Citations

Introduction: Despite that trastuzumab (TZB) improves life expectancy and prognosis in patients with HER-2 positive breast cancer (BC), cardiotoxicity is a well-established complication. However, other potential cardiac complications of TZB such as pulmonary hypertension (PHTN) are poorly investigated. Aim: Evaluate the effect of TZB on pulmonary artery systolic pressure (PASP) and measure the predictors of developing elevated PASP. Methods: The medical records for all females who received TZB treatment for confirmed HER-2 positive BC at King Hussein Cancer Centre in Jordan between 2014 - 2019 who had a documented normal PASP of ≤35 mmHg before treatment were evaluated. Results: A total of 436 patients with a mean age of 53±11 years were included. The leading comorbidities were hypertension and diabetes mellitus affecting 26.2% and 15.4% of the patients, respectively. 15.6% of the study’s population were active smokers. Prior to initiating TZB, 22.3% had left ventricular hypertrophy (LVH), 14.3% had mild tricuspid valve regurgitation (TR), 11.5% had pericardial effusion, and 4.8% had mild aortic valve regurgitation (AR).Of alarming significance, 24.8% of the patients had their PASP increased after one year. Patients who developed elevated PASP tend to be older (56.9 vs 51.3, P<0.001), had baseline mild TR (26.3% vs 10.3%, P<0.001), LVH (39.4% vs 17.6%, P<0.001), and mild AR (9.1% vs 3.7%, P=0.031).Multivariate analysis showed that the only predictors of elevated PASP are TR at baseline (OR 3.9; 95% CI 1.58-6.17, P=0.001), and age (OR 1.04; 95% CI 1.01-1.06, P=0.005). However, baseline LVH (OR 1.79; 95% CI 0.98-3.26, P=0.057), number of the TZB cycles (OR 0.93; 95% 0.85-1.02, P=0.152), and the total dose of TZB (OR 1; 95% CI 1-1, P=0.284) were non-significant predictors. At 1 year follow up, the mean total cumulative dose of TZB was 6.8±1.8 grams that were given at a mean of 15±3 cycles. Moreover, major events (heart failure exacerbation, pulmonary embolism, and acute coronary syndrome) were recorded in 3.9% of the patients and death occurred in 4.1%. Conclusions: Trastuzumab demonstrated an increase in the PASP in a considerable portion of the patients at 1-year interval with this elevation being substantially concerning due to being highly indicative of PHTN.

Introduction: Stress echocardiography (SE) is a common functional imaging modality used for the detection of symptomatic coronary artery disease (CAD). Currently, the interpretation of SE relies on sex-based comparators for reporting parameters, including exercise time and functional aerobic capacity. These parameters are based on the cisgender male and female populations but have not been studied among transgender (TG) patients. Thus, we sought to characterize the SE parameters among a group of TG women. Methods: We designed a case-control study of TG women who underwent a SE at the Mayo Clinic. Each TG patient was age-matched with 2 cis-males and 2 cis-females. Demographics, medical history, and SE data were extracted. Conditional logistic regression analysis was performed to compare the TG cohort with each cisgender cohort separately. Results: Among the 43 TG females (age 57.7±9 years, 94.9% white), the prevalence of CAD was less than in cis-males (p=0.013) but similar to cis-females. For SE parameters, TG females had higher resting heart rates than cis-males (median [Q1, Q3]: 80 [71,93] vs 70 [64, 77]; p=0.002). Double product (24816 [21156, 27864] vs 26864 [22444, 30660]; p=0.016), exercise time (7.3 minutes [6,9] vs 8.5 [7.2, 9.5]; p=0.041), and metabolic equivalents (8.2 [7, 10] vs 9.5 [8.2, 10.5]; p=0.018), were all lower in TG females than cis-males. Exercise ejection fraction was higher in the transgender cohort than in cis-females (70 [70, 75] vs 70 [65, 70]; p=0.007). There was no difference in functional aerobic capacity or in the rest or stress wall motion score indices among the groups. Finally, there was no difference in the prevalence of positive electrocardiogram or SE studies. Conclusion: In conclusion, we report for the first time SE profiles for TG females which display an overall distinct phenotype compared to cis-males and cis-females. Larger prospective studies are warranted to further define these parameters for the TG population.

