in higher NO3- concentrations in surface water than in groundwater. Denitrification is an important NO3- attenuation mechanism which reduces NO3- to NH4, as demonstrated by the PCA analysis, which showed positive correlation of NO3- concentrations with dissolved oxygen and negative correlations with NH4+, Fe2+and Mn2+; the latter two species may act as the electron donors necessary for reduction of NO3-. The often high NO3- concentrations in shallow groundwater are decreased by denitrification, which can occur at relatively shallow depths (<3 m). The relatively small NO3- concentrations in deeper groundwater are due partly to denitrification, but more to originally lower NO3- concentrations, as the age of deeper groundwater shows that it was recharged before agriculture was established in the study area. Overall, the study demonstrates the usefulness of hydrogeochemical characterisation and multivariate statistics in the evaluation of impacts of agricultural land-use on regional N cycling. In particular, the results show that efforts to mitigate NO3- pollution from farms should concentrate more on wash-off of animal waste than the contribution of nitrogenous synthetic fertilizer.

Percutaneous coronary intervention for chronic total occlusion in patients aged <75 years versus ≥75 years: a systematic review.

Objective: To examine the effect of age on procedural and clinical outcomes in patients undergoing percutaneous coronary intervention (PCI) of chronic total occlusion (CTO) lesions. Methods: Literature search was conducted across PubMed, Google Scholar and Web of science, databases till March 2019. Results: Seven studies including 7671 patients with an overall follow-up period of 1.5 to 5 years were included in our review. A total of 6299/1372 patients were included in non-elderly and elderly groups, respectively, with mean age and 67%/61% male patients. CTO-PCI was similarly successful in younger and older patients (82.8%, n = 5070 vs. 78.1%, n = 1010). The incidence of short-term outcomes was low across the studies and comparable between the two groups (all-cause mortality: 0.4% younger vs. 0.85% elderly, cerebrovascular accidents: 0.3% vs. 0.4%, major adverse cardiovascular events (MACE): 1.53% vs. 3.72% and major bleeding: 0.57% vs. 2.18%). Long-term outcomes including all-cause mortality (8.89% vs. 29.5%), cardiac mortality (3.72% vs. 15%) and MACE (24.9% vs. 40%) occurred with a higher incidence in elderly patients. When results were segregated according to the success of CTO-PCI, reduced clinical events were noted with successful revascularization in either age group. Conclusion: Compared with the younger age group, CTO-PCI in elderly patients is safe and feasible with a comparable incidence of short-term outcomes. In either population, the incidence of long-term outcomes including survival remains a concern but when successful, CTO-PCI may be associated with improvement in terms of multiple patient-important clinical end-points.

A Case of Amitriptyline-induced Myocarditis.

Amitriptyline is a widely prescribed tricyclic antidepressant (TCA) with a very concerning cardiotoxicity profile, but it is one that has not been discussed much in literature. Here, we present a case of amitriptyline toxicity presenting as myocarditis with pericardial involvement. A 21-year-old male with no previous cardiac history presented to the emergency department (ED) with a decreased level of consciousness after an amitriptyline overdose as a suicidal attempt. For concerns with airway protection, the patient was intubated and subsequently admitted to the intensive care unit (ICU). An electrocardiogram (EKG) showed sinus tachycardia, prolonged QRS complex, prolonged QTc interval, and nonspecific ST-T wave changes. Intravenous fluid resuscitation and sodium bicarbonate were administered with a target blood pH of 7.5 to 7.55. Two days later, the patient was taken off mechanical ventilation and improved clinically. However, troponin levels began to rise with a peak level of 4.08 µg/L. He then began having fevers, elevated white blood cell counts (WBCs), and elevated inflammatory markers. Transthoracic echo (TTE) revealed an ejection fraction (EF) of 45%-50%, no wall segment motion abnormalities, and a mild-to-moderate pericardial effusion. Cardiac magnetic resonance (CMR) was done, which revealed changes indicative of acute myocarditis, moderate pericardial effusion, a calculated EF of 45% with a moderate left ventricular dilation, and no coronary artery stenosis or anomalous coronary artery origin. Given the patient's age, the absence of cardiac risk factors, and the presence of an amitriptyline overdose along with his EKG, TTE, and CMR findings, we hypothesize that this myocarditis with pericardial involvement is due to amitriptyline-induced direct toxicity.

