Pre-existing Cardiovascular Comorbidities Research Articles

COVID-19 Pandemic and Cardiovascular Disease

There seems to be a unique interplay between 2019 novel coronavirus (SARS-CoV-2) and cardiovascular diseases, although it is predominantly a respiratory illness. Patients with pre-existing cardiovascular co-morbidities appear to be at highest risk for mortality from coronavirus disease 2019 (COVID-19) along with the elderly; COVID-19 also contributes to cardiovascular complications, including acute coronary syndromes, arrhythmias, myocarditis, acute heart failure, and, in the most severe cases, cardiogenic shock and death. Several medications proposed in the treatment of COVID-19 require cardiac monitoring owing to their cardiac-specific adverse effects. Ultimately, the COVID-19 pandemic has jeopardized the safety of heart transplantation and has placed transplant recipients on immunosuppressive therapies at significant risk. In this article, the authors summarize the rapidly emerging data on the cardiovascular implications of SARS-CoV-2 and COVID-19.

52: Major adverse cardiovascular and cerebrovascular events associated with female pelvic reconstructive surgery

To evaluate national trends in major adverse cardiovascular and cerebrovascular events (MACCE) in women undergoing pelvic reconstructive surgery (PRS). Data from the Healthcare Cost and Utilization Project National Inpatient Sample was used to identify women undergoing PRS between 2012 to 2016. Patient- and hospital-level demographic, procedural, and comorbidity data were collected. Patients were stratified into those with and those without MACCE. MACCE was defined as all-cause mortality (ACM), cardiac arrest (CA), acute myocardial infarction (AMI) and acute ischemic stroke (AIS). Descriptive statistics are expressed as medians and interquartile ranges (IQR). Pairwise analysis was performed between groups using Wilcoxon rank-sum or Fisher’s exact test as appropriate. Multivariable logistic regression was used to identify independent risk factors for MACCE. During the study period 53,540 patients underwent PRS. The rate of MACCE was 4.8 per 1,000 surgeries. The most common form of MACCE was AMI (3.7 per 1,000), followed by AIS (0.6 per 1,000), CA (0.4 per 1,000), and ACM (0.3 per 1,000). Patients experiencing MACCE were older (median 69 years, IQR: 58-76 vs 58, 46-68, p<0.001), more likely to have a household income in the 1st quartile (28.5% vs 22.9%, p=0.03), and more likely to have Medicare as their primary insurer (60.9% vs 33.6%, p<0.001). Patients experiencing MACCE were a more likely to have major pre-existing cardiovascular comorbidities, coagulopathy, neurologic disease (ND), and diabetes (Table 1). Additionally, patients experiencing MACCE were more likely to undergo robotic colpopexy (20.7% vs 9.6%, p<0.001), vaginal colpopexy (32.0% vs 28.5%, p=0.04), bilateral salpingo-oophorectomy (25.8% vs 19.6%, p=0.03) and to receive a blood transfusion (8.2% vs 2.5%, p<0.001); and less likely to undergo hysterectomy (39.5% vs 48.8%, p=0.01) and bilateral salpingectomy (3.5% vs 6.8%, p=0.03). On logistic regression, pre-existing coagulopathy was the strongest predictor of MACCE, (aOR=5.53, 95% CI: 2.39-12.78), followed by blood transfusion (aOR=4.84, 95% CI: 1.89-12.45), congestive heart failure (CHF) (aOR=3.61, 95% CI: 1.56-8.37), ND (aOR=3.14, 95% CI: 1.23-8.06), and electrolyte abnormalities (aOR=1.99, 95% CI: 1.05-3.99). MACCE after PRS is a rare event with AMI being the most common manifestation. Pre-existing ND, CHF, coagulopathy, electrolyte disturbances, and perioperative transfusions are strongly associated with MACCE.

589P - Fluoropyrimidine-induced cardiotoxicity in colorectal cancer patients: Preliminary data from the prospective observational CHECKPOINT trial (NCT02665312)