Introduction: Cardiovascular complications are the main contributors towards morbidity and mortality in hemochromatosis. Iron overload can cause arrhythmias and heart failure (HF). There is a paucity of data on haemochromatosis and the burden of HF and its sequalae. Hypothesis: To determine characteristics of HF patients with and without haemochromatosis, and in-hospital outcomes (mortality, length of stay (LOS), mechanical circulatory support, and cardiac transplantation). Methods: Patients with HF, with and without hemochromatosis, were identified from the Nationwide Inpatient Sample Database. Results: Between 2016-2019, 2,940 (0.06%) of 4,823,994 HF patients had hemochromatosis. The hemochromatosis cohort was younger (mean age, 68 vs 71 years), predominantly men (63% vs 52%), White (77% vs 64%), and had less cardiovascular comorbidity burden (coronary artery disease (41% vs 51%), atrial fibrillation (45% vs 46%), hypertension (20% vs 24%), hyperlipidaemia (44% vs 53%), diabetes (42% vs 49%) and obesity (18% vs 25%), compared with HF patients without hemochromatosis (p<0.01 for all). However, hemochromatosis patients had a higher concomitant third degree atrio-ventricular block (1.2% vs 0.7%), ventricular tachycardia (7.8% vs 5.4%), ventricular fibrillation (0.5% vs 0.3%), chronic liver disease (24% vs 6%) and anemia (51% vs 37%) [p<0.01]. The hemochromatosis patients had a higher mean LOS (6.1 vs 5.4 days, p<0.01), need for mechanical circulatory support (0.9% vs 0.6%, p<0.01) and cardiac transplantation (0.2% vs 0.1%, p<0.01). Mortality (2.0% vs 2.7%, p=0.09) was comparable between the groups. Conclusion: Despite younger age and lower burden of cardiovascular comorbidities, patients with hemochromatosis had a higher burden of arrhythmias, need for mechanical circulatory support and cardiac transplantation and a higher LOS. This warrants the need to devise early management strategies for HF patients with hemochromatosis.

Introduction: Differentiating type 2 myocardial infarction (T2MI) from myocardial injury can be difficult. The presence of objective evidence of acute myocardial ischemia may facilitate the identification of high-risk T2MI patients. Methods: Retrospective, observational cohort post-hoc analysis of adult emergency department patients undergoing hs-cTnT measurement. Patients with ≥1 hs-cTnT>99th percentile were adjudicated following the Fourth Universal Definition of MI. Patients were categorized as “subjective T2MI” when ischemic symptoms were the lone criteria supporting T2MI, or “objective T2MI” when there was ≥1 objective clinical feature (electrocardiography, imaging, angiography) of acute myocardial ischemia. The primary outcome was mortality. Results: A total of 857 patients were included, amongst which 55 (6.4%) were classified as subjective T2MI, 36 (4.2%) as objective T2MI, and 702 (82%) as myocardial injury. Among objective T2MIs, the most common criteria were ischemic electrocardiographic changes (n=29). Median (IQR) maximum hs-cTnT were 24 (18, 43) ng/L in myocardial injury, 34 (19, 80) in subjective T2MI, and 74 (35, 237) in objective T2MI. Those with objective T2MI had a higher risk of mortality during the index presentation (17% vs. 1.7%, p<0.0001; HR 11.1 95% CI 3.7-33.4) and at 2-year follow-up (47% vs. 31%, p=0.04; HR 1.92, 95% CI 1.17-3.14) than those with myocardial injury (Figure). Objective T2MI had a higher mortality than subjective T2MI at index presentation (17% vs. 2.0%, p=0.01) and at 1- (25% vs. 9.1%, p=0.04) and 3-months (31% vs. 13%, p=0.04) follow-up. There were no mortality differences between subjective T2MI and myocardial injury. Conclusions: In patients diagnosed with T2MI, those with objective evidence of myocardial ischemia have significantly worse outcomes compared to those with myocardial injury and subjective T2MI. A more rigorous definition of T2MI might be a more effective way to define this important entity.

