Life-Threatening Reaction to Lifesaving Medication: Stepwise Approach to Severe Adverse Reactions to PCSK-9 Monoclonal Antibodies.

Typical side effects of proprotein convertase subtilisin/kexin type 9 monoclonal antibodies including influenza-like illness and injection site reactions, are minor and well tolerated. This case, however, highlights a less common but severe reaction, indicating the need for clinicians to understand and manage potential rare side effects noted with biologics.

Advances in targeting LDL cholesterol: PCSK9 inhibitors and beyond.

There is a direct relationship between the duration and level of exposure to low density lipoprotein cholesterol (LDL-C) levels over one's lifespan and cardiovascular events. Early treatment to lower elevated LDL-C is crucial for better outcomes with multiple therapies currently available to reduce atherogenic lipoproteins. Statins remain the foundation of LDL-C lowering therapy as one of the most cost-effective drugs to reduce atherosclerotic events (ASCVD) and mortality. Nonetheless, LDL-driven goal attainment remains suboptimal globally, highlighting a considerable need for non-statin therapies to address residual risk related to statin intolerance, non-adherence, and inherited lipoprotein disorders. LDL-C lowering interventions beyond statins include ezetimibe, PCSK9 monoclonal antibodies, inclisiran and bempedoic acid with specific guideline recommendations as to when to consider each. For patients with homozygous familial hypercholesterolemia requiring more advanced therapy, lomitapide and evinacumab are available, providing mechanisms that are not LDL receptor dependent. Lipoprotein apheresis remains an effective option for clinical familial hypercholesterolemia as well as elevated lipoprotein (a). There are investigational therapies being explored to add to our current armamentarium including CETP inhibitors, a third-generation PCSK9 inhibitor (small recombinant fusion protein oral PCSK9 inhibitor) and gene editing which aims to directly restore or disrupt genes of interest at the DNA level. This article is a brief review of the pharmacotherapy options beyond statins for lowering LDL-C and their impact on ASCVD risk reduction. Our primary aim is to guide physicians on the role these therapies play in achieving appropriate LDL-C goals, with an algorithm of when to consider each based on efficacy, safety and outcomes.

The impact of sex, body mass index and chronic kidney disease on outcomes following percutaneous coronary intervention.

OBJECTIVE: This study sought to evaluate 1) the relationship between body mass index (BMI), chronic kidney disease (CKD) and bleeding complications in patients undergoing percutaneous coronary intervention (PCI); and 2) whether CKD modified the effect of BMI on major bleeding and major adverse cardiac and cerebrovascular events (MACCE). BACKGROUND: The interaction of CKD, sex and BMI in patients undergoing PCI is unclear. METHODS: Between 2010 and 2018, a total of 31,116 patients underwent PCI at six New York metropolitan area hospitals. Bleeding complications were classified by the Bleeding Academic Research Consortium (BARC). Major bleeding was defined as BARC≥3. MACCE was the composite of in-hospital death; myocardial infarction; cerebrovascular events and major bleeding complications. Interaction on multiplicative scales was assessed adjusting for other factors. A three-way multiplicative interaction between BMI, CKD and sex were considered and evaluated for both endpoints of primary interest (BARC≥3 and MACCE). RESULTS: Patients with BARC≥3 bleeding were older (p < 0.0001) and more likely female (p < 0.0001). A 3-way interaction existed between sex, BMI, and CKD on BARC≥3 (p = 0.02). Specifically, the effect of CKD status on odds of BARC≥3 depended on BMI group among males, whereas BMI did modify the relationship between CKD and BARC≥3 among females; after stratification by sex, a significant interaction between BMI and CKD was present in females (p = 0.03) but not in males (p = 0.43). Among females without CKD, normal BMI patients had the greatest odds of BARC≥3 compared to obese or overweight females. Contrasted to females without CKD, among females with CKD there was no significant increased odds of BARC≥3 in normal BMI patients compared to obese or overweight females. However, overweight females with CKD had a significantly increased odds of BARC≥3 compared to obese females with CKD. Furthermore, obese females with CKD had significantly greater BARC≥3 odds compared to obese females without CKD. Similarly, overweight females with CKD had an increased odds of BARC≥3 compared to overweight females without CKD. No significant interactions were found for the odds of MACCE. CONCLUSION: In patients undergoing PCI, there was evidence of a significant and complex 3-way interaction between BMI, CKD and sex for major bleeding events. The predicted probability of major bleeding was greater for females than for male patients, and for both sexes, greater among those with CKD, but BMI group influences these probabilities. Obese females with kidney disease had the lowest incidence of bleeding complications when compared with overweight or normal weight female patients undergoing PCI. This interaction was not seen in the male group or for MACCE. Furthermore, age, cardiogenic shock, STEMI and use of IABP/Impella were each independently associated with odds of major bleeding (among both males and females) and MACCE.

Percutaneous coronary intervention with Impella support with and without intra-aortic balloon in cardiogenic shock patients.