BackgroundFluoropyrimidines (FP) are the backbone chemotherapy (CT) for colorectal cancer (CRC). Although the most common toxicities have been extensively studied, FP-induced cardiotoxicity (FIC), an infrequent but potentially life-threatening toxicity, still lacks of a comprehensive characterization. The correlation between FIC and known cardiovascular (CV) risk factors remains controversial and based on retrospective observations. MethodsCRC patients (pts) treated for the first time with FP at Candiolo Cancer Institute have been enrolled since January 2016. All pts were screened for potential CV risk factors; if needed, the treatment of preexisting CV comorbidities was optimized before starting CT. During the first 3 CT cycles, a monitoring with CV symptoms collection, seriated electrocardiograms and brain natriuretic peptide (BNP) measurements was performed. Primary objective was to assess the incidence of FIC. Secondary objectives included the analysis of the relationship of FIC with known CV risk factors and BNP levels. ResultsAn interim analysis was conducted on 101 pts (65% male, median age 71.6 years). We found high prevalence of CV risk factors (BMI ≥25 54.2%, smoker 50%, heavy drinker 23%, sedentary lifestyle 63.3%) and comorbidities (diabetes mellitus 19.2%, dyslipidemia 34.7%, arterial hypertension 54%, stroke 3%, coronary artery disease 6%, arrhythmias 8%, heart failure 4%). 19 pts (18.8%) experienced FIC: 1 acute coronary syndrome (ACS), 1 coronary vasospasm, 1 paroxysmal supraventricular tachycardia (PSVT), 1 complete left bundle branch block (LBBB), 2 syncope, 4 typical chest pain, 6 sudden dyspnea, 3 sudden palpitations. After treatment of the CV events, only 3 pts had to discontinue FP (ACS, LBBB and PSTV). Among symptomatic pts, only 47% had CV comorbidities and/or CV risk factors. BNP levels increased on average by 73% [CI 99%: +39% - +106%] after the first cycle. ConclusionsA high incidence of CV events, with no apparent correlation with CV comorbidities or risk factors, was observed. Prompt identification and treatment of CV events allowed most pts to complete the treatment with FP. Clinical trial identificationNCT02665312. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureM. Aglietta: Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Merck; Advisory / Consultancy: Roche. All other authors have declared no conflicts of interest.

Mortality and Hospitalization Risk Following Oral Androgen Signaling Inhibitors Among Men with Advanced Prostate Cancer by Pre-existing Cardiovascular Comorbidities

BackgroundElderly patients (≥65yr) with advanced prostate cancer and cardiovascular disease (CVD) conditions are often excluded from clinical trials of abiraterone acetate (AA) or enzalutamide (ENZ). Consequently, little is known about the effects of these medications on these vulnerable patients. ObjectiveTo assess the short-term outcomes of AA and ENZ in patients with pre-existing CVDs. Design, setting, and participantsA population-based retrospective study. The Surveillance, Epidemiology, and End Results-Medicare–linked database was used to identify prostate cancer patients using AA or ENZ. Outcome measurements and statistical analysisThe primary endpoint was 6-mo all-cause mortality, analyzed using modified Poisson regression modeling of relative risk (RR) adjusted for confounders and comorbidities. Results and limitationsAmong eligible patients (2845 with AA and 1031 with ENZ), 67% had at least one pre-existing CVD. Compared with those without pre-existing CVDs, having one to two pre-existing CVDs was associated with 16% higher 6-mo mortality (RR=1.16, 95% confidence interval [CI]: 1.00–1.36), and the risk increased further among those having three or more CVDs (RR=1.56, 95% CI: 1.29–1.88). Most of the differences in survival of patients with pre-existing CVD condition occurred within the first 6mo of treatment. ConclusionsAfter treatment with AA or ENZ, elderly prostate cancer patients with pre-existing CVDs experienced higher short-term mortality than otherwise similar patients without CVDs. Mortality associated with CVDs did not depend on having received AA versus ENZ. Patient summaryPatients with pre-existing cardiovascular diseases (CVDs) experienced higher short-term mortality after abiraterone acetate or enzalutamide than those without pre-existing CVDs. It is recommended that a multidisciplinary team, including a cardiologist, evaluate patients having pre-existing CVDs in the process of making treatment decisions and monitoring potential side effects.

PF386 HYPERTENSION IN PATIENTS TREATED WITH IBRUTINIB FOR CHRONIC LYMPHOCYTIC LEUKEMIA (CLL)