Background: There is a paucity of data regarding the temporal trends and outcomes of transcatheter aortic valve replacement (TAVR) among patients with prior coronary artery bypass graft (CABG) surgery. Methods: We queried the Nationwide Readmissions Database (2016-2019) for hospitalized patients who underwent TAVR using ICD-10 codes. We evaluated the trends and outcomes of TAVR among patients with versus without a history of prior CABG. Multivariable regression analysis was used to adjust for patients’ and hospitals' characteristics when comparing the study groups. The primary outcome was in-hospital mortality. Results: The final analysis included 173,274 admissions who underwent TAVR of whom 31,271 (18.3%) had a history of prior CABG. During the study years, there was a decrease in the proportion of patients with prior CABG among those undergoing TAVR (22.0% in 2016 vs. 16.2%, Ptrend=0.01), while there was no change in their in-hospital mortality rate (1.08% in 2016 vs. 1.25% in 2019, Ptrend= 0.43). Patients with prior CABG were younger and less likely to be women compared with those without prior CABG. On multivariable adjustment, In-hospital mortality was lower among the group with versus without prior CABG (adjusted odds ratio [aOR] 0.77; 95% confidence interval [CI] 0.65-0.91, p<0.01). Adjusted analysis showed lower rate of 90-day readmission (OR 0.95; 95%CI 0.90-0.98, p=0.01), and similar rate of ischemic stroke (aOR 0.89; 95%CI 0.76-1.03, p=0.89), permanent pacemaker (PPM) implantation (aOR 0.99; 95%CI 0.93-1.05, p=0.99). Among those with prior CABG, female gender, and chronic kidney disease ≥3 were independently associated with higher in-hospital mortality, and obesity was associated with lower in-hospital mortality. Conclusion: In this analysis, there was a decrease in the proportion of patients with prior CABG among those undergoing TAVR. TAVR among those with prior CABG was not associated with increased short-term mortality or PPM implantation.

Background: RCTs studying the effect of sodium-glucose co-transporter 2 inhibitors (SGLT2i) on cardiovascular (CV) risk factors and outcomes have been underpowered to assess patients with overweight or obesity, thus presenting the need for a meta-analysis. Methods: Electronic databases were queried up till February 2022 for RCTs comparing SGLT2i with placebo in patients with overweight (BMI ≥25 kg/m2) or obesity (BMI ≥30 kg/m2) - irrespective of diabetes status - with a follow-up of ≥24 weeks. Meta-analyses were performed using the generic inverse variance technique and a random-effects model. Results are presented as weighted mean differences (WMD) for continuous outcomes, and hazard ratios (HR) for dichotomous outcomes. Outcomes studied were: (i) weight; (ii) systolic BP; (iii) diastolic BP; (iv) heart rate; (v) HDL-C; (vi) LDL-C; (vii) major adverse cardiac events (MACE), i.e., composite of CV death, non-fatal myocardial infarction (MI) and non-fatal stroke; (viii) composite of heart failure hospitalization and CV death (HFH/CV death); (ix) mortality; (x) MI; and (xi) stroke. Results: Seventeen RCTs (47,649 patients) were included. Compared with placebo, SGLT2i significantly reduced weight (WMD: -2.32 kg [-2.77, -1.88]), HbA1c (WMD: -0.79 % [-0.98, - 0.61]) and systolic BP (WMD: -2.15 mm Hg [-3.08, - 1.22]). SGLT2i did not have a significant effect on diastolic BP (WMD: -0.55 mmHg [-1.51, 0.41]), heart rate (WMD: 0.08 bpm. [-0.21, 0.37]), HDL-C (WMD: 1.62 mmol l -1 [-0.21, 3.45]) or LDL-C (WMD: 0.53 mmol l -1 [-0.88, 1.94]). Amongst CV outcomes, SGLT2i reduced the risk of MACE (HR: 0.90 [0.81, 0.99]), HFH/CV death (HR: 0.82 [0.75, 0.90]), and mortality (HR: 0.85 [0.77, 0.94]). No effect was noted on stroke (HR: 0.99 [0.85, 1.26]) or MI (HR: 0.89 [0.77, 1.02]). Conclusions: In patients with overweight or obesity, SGLT2i produce a modest but significant reduction in weight, systolic BP and HbA1c. SGLT2i may also reduce the risk of MACE, HFH/CV death, and mortality.

