Prior Cardiovascular History Research Articles

A Race Against Time: Coronary Computed Tomography Angiography Discovers a Highly Inflamed Plaque in 49-Year-Old Right Before STEMI

Abstract In the modern management of coronary artery disease (CAD), cardiac computed tomography angiography (CCTA) has emerged as a pivotal diagnostic tool, offering detailed visualization of coronary artery lumens and atherosclerotic plaques. We present the case of a 49-year-old woman, with no prior cardiovascular history but with several risk factors, in whom CCTA identified a highly inflamed atherosclerotic plaque, which led immediately to an acute myocardial infarction. Significantly, this case spotlights the vital role of perivascular inflammation mapping in CCTA, crucial for identifying high-risk plaques. The case emphasizes the necessity for a comprehensive, multifaceted diagnostic approach in the evaluation and management of CAD, incorporating advanced techniques like perivascular inflammation mapping for a more accurate and predictive assessment.

FRI244 Autoimmune Polyglandular Syndrome Type 2 And Peripartum Cardiomyopathy: A Case Report

Abstract Disclosure: A.G. Jimenez: None. J.D. Christensen: None. P. Surampudi: None. S. Phatak: None. J. Yoon: None. Background: Peripartum cardiomyopathy (PPCM) is a diagnosis of exclusion with evolving understanding of pathophysiology. There is limited consideration of the autoimmune processes contributing to PPCM. Case Presentation: A 20-year-old female had a recent delivery complicated by placenta previa, hemorrhage requiring transfusion, and pelvic infection. She presented 2 weeks postpartum with altered mental status and abdominal pain, found to be in septic shock, acute respiratory failure, acute liver injury initially thought to be secondary to retained products of conception. Subsequently, she was diagnosed with moderate-to-severe PPCM as she developed signs of heart failure, low ejection fraction <35%, mild ventricular dilatation, cardiogenic shock, hemorrhagic pericardial effusion with tamponade. She had no other prior cardiovascular history. She was briefly started on bromocriptine for treatment of suspected prolactin-mediated PPCM, in addition to digoxin, as her blood pressure was unable to sustain other treatments for PPCM. However, she hemodynamically decompensated and required persistent pressor support, leading to evaluation for other causes. Due to her prior history of hypothyroidism, an adrenal evaluation with a cosyntropin stimulation test was done. It demonstrated an undetectable cortisol at 0, 30, 60 minutes, with an elevated ACTH (1256, n=7-63 ng/dL), consistent with primary adrenal insufficiency (PAI). Workup for PAI did not reveal any infectious, infiltrative, vascular, pharmacological, or neoplastic etiology. Lab workup for concomitant hypophysitis was significant for low IGF-1 (Z-score -5.8, n= -2.0 to +2.0), but otherwise had expected elevated prolactin (121 ng/mL, n=5.2-26.5 ng/mL), suppressed LH (0.3 mIU/mL) and FSH (2.4 mIU/mL), and normal TSH (3.87 mIU/mL, n=0.27-4.20 mIU/mL) on levothyroxine 100 mcg. She had normal parathyroid hormone and hemoglobin A1c levels with no history of chronic candidiasis. Further workup showed positive antibodies to adrenal 21-hydroxylase enzyme, thyroid peroxidase, and glutamic acid decarboxylase 65, suggestive of autoimmune polyglandular syndrome (APS) type 2. She was started on glucocorticoids and mineralocorticoids for adrenal insufficiency resulting in a significant clinical improvement. She was subsequently discharged in stable condition. Conclusion: Due to increased rates of mortality in PPCM (4-11%), thought should be given to nontraditional etiologies of cardiac failure. Although rare, adrenal insufficiency must be considered in those with moderate-to-severe PPCM who continue to decompensate despite treatments. Untreated adrenal insufficiency can result in fatal consequences if not immediately treated. APS type 2 should be considered even in those without any confirmed family history of autoimmune disease. Those with autoimmune tendencies may be at higher risk of PPCM. Presentation: Friday, June 16, 2023

Time-varying testosterone level and risk of myocardial infarction and stroke among hypogonadal men: a longitudinal study in Germany