Background:Hypertension (HTN) is the most common grade ≥ 3 Ibrutinib (Ibr)‐associated adverse event (AE) observed in clinical trials (26%) (O’Brien, Blood 2015). Meta‐analysis of clinical trial data suggests a 2.8‐fold increased risk of HTN for patients (pts) treated with Ibr vs. placebo (Caldeira, PLOS ONE 2019). In clinical practice, data regarding incidence, medication management, and long term vascular consequences of Ibr‐associated HTN are limited. As Ibr is administered in a continuous fashion and HTN incidence is cumulative, this toxicity is presently understudied.Aims:To describe the incidence of HTN, as well as baseline comorbidities, change in blood pressure (BP) over time, and changes in cardiovascular (CV) medications for CLL pts treated with Ibr in routine clinical practice.Methods:Multicenter, retrospective cohort study of CLL pts treated with 420 mg Ibr for at least 6 months. We collected baseline CV comorbidities, baseline CV medications, BP measurements prior to Ibr initiation and sequentially following exposure at specific time points over a 12‐month period, and adjustments to CV medications in response to Ibr‐associated HTN (up or 1 year). Incident HTN is defined as BP &gt; 140/90 mmHg, and worsening BP control is defined as sustained rise in SBP or DBP ≥ 3 mmHg over baseline.Results:We identified 247 Ibr treated CLL pts. Pre‐Ibr CV comorbidities included: HTN (43%), hyperlipidemia (35%), diabetes (16%), coronary artery disease (CAD; 9.7%), heart failure (2.0%), valvular heart disease (2.8%), atrial fibrillation (Afib; 4.5%), other arrhythmia (6.5%), stroke (2.8%), and smoking history (42%). At least one anti‐HTN medication was used in 51% prior to Ibr initiation (median number of meds 1, range 0–6, 33% ≥ 2 meds). Median BP prior to Ibr exposure was 127/71 mmHg (range 92–174/48–95) and median pulse 75 bpm (range 27–110). Median peak BP following Ibr exposure was significantly elevated (153/80 mmHg range 105–218/53–121, p &lt; 0.0001). Median time to peak BP was 6 months (range 0–35 months). Figure 1 depicts median systolic BP at baseline and 1, 3, 6, 9, and 12 months following Ibr initiation. During the observation period, 36% and 84% experienced new HTN or worsening of existing HTN respectively. 19.8% of pts required initiation of at least one new anti‐HTN medication, and 4.7% required increased dose of a pre‐Ibr anti‐HTN medication. Of the 49 pts who required BP management, 86% started 1 new agent, and 14% started ≥2 new agents. The most common new classes of agents selected were beta blockers (32%), angiotensin receptor blockers (21%), diuretics (19%), calcium channel blockers (14%), and angiotensin converting enzyme inhibitors (14%). Regarding CV events following Ibr initiation, 6.4% experienced new onset Afib, 1.6% had CAD. Preexisting CV comorbidities, smoking history, and diabetes were not predictive of HTN development in univariate analysis.Summary/Conclusion:HTN is a pervasive AE of Ibr affecting pts with and without baseline HTN or CV conditions. Physiologically, systolic blood pressure appears to be more significantly affected than diastolic blood pressure. While these data demonstrate 20% of pts adjust current anti‐HTN meds or start new ones, it is not known how effective current management is at controlling this AE or preventing long term vascular events. In addition, we demonstrate that the proportion of pts initiating new anti‐HTN meds appears to be significantly lower than those experiencing new/worsening HTN, identifying a potential opportunity for care optimization in partnership with cardio‐oncology.image

Anaphylaxis in Elderly Patients-Data From the European Anaphylaxis Registry.

Background: Elicitors and symptoms of anaphylaxis are age dependent. However, little is known about typical features of anaphylaxis in patients aged 65 years or more.Methods: The data from the Network for Online Registration of Anaphylaxis (NORA) considering patients aged ≥65 (elderly) in comparison to data from adults (18–64 years) regarding elicitors, symptoms, comorbidities, and treatment measures were analyzed.Results: We identified 1,123 elderly anaphylactic patients. Insect venoms were the most frequent elicitor in this group (p < 0.001), followed by drugs like analgesics and antibiotics. Food allergens elicited less frequently anaphylaxis (p < 0.001). Skin symptoms occurred less frequently in elderly patients (77%, p < 0.001). The clinical symptoms were more severe in the elderly (51% experiencing grade III/IV reactions), in particular when skin symptoms (p < 0.001) were absent. Most strikingly, a loss of consciousness (33%, p < 0.001) and preexisting cardiovascular comorbidity (59%, p < 0.001) were more prevalent in the elderly. Finally, adrenaline was used in 30% of the elderly (vs. 26% in the comparator group, p < 0.001) and hospitalization was more often required (60 vs. 50%, p < 0.001).Discussion and Conclusion: Anaphylaxis in the elderly is often caused by insect venoms and drugs. These patients suffer more often from cardiovascular symptoms, receive more frequently adrenaline and require more often hospitalization. The data indicate that anaphylaxis in the elderly tends to be more frequently life threatening and patients require intensified medical intervention. The data support the need to recognize anaphylaxis in this patient group, which is prone to be at a higher risk for a fatal outcome.