BACKGROUND: Differentiation of wide QRS complex tachycardias (WCTs) into ventricular tachycardia (VT) and supraventricular wide QRS tachycardia (SWCT) through 12-lead electrocardiogram (ECG) interpretation is one of the most critical yet challenging tasks in clinical practice. Recent research highlights novel automated methods that successfully diagnose WCTs. We sought to directly compare the diagnostic efficacy of these novel automated WCT differentiation methods (i.e., WCT Formula, VT Prediction Model, and WCT Formula II) to traditional ECG interpretation approaches (i.e., Brugada and Vereckei aVR algorithms). METHODS: A collection of paired WCT and baselined ECGs were retrospectively analyzed. Next, an electrophysiologist blindly and prospectively applied the Brugada and Vereckei aVR algorithms. Separately, computerized measurements were used to apply the three automated WCT differentiation methods. The diagnostic performance of each method was then evaluated. RESULTS: 213 WCTs (111 VT and 102 SWCT) from 105 patients were analyzed. The WCT Formula demonstrated superior overall accuracy (84.7% vs. 64.8%), specificity (86.2% vs. 35.3%), positive predictive value (PPV) (85.7% vs. 60.7%), and positive (+) likelihood ratio (LR) (6.06 vs. 1.42) compared to Vereckei aVR algorithm. Similarly, the WCT Formula attained higher specificity (86.2% vs. 61.8%), PPV (85.7% vs. 71.9%), and (+) LR (6.06 vs. 2.36) than the Brugada algorithm. The WCT Formula II demonstrated superior overall accuracy (89.2% vs. 64.8%), specificity (84.3 % vs. 35.3%), PPV (86.7% vs. 60.7%), and positive (+) LR (5.97 vs.1.42) compared to Vereckei aVR algorithm as well as higher specificity (84.3 % vs. 61.8 %), PPV (86.7% vs. 71.9%), and (+) LR (5.97 vs. 2.36) than the Brugada algorithm. The VT prediction model yielded superior specificity (79.4% vs. 35.3%), PPV (79.8 vs. 60.7%) and (+) LR (3.63 vs.1.42) compared to the Vereckei aVR algorithm but did not demonstrate superior diagnostic performance to the Brugada algorithm. CONCLUSIONS: Novel automated WCT differentiation methods achieved similar or superior diagnostic performance metrics compared to traditional ECG interpretation approaches.

Introduction: Patients with a history of inflammatory bowel disease (IBD) are at a higher risk of atrial fibrillation (AF). There is a lack of evidence supporting catheter ablation in this group and predictors of procedural outcomes are unknown. Hypothesis: We assessed the hypothesis that patients with a history of IBD have worse procedural outcomes with more peri-procedural complications, especially in those whose disease is less well controlled. Methods: A single-center 1:1 propensity matched study of patients with no history of IBD and patients with IBD who underwent primary AF catheter ablation from January 2010 to December 2021 was conducted. The primary outcome was procedural efficacy defined by clinical AF recurrence and repeat catheter ablation. The secondary outcome was an assessment of safety looking at eight peri-procedural events. Univariate and multivariate binary logistic regression analysis was conducted to determine predictors of AF recurrence. Results: Our cohort was comprised of 94 patients, 47 patients with a history of IBD (mean age 64.7 ± 6.4 years) and 47 patients with no history of IBD (66.7 ± 7.1 years). Both groups had similar echocardiographic, baseline, and arrhythmia characteristics. All patients underwent pulmonary vein isolation and procedural endpoints were ascertained in all patients. At one-year post-ablation, the study group was statistically more likely to develop AF recurrence (OR 2.38, 95% CI 1.09 - 4.86, p=0.03) but were equally likely to undergo repeat catheter ablation (OR 2.56, 95% CI 0.62 - 10.6, p=0.19). Procedural safety was statistically similar in both groups. Four patients in the study group and three patients in the control group developed subcutaneous hematomas at the site of instrumentation (p=0.70). Multivariate analysis found pre-procedural c-reactive protein (CRP) (OR 1.04, 95% CI 1.00 - 1.12) and AF diagnosis to ablation time (OR 1.15, 95% CI 1.03 - 1.24) were independent predictors of post-procedure AF recurrence. Conclusions: Our study suggests patients with IBD are at a higher risk of developing AF recurrence after catheter ablation. Multivariate analysis showed CRP and AF diagnosis to time to ablation were both independent risk factors.