Background and objective: Findings on the association between testosterone and cardiovascular risk in men have been inconsistent. Previous studies investigated this association based on testosterone level measured at one single point in time (e.g., testosterone level at the baseline visit), which might not be relevant for the future cardiovascular events that occurred many years later, given the dynamic changes of testosterone level over time. Additionally, as compared to patients without prior cardiovascular history, those with prior cardiovascular events are more likely to have pathological changes in coronary or peripheral vasculature, and therefore more susceptible to cardiovascular events when exposed to risk factors. However, whether time-varying testosterone level affects differently between patients with prior cardiovascular events and those without is unknown. The objective of this study was to investigate the association between time-varying testosterone level and risks of myocardial infarction and stroke, and compared the associations stratified by patient’s prior cardiovascular event history. Material and methods: We used data of 376 hypogonadal men from a registry study in Germany with up to 11 years’ follow-up and applied Cox proportional hazards regression models to investigate the proposed association. Results: No association was found between baseline testosterone level and risks of myocardial infarction and stroke. When taking into account the changes of testosterone level over time and including testosterone as a time-varying covariate in the model, the adjusted hazard ratio (HR) for myocardial infarction associated with 1 nmol/L increase in testosterone level was 0.78 (95% CI: 0.64, 0.97); no association between time-varying testosterone level and stroke was found. The associations between testosterone level and cardiovascular risk were not different among patients with prior cardiovascular event history and those without. Conclusion: One baseline measurement of testosterone level may be insufficient to predict one’s future risk of cardiovascular events; regular monitoring of testosterone levels may be useful to assess the short-term cardiovascular risk in men.

533 Uncommon ECG presentation in Tako-tsubo syndrome

Abstract Aims We present the case of an 80-year-old woman without prior cardiovascular history, recent instrumental diagnosis of peritoneal carcinomatosis and ongoing oncologic diagnostic work up. Methods and results The patient was admitted to our ED for acute-onset worsening dyspnoea. On first clinical evaluation, she denied typical angina, remarkable clinical features were dyspnoea, tachycardia and hypotension. Admission ECG showed sinus rhythm with posterior and inferior ST elevation (leads DII, aVF, V5, V6) with reciprocal ST segment depression in leads V1–V2. Echocardiography confirmed infero-postero-lateral akinesia determining moderate reduction of LVEF (35–40%), normal aortic root, no pericardial effusion. Laboratory tests revealed normal WBC count, mild anaemia (HB 10.7 g/dl), normal renal function, elevated C-reactive protein (139 mg/l, n.v. < 8). Cardiac troponin I (cTnI) was normal on admission, with significant delta on second determination (0.012 > 2.5 ng/ml, nv < 0.023). ST elevation persisted after BP normalization and hypoxia treatment; so, taken into account the increased procedural risk due to patient’s age and comorbidities, however we decided to perform urgent coronary angiography. Surprisingly, coronary angiography revealed absence of any significant stenosis, with TIMI 3 flow in any coronary segment. The patient was then admitted to the ICU with diagnosis of MINOCA. The next day ECG revealed normalization of ST segment and Q wave in V2–V3. On day 2 new ECG showed new ventricular repolarization abnormalities with T wave inversion in precordial leads. Peak hs-cTnI was >15 000 ng/l. Repeat echocardiography on day 2 reported complete akinesia of all the apical segments of the LV with normo-hyperkinesia of the mid-basal segments (apical ballooning pattern) and severely depressed systolic function (FE 32–35%). During the following days patient’s symptoms improved, with rapid weaning from oxygen therapy and stable haemodynamic parameters. After 10 days the patient repeated echocardiography, which revealed improvement of global LVEF and persisting mild apical hypokinesia, suggesting the diagnostic hypothesis of Tako-Tsubo Syndrome (TTS) or TTS-phenocopy (unfortunately cardiac MRI was not performed). The patient was therefore transferred to oncology department to complete the diagnostic work-up; primary mammary neoplasia was identified, moreover associated with metastasis in the liver and the brain. Unfortunately, the patient died a month later due to non-cardiac causes. This is the case report of an uncommon MINOCA, which presented mimicking inferolateral acute STEMI, but subsequent ECG and echocardiographic evolution showed the more typical TTS pattern, with apical ballooning on echo and deep negative T waves in anterior leads. Conclusions The prevalence of MINOCA is estimated to be 6% to 8% among patients diagnosed with MI, especially women, however it is more common in patients with NSTEMI compared with STEMI; moreover in cases of TTS presenting with ST elevation, usually the elevation is found in anterior leads without reciprocal ST depression; in this patient instead ST elevation was inferolateral with reciprocal anterior ST depression. Absence of obstructive CAD and clinical/echocardiographic evolution allowed us to confirm the diagnosis of MINOCA/TTS.