Cardiovascular Hospitalization in Patients Treated with Dasatinib or Nilotinib in Simplicity, an Observational Study of Chronic-Phase Chronic Myeloid Leukemia (CP-CML) Patients in Routine Clinical Practice

Introduction: The combined effect of cardiovascular (CV) risk and tyrosine kinase inhibitor (TKI) therapy may contribute to the incidence of CV events in patients (pts) with chronic phase chronic myeloid leukemia (CP-CML). CV events can affect the overall clinical outcomes and survival of CML patients, and hospitalization due to CV events is costly; analyzing the rates and risks of CV hospitalization in pts with CML receiving TKI therapy may help to inform treatment decisions and risk mitigation strategies and to minimize costs. SIMPLICITY (NCT01244750) is an ongoing observational study of CP-CML pts in routine clinical practice receiving first-line (1L) TKIs since 2010 in the US and Europe, exploring TKI use and management patterns in clinical practice. This analysis aims to evaluate rates of CV-related hospitalization and estimate related costs in pts treated with the second-generation TKIs dasatinib (DAS) and nilotinib (NIL).Methods: CV hospitalizations were identified retrospectively from events reported by SIMPLICITY investigators over the course of treatment with DAS or NIL, from the start of treatment (any line of therapy) to 30 days after the end of that line of therapy, or prior to the start of a subsequent line of TKI therapy, whichever was sooner. Pts were followed for a maximum of five years. Owing to the observational nature of SIMPLICITY, patients were not matched between cohorts and adjustments for covariates were not made. Kaplan-Meier methods with the log-rank test were used to estimate time to first CV hospitalization. Statistical comparisons were made using t-tests and the Mann-Whitney U test for continuous variables and chi square for categorical variables.Results: Overall, 825 pts received DAS (n=417) or NIL (n=408) as 1L therapy; 376 pts received DAS (n=214) or NIL (n=162) as second-line (2L) therapy; and 124 pts received DAS (n=63) or NIL (n=61) as third-line (3L) therapy. See table for patient baseline demographics and comorbidities. No significant differences were noted between the DAS and NIL cohorts. Median age was similar between the DAS and NIL groups at 56.2 and 54.1 years. At baseline, both groups had similar CV comorbidities. A significantly greater number of pts were treated in the US vs Europe (p=0.017).Investigators reported that, during 1L DAS and NIL therapy, 43% (n=357) of pts experienced a CV disorder: 45.3% (n=189) of DAS pts and 41.2% (n=168) of NIL pts (DAS vs NIL, p=0.28). Numbers of CV-related hospitalizations occurring during DAS and NIL therapy were 16 and 36, respectively, translating to 12.6 and 27.4 CV-related hospitalizations per 1000 pt years. Across 1L, 2L, and 3L (referred to here as ‘all lines‘) of DAS and NIL therapy, 31 and 51 CV-related hospitalizations occurred, translating to 16.7 and 28.8 CV-related hospitalizations per 1000 pt years, respectively. The three most common CV-related reasons for hospitalization were congestive cardiac failure, atrial fibrillation and myocardial infarction. The figure shows Kaplan-Meier curves of time to first CV-related hospitalization for 1L therapy, for five years of follow-up. CV-related hospitalization at 5 years of follow-up was 5% for pts on 1L DAS, 7.5% for pts on 1L NIL, 5.7% for all lines of DAS and 8.5% for all lines of NIL. Durations of hospital stay related to CV disorders for pts on 1L DAS and 1L NIL were 68 days and 263 days, translating to 53.3 and 199.8 days in hospital per 1000 pt years. Durations of hospital stay related to CV disorders for pts on all lines of DAS and NIL were 107.4 days and 226.1 days, translating to 53.3 and 199.8 days in hospital per 1000 pt years. Incremental cost differences based on mean estimates will be presented.Conclusions: CV disorders and related hospitalizations were frequently seen in patients with CP-CML in SIMPLICITY. In these patients, NIL was associated with a rate of CV hospitalization up to double that associated with DAS and lengthier hospital stay. Owing to the survival benefits conferred by TKIs, it is critical to minimize and manage complications that may arise in treated pts; potential for greater morbidity and healthcare cost should be considered when making decisions about TKIs to use in individual pts, particularly those with preexisting CV comorbidities. [Display omitted] DisclosuresMauro:Pfizer: Consultancy; Bristol-Myers Squibb: Consultancy; Takeda: Consultancy; Novartis: Consultancy, Research Funding. Chen:Bristol-Myers Squibb: Employment. Cortes:Novartis: Consultancy, Research Funding; Arog: Research Funding; Astellas Pharma: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Daiichi Sankyo: Consultancy, Research Funding. Gambacorti-Passerini:Pfizer: Consultancy, Honoraria, Research Funding; BMS: Consultancy. Sen:ICON PLC: Employment. Gajavelli:Bristol-Myers Squibb: Employment. Davis:Bristol-Myers Squibb: Employment. Michallet:Octapharma: Membership on an entity's Board of Directors or advisory committees; Chugai: Consultancy; Novartis: Research Funding.