Introduction: COVID-19 pandemic has had an unprecedented impact worldwide, co-infections with neglected tropical diseases like Malaria can occur and affect the heart. Objective: Describe a unique case of Malaria and SARS CoV2 infection occurring concurrently with cardiac complications. Clinical Case: A 69-year-old male, retired canoeing athlete, with well-controlled arterial hypertension, presented odynophagia, cough, and dyspnea on slight exertion for 2 days. On examination, O2 saturation was 91%, blood pressure 100/60 mmHg, regular heart rate of 110 bpm, positive PCR for SARS-CoV-2, elevated D-Dimer, and chest X-ray with evidence of viral pneumonia. He received supplemental oxygen, steroids, and paracetamol. Two days later, he presented with choluria, afternoon episodes of high fever preceded by chills and myalgia, and a thick blood smear showed Plasmodium falciparum (PF) trophozoites. Antimalarial treatment was started with primaquine 15mg, 20 mg of artemether, and 120 mg of Lumefantrine daily with the disappearance of fever until day 14 of onset of symptoms when he presented with acute heart failure (AHF) with a reduced ejection fraction of 45%. NYHA Class IV, arterial hypotension, sudden onset palpitations, and afternoon febrile episode. The electrocardiogram showed atrial fibrillation (AF) with a rapid irregular ventricular response of 120 bpm; The echocardiogram revealed a 7mm circumferential pericardial effusion, right ventricular dysfunction. Treatment with colchicine, enoxaparin, spironolactone, and bisoprolol was started. A new thick smear demonstrated the persistence of PF. A new antimalarial regimen was restarted, with the disappearance of the fever 48 hours after its onset, with the reversion of AF to sinus rhythm. Discussion: A unique case of concurrent COVID-19 and Malaria, which cause challenges to the heart and lead to cardiovascular complications. Conclusion: An exceptional case is presented, the coexistence of SARS-CoV-2 and PF infection-associated complications of myocarditis, pericarditis, new-onset AF, and AHF. This interaction should not go unnoticed, physicians’ awareness is key, and early diagnosis and treatment can be lifesaving, mitigate and offer the best chance of cure.

Introduction: Arrhythmias commonly occur during clinical exercise stress testing (EST), however there are limited data on prognostic significance, particularly differences between individuals with minor versus significant arrhythmia burden. Hypothesis: We hypothesized that significant but not minor arrhythmia burden during EST would be predictive of future all-cause mortality. Methods: Adults who underwent clinically indicated EST at Mayo Clinic Rochester between September 1993 and April 2017 were included and followed-up until March 2021 using the National Death Index to ascertain survival status. Expert clinician coding pertaining to arrhythmia burden during EST were used to group individuals (see Table 1 ). Cox proportional hazard models adjusted for known predictors of exercise-induced arrhythmias, were used to test the association of arrhythmia burden with all-cause mortality. Results: A total of 30796 individuals were included (age: 55±14yrs; female: 36%; Table 1 ). Mean follow-up was 8.8±3.6yrs, with a total of 2516 deaths. Arrhythmia during EST was associated with all-cause mortality compared with no arrhythmia (HR: 1.72; 95% CI: 1.58-1.88; p<0.001), however significant arrhythmia showed greater association compared with minor arrhythmia (HR: 2.07; 95% CI: 1.81-2.38; p<0.001). Both minor and significant arrhythmia during EST were significant predictors of all-cause mortality compared with no arrhythmia ( Figure, Table 2 ), however, after model adjustments, only significant arrhythmia was associated with all-cause mortality (HR: 1.40; 95% CI: 1.21-1.63; p<0.001) ( Table 2 ). Conclusions: After multivariate adjustment, significant arrhythmia burden during EST showed a 40% increased future risk of all-cause mortality, Conversely, adjusting for age and sex attenuated the effect of minor arrhythmia burden during EST on incidence of death. These results highlight the clinical significance of arrhythmia burden during exercise testing.