Influence of Left Ventricular Hypertrophy on In-Hospital Outcomes in Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

Left ventricular hypertrophy (LVH) is associated with worse outcomes in chronic obstructive pulmonary disease (COPD); however, its role in an acute exacerbation of COPD (AECOPD) has not been reported. This was a retrospective cohort study during 2008-2012 at an academic medical center. AECOPD patients >18 years with available echocardiographic data were included. LVH was defined as LV mass index (LVMI) >95 g/m2 (women) and >115g/m2 (men). Relative wall thickness was used to classify LVH as concentric (>0.42) or eccentric (<0.42). Outcomes included need for and duration of non-invasive ventilation (NIV) and mechanical ventilation (MV), NIV failure, intensive care unit (ICU) and total length of stay (LOS), and in-hospital mortality. Two-tailed p < 0.05 was considered statistically significant. Of 802 patients with AECOPD, 615 patients with 264 (42.9%) having LVH were included. The LVH cohort had higher LVMI (141.1 ± 39.4 g/m2 vs. 79.7 ± 19.1 g/m2; p < 0.001) and lower LV ejection fraction (44.5±21.9% vs. 50.0±21.6%; p ≤ 0.001). The LVH cohort had statistically non-significant longer ICU LOS, and higher NIV and MV use and duration. Of the 264 LVH patients, concentric LVH (198; 75.0%) was predictive of greater NIV use [82 (41.4%) vs. 16 (24.2%), p = 0.01] and duration (1.0 ± 1.9 vs. 0.6 ± 1.4 days, p = 0.01) compared to eccentric LVH. Concentric LVH remained independently associated with NIV use and duration. In-hospital outcomes in patients with AECOPD were comparable in patients with and without LVH. Patients with concentric LVH had higher NIV need and duration in comparison to eccentric LVH.

A patient selection score for cardiac resynchronization therapy.

BACKGROUND: We hypothesized a patient selection score (PSS) may improve patient selection for cardiac resynchronization therapy (CRT). METHODS: Of 136 patients who received CRT, group A included 100 study patients and group B 36 patients for validation. A positive response to CRT was a left ventricular (LV) end-systolic volume decrease of ≥15% and survival from heart failure at end of follow-up. RESULTS: Of 100 group A patients, 37 (37%) were CRT responders during 14-month follow-up. A 7-point PSS was generated based on six variables. The cutoff point for PSS to predict a positive response to CRT was >4 by receiver operating characteristic (ROC) analysis. The area under the ROC curve (AUC) for PSS to predict CRT response was 0.94 (P = 0.0001). CRT responders in patients with a PSS > 4 and ≤4 were 33/40 (83%), and 4/60 (7%), respectively (P < 0.001). Multivariate Cox proportional regression analysis showed that PSS was related to CRT response (hazard ratio = 10.3, P < 0.0001). The CRT response rate in patients with a PSS > 4 in Group B was also significantly higher compared to a PSS ≤ 4 (88% vs. 16%, P < 0.001). The AUC for PSS to predict a CRT response in Group B was 0.91 (P = 0.0001). CONCLUSIONS: Patients with a PSS >4 are the most likely to respond to CRT. Using this score system, a PSS score >4 can predict the probability of a CRT response up to 88% in patients with heart failure and a wide QRS duration.

Impact of left atrial volume in prediction of outcome after cardiac resynchronization therapy.

UNLABELLED: Left atrial volume index (LAVI) as a predictor of mortality has not been well investigated in patients with cardiac resynchronization therapy (CRT). The purpose of this study is to evaluate the impact of LAVI in predicting mortality in CRT patients. METHODS: We studied 100 consecutive patients who received CRT (male 73, age 69.9 ± 9.6 years). The follow-up duration of all echocardiographic measurements was 14.4 ± 10.5 months after CRT. LAVI was measured from apical views on two-dimensional echocardiography by bi-plane rule. A decrease of left ventricular end systolic volume ≥ 15% after CRT was defined as a positive response to CRT. RESULTS: The mean LAVI at baseline was 59.9 ± 22.7 ml/m(2). LAVI in patients who died (78.2 ± 27.5 ml/m(2)) was significantly greater than those who survived (55.9 ± 19.5 ml/m(2), p<0.0001) during follow-up of 17 ± 10.6 months. The area under ROC curve (AUC) for LAVI predicting death was 0.77 (p=0.0001). The cutoff point for LAVI predicting death was LAVI>59.4 ml/m(2). LAVI>59.4 ml/m(2) was related to mortality by Cox proportional univariate regression [hazard ratio (HR)=5.15, 95% CI=1.48-17.93, p=0.01]. After adjustment for the variables with significant difference by univariate regression, LAVI>59.4 ml/m(2) was continuously related to mortality by multivariate regression (HR=4.56, 95% CI, 1.30-15.97, p=0.02). LAVI>59.4 ml/m(2) was associated with a near 5-fold increase in mortality during follow-up of 17 ± 10.6 months. CONCLUSION: Patients who have LAVI>59.4 ml/m(2) continue to have increased mortality despite CRT.