Clinical Outcome After Mechanical Thrombectomy in Patients with Diabetes with Major Ischemic Stroke of the Anterior Circulation

Among patients with acute ischemic stroke treated with mechanical thrombectomy (MT), patients with diabetes (DP) show a poorer outcome compared with patients without diabetes (NDP). This study aims to provide a comprehensive analysis of factors associated with unfavorable outcome in DP receiving MT for stroke of the anterior circulation. This study included 317 of 498 consecutive patients who received interventional treatment for acute ischemic stroke in the terminal internal carotid artery and/or middle cerebral artery, including 46 DP. The study data included pre- and posttreatment stroke computed tomography, including perfusion data, collateral status, treatment data including treatment times, pre-existing cardiovascular risk factors, cerebrovascular events, comorbidities, laboratory parameters, and medication. Neurologic status was assessed at baseline (National Institute of Health Stroke Scale [NIHSS]/modified Rankin Scale [mRS]) and after 90 days (mRS 90). Compared with NDP, DP showed a significantly poorer outcome (mRS90 >2) (P < 0.05). Collateralization and infarct core size did not differ between groups, whereas the penumbra was significantly smaller in DP than in NDP (P < 0.05). The poorer mRS90 outcome (mRS90 > 2) in DP was associated with poor collaterals (P= 0.01) and hyperglycemia on admission (P < 0.05). Shorter time to reperfusion was associated with favorable mRS90 in the NDP (P < 0.001) but not the DP (P= 0.49) group. In univariate logistic regression, the following parameters were significantly associated with mRS90: diabetes, hyperglycemia at admission, time to reperfusion, and the NIHSS score (P < 0.05 each). In multivariate analyses and partition regression models of all variables, DP with admission hyperglycemia (≥132 mg/dL) and older age (≥66 years) showed a particularly poor outcome. The main factors for an unfavorable outcome of DP after MT are admission hyperglycemia, age, and NIHSS score.

Safety Limits of Antidepressant Use Plus Combinations: Focus on Cardiovascular Function.

Antidepressants have been widely prescribed for depression, anxiety, sleep disorders, and in the management of behavioural symptoms of adult-old patients. Although generally safe, newer generation antidepressants are not devoid of the risk of inducing clinically relevant adverse events. To investigate the association between newer generation antidepressants and the occurrence of cardiovascular adverse events and electrocardiogram (ECG) abnormalities. Studies were included in the review according to the following criteria: a) clinical trials (placebo-controlled or not) or case reports; b) short- or long-term interventions with antidepressants; c) prescription of newer generation antidepressants as first-line treatment; d) samples of adult or adult-old patients. From a total of 301 articles addressing the association between antidepressants and cardiovascular adverse events as primary or secondary outcomes, we selected 30 controlled clinical trials and 10 case reports. In most clinical studies, the effects of antidepressants on cardiac function are usually computed as secondary outcome variables, however with limited information. Conversely, case reports tend to present more comprehensive sets of clinical and laboratorial parameters, but the generalization of such data is limited by the small number of observations. The occurrence of QTc prolongation (with increased risk of torsade de pointes) has been reported. Aging, higher dosages of antidepressants, drug interaction, and pre-existing cardiovascular comorbidities were found as risk factors for the aforementioned cardiovascular and ECG abnormalities. Prescribing antidepressants requires caution given their potential impact on cardiac function, and the clinician should carefully monitor cardiovascular and ECG parameters particularly in cases with underlying heart disease.

Is topical epinephrine safe for hemostasis in endoscopic sinus surgery?

Is topical epinephrine safe for hemostasis in endoscopic sinus surgery?

Are patients in heart failure trials representative of primary care populations? A systematic review.