OBJECTIVE: To assess the clinical characteristics and in-hospital bleeding complications and major adverse cardiac and cerebrovascular events (MACCE) associated with the use of Impella alone or the combination of an intra-aortic balloon pump (IABP) with Impella in cardiogenic shock (CS) patients undergoing percutaneous coronary intervention (PCI). METHODS: All CS patients who underwent PCI and were treated with an Impella mechanical circulatory support (MCS) device were identified. Patients were divided into two groups: having MCS support with Impella alone or with both, IABP and Impella simultaneously (dual MCS group). Bleeding complications were classified by a modified Bleeding Academic Research Consortium (BARC) classification. Major bleeding was defined as BARC≥3 bleeding. MACCE was the composite of in-hospital death, myocardial infarction, cerebrovascular events and major bleeding complications. RESULTS: Between 2010 and 2018 a total of 101 patients were treated at six tertiary care New York hospitals with either Impella (n = 61) or dual MCS with Impella and IABP (n = 40). Clinical characteristics were similar for both groups. Dual MCS patients presented more often with a STEMI (77.5 % vs. 45.9 %, p = 0.002) and had left main coronary artery intervention (20.3 % vs. 8.6 %, p = 0.03). Major bleeding complications (69.4 % vs. 74.1 %, p = 0.62) and MACCE rates (80.6 % vs. 79.3 %, p = 0.88) were very high but similar in both groups, however access site bleeding complications were lower in patients treated with dual MCS. In-hospital mortality was 29.5 % for the Impella group and 25.0 % for the dual MCS group (p = 062). Access site bleeding complications were lower in in patients treated with dual MCS (5.0 % vs. 24.6 %, p = 0.01). CONCLUSION: In CS patients undergoing PCI with either the Impella device alone or with Impella and IABP, major bleeding complications and MACCE rates were high but not significantly different between the two groups. In hospital mortality was relatively low in both MCS groups despite the high-risk characteristics of these patients. Future studies should assess the risks and benefits of the simultaneous use of these two MCS in CS patients undergoing PCI.

Prevalence and clinical significance of arrhythmias during labour in women with structurally normal hearts.

OBJECTIVES: Examine the association between arrhythmias and adverse maternal outcomes in women with structurally normal hearts. METHODS: This was a case-control study of women admitted in labour to one of eight hospitals of Northwell Health from January 2015 to June 2021. After excluding women with structurally abnormal hearts, we identified women with an arrhythmic event and randomly subsampled the rest of the cohort to create a control group of 1025 patients. Multivariate analysis was performed to examine the association between arrhythmias and the incidence of caesarean section (CS), preterm labour (PTL), admission to the neonatal intensive care unit and longer length of stay (LOS). RESULTS: Of 1 41 769 women admitted in labour with a structurally normal heart, 137 had at least one arrhythmic event (0.097%). Supraventricular tachycardia (SVT), atrial fibrillation/flutter (AF) and frequent premature ventricular complexes or non-sustained ventricular tachycardia (VA) were present in 65 (0.046%), 22 (0.016%) and 46 (0.032%) women, respectively. Arrhythmia was previously diagnosed in 58.0% SVT cases but only in 9.7% AF and 8.1% VA cases. After adjusting for age, parity and comorbidities, the presence of any arrhythmia was an independent predictor of CS (OR 1.7 95% CI 1.2 to 2.5), PTL (OR 1.8, CI 1.1 to 3.0) and LOS (mean ratio 1.6, CI 1.4 to 1.8). This association was driven by presence of SVT and AF, whereas VAs were not associated with adverse outcomes. CONCLUSIONS: Arrhythmias, specifically SVT and AF, during labour in women with structurally normal heart are independently associated with adverse obstetrical outcomes.

Clinical significance of unexplained persistent sinus tachycardia in women with structurally normal heart during the peripartum period.

BACKGROUND: Persistent sinus tachycardia (ST) is frequently encountered during pregnancy and peripartum period and its etiology often remains elusive. We sought to examine the possible association between unexplained persistent ST and obstetric outcomes. METHODS: A case control study was conducted using chart review of women admitted in labor to one of 7 hospitals of Northwell Health between January 2015 to June 2021. After excluding women with structurally abnormal hearts, we identified patients with persistent ST during the peripartum period, defined as a heart rate of more than 100 bpm for more than 48 h. A control group was created by randomly subsampling those who did not meet the inclusion criteria for sinus tachycardia. Obstetric outcomes were measured as mother's length of stay (LOS), pre-term labor (PTL), admission to the neonatal ICU (NICU), and whether she received cesarean-section (CS). RESULTS: Seventy-eight patients with persistent ST were identified, out of 141,769 women admitted for labor throughout the Northwell Health system. 23 patients with ST attributable to infection or hypovolemia from anemia requiring transfusion and 55 with unclear etiology were identified. After adjusting for age and parity, pregnant mothers with ST were 2.35 times more likely to have a CS than those without (95% CI: 1.46-3.81, p = 0.0005) and had 1.38 times the LOS (1.21- 1.56, p < 0.0001). Among mothers with ST, those with unexplained ST were 2.14 times more likely to have a CS (1.22-3.75, p = 0.008). CONCLUSION: Among pregnant patients, patients with ST have higher rates of CS.This association is unclear, however potential mechanisms include catecholamine surge, indolent infection, hormonal fluctuations, and medications. More studies are needed to explore the mechanism of ST in pregnant woman to determine the clinical significance and appropriate management.