Thoracic aortic atheroma severity predicts high-risk coronary anatomy in patients undergoing transesophageal echocardiography.

INTRODUCTION: We hypothesized a relationship between severity of thoracic aortic atheroma (AA) and prevalence of high-risk coronary anatomy (HRCA). MATERIAL AND METHODS: We investigated AA diagnosed by transesophageal echocardiography and HRCA diagnosed by coronary angiography in 187 patients. HRCA was defined as ≥ 50% stenosis of the left main coronary artery or significant 3-vessel coronary artery disease (≥ 70% narrowing). RESULTS: HRCA was present in 45 of 187 patients (24%). AA severity was grade I in 55 patients (29%), grade II in 71 patients (38%), grade III in 52 patients (28%), grade IV in 5 patients (3%), and grade V in 4 patients (2%). The area under receiver operating characteristic curve for AA grade predicting HRCA was 0.83 (p = 0.0001). The cut-off points of AA to predict HRCA was > II grade. The sensitivity and specificity of AA > grade II to predict HRCA were 76% and 81%, respectively. After adjustment for 10 variables with significant differences by univariate regression, AA > grade II was related to HRCA by multivariate regression (odds ratio = 7.5, p< 0.0001). During 41-month follow-up, 15 of 61 patients (25%) with AA >grade II and 10 of 126 patients (8%) with AA grade ≤ 2 died (p= 0.004). Survival by Kaplan-Meier plot in patients with AA > grade II was significantly decreased compared to patients with AA ≤ grade II (p= 0.002). CONCLUSIONS: AA > grade II is associated with a 7.5 times increase in HRCA and with a significant reduction in all-cause mortality.

Electrocardiographic abnormalities of takotsubo cardiomyopathy in a patient with paced ventricular rhythm.

Takotsubo cardiomyopathy (TCM) is a unique cardiomyopathy characterized by chest pain, ECG, and regional wall motion abnormalities closely mimicking acute myocardial infarction, in the absence of significant coronary artery disease. Classic ECG changes of TCM include ST elevation or T wave inversion. However, ECG abnormalities of TCM in patients with paced ventricular rhythms have not been well characterized. Herein, we report the case of an 85-year-old pacemaker dependant female who was diagnosed with TCM four weeks following the demise of her husband. Abnormal negative T wave concordance in precordial leads and QT interval prolongation were the only new ECG findings and these reverted back to baseline on followup.

Evaluation of left ventricular dyssynchrony using combined pulsed wave and tissue Doppler imaging.

INTRODUCTION: The combination of pulsed wave (PW) and tissue Doppler imaging (TDI) has been proposed as a new method to assess left ventricular (LV) mechanical dyssynchrony (LVMD), but results have not been validated. We investigated the correlation of a combination of PW and TDI with a positive response to cardiac resynchronization therapy (CRT). MATERIAL AND METHODS: We studied 108 consecutive patients who received CRT. Patients with atrial fibrillation were excluded. The time difference (T(PW-TDI)) between onset of QRS to the end of LV ejection by PW (T(PW)) and onset of QRS to the end of the systolic wave in LV basal segments with greatest delay by TDI (T(TDI)) was measured before CRT and during short-term and long-term follow-up. RESULTS: The T(PW-TDI) interval before CRT was 74 ±48 ms. Intra-observer variabilities for T(PW) and T(TDI) were 1.5 ±0.24% and 1 ±0.17%. Inter-observer variabilities for T(PW) and T(TDI) were 1 ±0.36% and 1 ±0.64%, respectively. T(PW-TDI) > 50 ms was defined as the cutoff value for diagnosis of LVMD by receiver operating curve (ROC) analysis. During follow-up of 15 ±11 months, the sensitivity and specificity of TP(PW-TDI) to predict a positive response to CRT were 98% and 82%, respectively. The area under the ROC curve was 0.92. There was a significant agreement between LVMD determined by T(PW-TDI) and the positive response to CRT (κ=0.80). CONCLUSIONS: Left vertricular dyssynchrony detected by the method combining PW and TDI demonstrated a high reproducibility, sensitivity, specificity and agreement with a positive response to CRT.