BackgroundGuidelines recommend drug treatment for patients with heart failure with a reduced ejection fraction (HFrEF), however the evidence for benefit in patients with mild disease, such as most in primary care, is uncertain. Importantly, drugs commonly used in heart failure account for one in seven of emergency admissions for adverse drug reactions.AimTo determine to what extent patients included in studies of heart failure treatment with beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, and aldosterone antagonists were representative of a typical primary care population with HFrEF in England.Design & settingSystematic review of randomised controlled trials (RCTs) of drug treatment in patients with HFrEF.MethodMEDLINE, MEDLINE In-Process, EMBASE, and CENTRAL were searched from inception to March 2015. The characteristics of the patient’s New York Heart Association (NYHA) classification were compared with a primary care reference population with HFrEF.ResultsOf the 30 studies included, two had incomplete data. None had a close match (defined as ≤10% deviation from reference study) for NYHA class I disease; 5/28 were a close match for NYHA class II; 5/28 for NYHA class III; and 18/28 for NYHA class IV. In general, pre-existing cardiovascular conditions, risk factors, and comorbidities were representative of the reference population.ConclusionPatients recruited to studies typically had more severe heart failure than the reference primary care population. When evidence from sicker patients is generalised to less sick people, there is increased uncertainty about benefit and also a risk of harm from overtreatment. More evidence is needed on the effectiveness of treatment of heart failure in asymptomatic patients with NYHA class I.

Desphospho-Uncarboxylated Matrix-Gla Protein Is Increased Postoperatively in Cardiovascular Risk Patients.

Background: Matrix Gla protein (MGP) is an extrahepatic protein that is dependent on glutamate carboxylation, a vitamin K-dependent process. Its dysfunctional form, desphospho-uncarboxylated-MGP, has been associated with increased arterial calcification and stiffness. The aim of this study was to measure the degree of postoperative carboxylation of MGP and two other Gla proteins in patients scheduled for abdominal or orthopaedic surgery. Methods: Forty patients undergoing abdominal or orthopaedic surgery were included. Blood samples were collected preoperatively and four days after the surgery. Desphospho-carboxylated MGP (dp-cMGP), desphospho-uncarboxylated MGP (dp-ucMGP), carboxylated osteocalcin (OC) (cOC), uncarboxylated OC (ucOC), and uncarboxylated prothrombin (PIVKA-II) were analysed. Results: Preoperatively, 29 patients had dp-ucMGP levels above the reference values. Patients with pre-existing cardiovascular comorbidities had higher dp-ucMGP preoperatively compared with patients with no record of cardiovascular disease. Postoperatively, this number increased to 36 patients, and median dp-ucMGP levels increased (p < 0.0001) and correlated to a PIVKA-II increase (r = 0.44). On the other hand, dp-cMGP levels did not significantly alter. Decreased levels of ucOC and cOC were seen after surgery (p = 0.017 and p = 0.0033, respectively). Comorbidities, possible nutritional defects, and complications affecting Gla protein activity and function were identified. Conclusions. Dp-ucMGP was high preoperatively, and had further increased postoperatively. This pattern was linked to several comorbidities, possible nutritional defects, and postoperative complications, which motivates further research about potential interactions between perioperative corrective treatments with vitamin K supplements, cardiovascular biomarkers, and incidents of stroke and myocardial infarction events.

Relationship of Preexisting Cardiovascular Comorbidities to Newly Diagnosed Atrial Fibrillation After Ischemic Stroke

There remains uncertainty as whether newly diagnosed atrial fibrillation (AF) after ischemic stroke reflects underlying heart disease and represents an increased risk of cardioembolic stroke, or whether it is triggered by neurogenic mechanisms. We aimed to determine whether cardiovascular comorbidities in patients with new AF after ischemic stroke differ from patients with previous known AF or without AF. This French longitudinal cohort study was based on the database covering hospital care from 2009 to 2012 for the entire population. Of 336 291 patients with ischemic stroke, 240 459 (71.5%) had no AF and 95 832 (28.5%) had previously known AF at baseline. Patients without previous AF had a mean CHA2DS2-VASc score of 4.98±1.63 SD. During a mean follow-up of 7.9±11.5 months, 14 095 (5.9%) of these patients had incident AF, representing an annual incidence of AF after ischemic stroke of 8.9 per 100 person-years (95% confidence interval, 8.8-9.0). New AF patients had higher CHA2DS2-VASc score, more likely comorbidities, and more frequent history of previous transient ischemic attack than patients with previous known AF or without AF. Preexisting cardiovascular comorbidities underlie AF newly diagnosed after stroke. Consequently, these high-risk patients should be closely monitored for incident AF to facilitate an earlier diagnosis of AF and avoid stroke with appropriate thromboprophylaxis.

Italian survey on benign paroxysmal positional vertigo.