A Peculiar Case of Fentanyl-Induced Cardiomyopathy.

An alarming rise in prescription and non-prescription misuse of opioids has been observed recently, leading to potentially devastating consequences. Opioid misuse contributes to cardiac risk burden and can cause diseases such as acute coronary syndrome, congestive heart failure, arrhythmias, QTc prolongation, and endocarditis. Here, we describe the case of a 35-year-old male with recreational fentanyl use who was found to have a cardiogenic shock on point-of-care ultrasound (POCUS), likely due to fentanyl-induced cardiomyopathy. Opioid-induced cardiomyopathy without any underlying cardiac disease in an adult appears to be a rare case. Our case highlights the importance of promptly recognizing fentanyl toxicity, screening for possible cardiomyopathy secondary to its use, and emergent resuscitation with the maintenance of ventilation, diuretics, and vasopressor support. The use of the reversal agent, naloxone, is a crucial part of management.

A Case of Bundle Branch Re-entrant Ventricular Tachycardia 1 Year After Transcatheter Aortic Valve Replacement.

Bundle branch re-entrant ventricular tachycardia (VT) (BBR-VT) is a unique type of ventricular tachycardia often seen in patients with advanced heart diseases. Rarely, it is found in patients with a structurally normal heart. We describe a case of BBR-VT in a patient with normal ventricular function, a year after transcatheter aortic valve replacement (TAVR) for aortic stenosis. A 73-year-old man with a past medical history of non-obstructive coronary artery disease and severe aortic stenosis status post-TAVR with a 23-mm Sapien valve (Edwards Lifesciences, Irvine, CA, USA) about 1 year prior presented with palpitations and syncope. The electrocardiogram (ECG) showed a wide complex tachycardia with a left bundle branch block (LBBB) pattern and atrioventricular dissociation. The tachycardia was incessant and paroxysmal during 24-h telemetry monitoring. An electrophysiology study showed a normal A-H interval of 90 ms and a prolonged H-V interval of 84 ms with evidence of a split His. A hemodynamically stable VT was induced with a cycle length of 453 ms, which was identical to the clinical VT. This was diagnosed to be BBR-VT given the typical ECG pattern of LBBB, the presence of His inscription before each ventricular signal, and the H-H interval variation-predicted V-V variation when there was a wobble in tachycardia cycle length. Injury of the His-Purkinje system post-TAVR can provide the substrate for the development of BBR-VT. Current published literature shows early occurrence post-TAVR, but our case suggests that the timing between the index procedure and arrhythmia occurrence can be variable.

Delayed cardiac repolarisation as a predictor of in-hospital mortality in patients with COVID-19.

OBJECTIVE: With the rapid influx of COVID-19 admissions during the first wave of the pandemic, there was an obvious need for an efficient and streamlined risk stratification tool to aid in triaging. To this date, no clinical prediction tool exists for patients presenting to the hospital with COVID-19 infection. METHODS: This is a retrospective cohort study of patients admitted in one of 13 Northwell Health Hospitals, located in the wider New York Metropolitan area between 1 March 2020 and 27 April 2020. Inclusion criteria were a positive SARS-CoV-2 nasal swab, a 12-lead ECG within 48 hours, and a complete basic metabolic panel within 96 hours of presentation. RESULTS: All-cause, in-hospital mortality was 27.1% among 7098 patients. Independent predictors of mortality included demographic characteristics (male gender, race and increased age), presenting vitals (oxygen saturation <92% and heart rate >120 bpm), metabolic panel values (serum lactate >2.0 mmol/L, sodium >145, mmol/L, blood urea nitrogen >40 mmol/L, aspartate aminotransferase >40 U/L, Creatinine >1.3 mg/dL and glycose >100 mg/L) and comorbidities (congestive heart failure, chronic obstructive pulmonary disease and coronary artery disease). In addition to those, our analysis showed that delayed cardiac repolarisation (QT corrected for heart rate (QTc) >500 ms) was independently associated with mortality (OR 1.41, 95% CI 1.05 to 1.90). Previously mentioned parameters were incorporated into a risk score that accurately predicted in-hospital mortality (AUC 0.78). CONCLUSION: In the largest cohort of COVID-19 patients with complete ECG data on presentation, we found that in addition to demographics, presenting vitals, clinical history and basic metabolic panel values, QTc >500 ms is an independent risk factor for in-hospital mortality.