Left Atrial Volume and Post-Operative Atrial Fibrillation after Aortic Valve Replacement.

Post-operative atrial fibrillation (POAF) after valve surgery is associated with increased morbidity and mortality. Risk factors identified in the past to predict POAF are of moderate accuracy. We performed a retrospective analysis of 139 patients undergoing aortic valve replacement for aortic stenosis. Post-operative AF occurred in 44% of the patients. In multivariate analysis only left atrial volume (LAV) index was a predictor of POAF. A LAV index of >46 cc/m2 predicted POAF with a sensitivity and specificity of 92% and 77%. We propose that LAV index can be used preoperatively to identify patients at risk for POAF to target preventive interventions. Background: Post-operative atrial fibrillation (POAF) is common after valve surgery and is associated with increased morbidity and mortality. Many of the previously identified predictors of POAF are of moderate accuracy. Left atrial volume (LAV) index has been proposed in the past as a predictor of POAF in patients undergoing cardiac surgery. In patients with aortic stenosis (AS), increased LAV is a marker of severity of stenosis. Hypothesis: Left atrial volume index is a very good predictor of POAF in patients undergoing aortic valve replacement (AVR) for AS. Methods: We performed a retrospective analysis of 139 consecutive patients with no previous atrial fibrillation (AF) undergoing AVR for AS in our center. Results: Post-operative AF occurred in 44% of patients. Patients with POAF had a longer hospital stay compared to patients without (12 vs 8 days; p < 0.001). In univariate analysis, age (p = 0.046), aortic valve area (p = 0.005) and LAV index (p < 0.001) were significant predictors of POAF. In multivariate analysis only LAV index (R2= 0.58; p < 0.001) predicted POAF. A LAV index > 46ml/m2 predicted POAF with a sensitivity and specificity of 92% and 77% respectively. Moreover, there was a significant increase in the incidence of POAF with increasing quartiles of LAV index, supporting causality. Conclusion: Left atrial volume index is an excellent predictor of POAF in patients undergoing AVR for AS. It can be used for selecting patients who are at a high risk for developing POAF to target preventive interventions.

Effect of medical therapy on left ventricular ejection fraction in patients with systolic heart failure and narrow QRS duration with and without ischemic heart disease and left ventricular mechanical dyssynchrony.

We studied 99 consecutive patients with class III-IV systolic heart failure with a left ventricular ejection fraction (LVEF) < or =35% and a QRS duration <120 milliseconds. Patients with cardiac resynchronization therapy were excluded. Echocardiography was performed in all patients before and after optimal standard heart failure therapy. The septal-to-posterior wall motion delay (SPWMD) > or =130 milliseconds on echocardiogram was defined as left ventricular mechanical dyssynchrony (LVMD). Sixty-nine of 99 patients (70%) had ischemic heart disease. During follow-up of 15.2 +/- 9.8 months, LVEF improvement > or =15% was greater patients in nonischemic group (50%, 15/30) than in ischemic group (9%, 6/69; P < 0.001). After adjustment for age, gender, and clinical and echocardiographic characteristics, ischemic heart disease and grade of coronary disease were persistently related to LVEF improvement > or =15% (P = 0.03 and 0.02, respectively). Twenty of 99 patients (20%) had SPWMD > or =130 milliseconds (LVMD group), and 79 of 99 patients (80%) had SPWMD <130 milliseconds (non-LVMD group). LVEF increased in both groups (P = 0.005) during follow-up, but the percentage of patients with LVEF improvement > or =15% in LVMD was greater compared with patients without LVMD (40% versus 16%, respectively, P = 0.03). In conclusion, the improvement of LVEF in patients with systolic heart failure and narrow QRS was greater in patients with nonischemic heart disease and LVMD compared with patients with ischemic heart disease and absence of LVMD during medical therapy without cardiac resynchronization therapy.