SUMMARYBenign paroxysmal positional vertigo (BPPV) is the most common type of peripheral vertigo. BPPV often relapses after the first episode, with a recurrence rate between 15% and 50%. To date both the aetiopathogenetic processes that lead to otoconia detachment and the factors that make BPPV a relapsing disease are still unclear, but recent epidemiological studies have shown a possible association with cardiovascular risk factors. The aim of the present study (Sesto Senso Survey) was to evaluate in the Italian population through an observational survey, the main demographic and clinical characteristics of patients with BPPV (first episode or recurrent) with particular focus on the potential cardiovascular risk factors. The survey was conducted in 158 vestibology centres across Italy on 2,682 patients (mean age 59.3 ± 15.0 years; 39.1% males and 60.9% females) suffering from BPPV, from January 2013 to December 2014. The results showed a high prevalence of cardiovascular risk factors such as high blood pressure (55.8%), hypercholesterolaemia (38.6%) and diabetes (17.7%), as well as a family history of cardiovascular disease (49.4%). A high percentage of patients also had hearing loss (42.9%), tinnitus (41.2%), or both (26.8%). The presence of hypertension, dyslipidaemia and pre-existing cardiovascular comorbidities were significantly related to recurrent BPPV episodes (OR range between 1.84 and 2.31). In addition, the association with diabetes and thyroid/autoimmune disease (OR range between 1.73 and 1.89) was relevant. The survey results confirm the significant association between cardiovascular comorbidities and recurrent BPPV and identify them as a potential important risk factor for recurrence of BPPV in the Italian population, paving the way for the evaluation of new therapeutic strategies in the treatment of this disease.

Cardiovascular disease and resuscitated septic shock lead to the downregulation of the H2S-producing enzyme cystathionine-\u03b3-lyase in the porcine coronary artery

BackgroundDownregulation of the hydrogen sulfide (H2S)-producing enzymes cystathionine-γ-lyase (CSE), cystathionine-β-synthase (CBS), and/or 3-mercaptopyruvate sulfurtransferase (3-MST) is associated with chronic cardiovascular pathologies. Nevertheless, equivocal data are available on both the expression and function of these enzymes in coronary arteries (CA). We recently reported that atherosclerotic pigs subjected to sepsis developed impaired cardiac function, which coincided with decreased myocardial CSE expression and increased nitrotyrosine formation. To define the endogenous source(s) of H2S in the CA, we studied the expression of CBS, CSE, or 3-MST in the CA of pigs subjected to septic shock with/without pre-existing cardiovascular co-morbidity.MethodsAnesthetized and instrumented FBM "familial hypercholesterolemia Bretoncelles Meishan" pigs with high-fat diet-induced hypercholesterolemia and atherosclerosis were subjected to polymicrobial septic shock, or sham procedure, and subsequent intensive care therapy for 24 h. Young German domestic pigs were used as naïve controls. CSE, CBS, 3-MST, HO-1, eNOS, and nitrotyrosine expression was quantified by immunohistochemistry of formalin-fixed paraffin sections.ResultsFBM pigs, in the absence of septic shock, showed decreased CSE expression in the media. This decrease became more pronounced after sepsis. The expression pattern of HO-1 resembled the pattern of CSE expression. CBS protein was not detected in the media of any of the CA examined but was localized to the adventitia and only in the atheromatous plaques containing foam cells of the CA, in regions that also displayed abundant nitrotyrosine formation. The CBS expression in the adventitia was not associated with nitrotyrosine formation. 3-MST expression was not found in any of the CA samples.ConclusionsWe hypothesize that (i) the reduced CSE expression in FBM pigs may contribute to their cardiovascular disease phenotype and moreover (ii) the further decrease in CA CSE expression in sepsis may contribute to the sepsis-associated cardiac dysfunction.

Androgen deprivation therapy and cardiovascular complications.

Cardiovascular complications associated with the use of antiandrogens have already been known for some time. Based on the results of the latest meta-analyses and clinical studies published in the last few years, the attention of the scientific community is focused on the deleterious cardiovascular effects of gonadotropine-releasing hormon agonists in context of the androgen deprivating therapy. The cardiac toxicity is a problem especially in patients with preexisting cardiovascular comorbidities. Increased arterial wall thickening along with endothelial dysfunction has been observed in patients with descreased androgens levels in the peripheral blood. The treatment with gonadotropine-releasing hormon agonists may disrupt the intracellular concentration of calcium ions and the contractile process and potentially result in pathological remodelling of heart. Here, we give several possible mechanisms of action of gonadotropine-releasing hormon agonists on the cardiovascular system that may be a potential explanation of the clinical observations (Ref. 44).

Long-term general and cardiovascular safety of tiotropium/olodaterol in patients with moderate to very severe chronic obstructive pulmonary disease

BackgroundLong-term safety, particularly cardiovascular safety, is of special interest in maintenance treatment of chronic obstructive pulmonary disease (COPD) with long-acting β2-agonists and long-acting muscarinic antagonists, given potential cardiovascular effects. MethodsTwo 52-week Phase III trials (TONADO®) investigated tiotropium/olodaterol (5/5 and 2.5/5 μg) versus tiotropium 2.5, 5 μg and olodaterol 5 μg. In a pre-specified safety analysis, investigator-reported treatment-emergent adverse events (AEs), electrocardiogram and laboratory data were pooled. All serious AE (SAE) reports were reviewed by an independent Adjudication Committee, which assessed whether deaths, hospitalisations or intubations were respiratory, cardiovascular, cerebrovascular or other disease related. Subgroup analyses investigated cardiovascular safety including major cardiac events in patients with cardiovascular co-morbidities. ResultsThis analysis comprised 3100 patients with moderate to very severe COPD, treated for ≤1 year, including 784 patients with cardiovascular co-morbidities. AEs were balanced across treatments in the total population as well as in patient subgroups with pre-existing cardiovascular co-morbidities. The incidence and nature of events were consistent with the disease under study and a 1-year trial duration. 494/3100 patients contributed to an adjudicated analysis of SAEs: 260 had respiratory-related, 53 had cardiovascular-related and 16 had cerebrovascular-related SAEs. Incidences of these SAEs were comparable between treatments. There was no evidence of any increased risk for the combination compared to the monotherapy groups. ConclusionsThese data provide confidence for clinicians that tiotropium/olodaterol 5/5 μg can be safely administered once-daily to patients with moderate to very severe COPD long-term, including those with significant cardiovascular co-morbidity. Trial registryClinicalTrials.gov, Nos.: NCT01431274, NCT01431287.

Determining the Incidence and Factors of Cardiotoxicity in Breast Cancer Patients Treated With Anthracycline and/or Trastuzumab-Containing Regimen at Aurora Health Care

Background: Anthracycline and trastuzumab are common breast cancer treatments. While improving survival, they elevate risk of congestive heart failure. The incidence of cardiotoxicity (CTx) with these therapies varies in the literature from 10% to 59%, higher than those reported in clinical trials (4%–10%) that excluded patients with preexisting cardiovascular comorbidities. Studies have failed to establish consensus on the risk factors for CTx associated with these therapies.

Initiation of dialysis: Trigger or cause of cardiovascular events?

Initiation of dialysis is associated with increased morbidity and mortality. However, a question could be asked whether these events are caused by initiation of dialysis or whether dialysis serves as a trigger unveiling or worsening underlying preexisting cardiovascular comorbidities that could be pre-treated.

Cardiac complications in childhood cancer survivors treated with anthracyclines.

Cardiovascular complications are among the leading causes of morbidity and mortality among survivors of childhood cancer, after cancer relapse and secondary malignancies. Although advances in cancer treatment have improved the 5-year survival rates, the same treatments, such as anthracyclines, that cure cancer also increase the risk for adverse cardiovascular effects. Anthracycline-related cardiotoxicity in survivors of childhood cancer is progressive and can take years to develop, initially presenting as sub-clinical cardiac abnormalities that, if left undetected or untreated, can lead to heart failure, myocardial infarction, or other clinical cardiac dysfunction. A higher cumulative dose of anthracycline is associated with cardiotoxicity in children; however, sub-clinical cardiac abnormalities are evident at lower doses with longer follow-up, suggesting that there is no "safe" dose of anthracycline. Other risk factors include female sex, younger age at diagnosis, black race, trisomy 21, longer time since treatment, and the presence of pre-existing cardiovascular disease and co-morbidities. Cardioprotective strategies during treatment are limited in children. Enalapril provides only temporary cardioprotection, whereas continuous anthracycline infusion extends none. On the other hand, dexrazoxane successfully prevents or reduces anthracycline-related cardiotoxicity in children with cancer, without increased risks for recurrence of primary or second malignancies or reductions in anti-tumour efficacy. With more childhood cancer survivors now reaching adulthood, it is vital to understand the adverse effects of cancer treatment on the cardiovascular system and their long-term consequences to identify and establish optimal prevention and management strategies that balance oncologic efficacy with long-term safety.