Prediction of obstructive coronary artery disease after Rb-82 PET myocardial perfusion imaging and coronary artery calcium scoring using machine learning

Abstract Funding Acknowledgements Type of funding sources: None. Background Accurate risk stratification in patients with suspected stable coronary artery disease (CAD) is essential for choosing an appropriate treatment strategy but remains challenging in clinical practice. Purpose Our aim was to develop and validate a risk model to predict the presence of obstructive CAD after Rubidium-82 PET and a coronary artery calcium score (CACS) scan using a machine learning (ML) algorithm. Methods We retrospectively included 1007 patients without prior cardiovascular history and a low-intermediate pre-test likelihood, referred for rest and regadenoson-induced stress Rubidium-82 PET combined with a CACS scan. Multiple features were included in the ML model; PET derived features such as summed difference score and flow values, CACS, cardiovascular risk factors (cigarette smoking, hypertension, hypercholesterolemia, diabetes, positive family history of CAD), medication; age; gender; body mass index; creatinine serum values; and visual PET interpretation. An XGBoost ML algorithm was developed using a subset of 805 patients to predict obstructive CAD by using 5-fold cross validation in combination with a grid search. Obstructive CAD during follow-up was defined as a significant stenosis during invasive coronary angiography, a percutaneous coronary intervention or a coronary artery bypass graft procedure. The ML algorithm was validated with unseen data of the remaining 202 patients. Results Application of the XGBoost algorithm resulted in an area under the curve (AUC) of 0.93 using the training data (n = 805) and an AUC of 0.89 using the unseen data (n = 202) in predicting obstructive CAD. The strongest predictors were the CAC-scores and quantitative PET derived features. The classical risk factors and medication hardly provided an added value in the prediction of obstructive CAD. Conclusion The developed ML algorithm is able to provide individualized risk stratification by predicting the probability of obstructive CAD. Although validation with a larger dataset could result in a more well defined performance range, this model already shows potential to be implemented in the diagnostic workflow.

Feasibility and patient perception of a web-based exercise program during COVID pandemic in breast and ovarian cancer patients.

e13623 Background: Current literature shows us that therapeutic exercise has multiple benefits in oncology patients, such as improvement in quality of life or a reduction in cancer-related fatigue. Furthermore, given the risk of obesity, both exercise and diet play a key role in recovery from cancer. As a consequence of the COVID-19 pandemic, oncology patients present more difficulties to attend programs as they are considered a risk population, so new online exercise programs should be developed to ensure that patients take advantage of them in the post-COVID era. The main objective was to study patient´s perspectives and the feasibility of a web-based tailored and supervised therapeutic exercise program during COVID pandemic. Methods: A prospective study was performance on patients recruited from the Medical Oncology Unit of the Hospital Virgen de la Victoria, Malaga. Participants were between 18 and 65 years old and diagnosed of early resected breast cancer after finishing chemotherapy (CT) or metastatic ovarian (MOC) or breast cancer (MBC) with or without active treatment. Patients had had a good performance status (PS) with no prior cardiovascular history, and they were excluded if they were not used to online technologies. The duration of the program was 3 months, twice a week, delivered by a physiotherapist and a nutritionist. At the end of the program, women were asked 9 questions about their perspectives on the program. All of them signed informed consent. Results: 17 breast cancer survivor (BCS), 10 MBC and 3 MOC patients were initially recruited. From 30 patients recruited, 5 BCS did not started the program because of clinical contraindication and 5 patients left due to personal issues. 15 out of the remaining 20 completed the survey. All of patients reported that the program had contributed to improve their mood during the pandemic due to issues such functional ability, feeling better or less asthenia, and serving as improvement and encouragement in their lives. 86,7% reported having met their objectives and 100% reported going to continue doing some type of exercise or physical activity on a regular basis after the program is finished. Regarding advantages of online format compared to the face-to-face one, they reported avoiding displacement and lower risk of contagion. Lately, if they could participate again, 50% reported they would prefer online, while the remining 50% would prefer traditional modality. Conclusions: At the light of these results, the tele-exercise program contributed to improve the mood and fatigue of patients during the pandemic. The web-based program seems to be feasible and allow patients to meet their objectives after program completion and encourage them to keep doing some type of physical activity.

Post-PCI acute heart failure is an independent predictor of long-term mortality in patients with chronic kidney disease

BackgroundThis study aimed to clarify the association of post-percutaneous coronary intervention (PCI) acute heart failure (AHF) with all-cause long-term mortality in patients with chronic kidney disease (CKD). MethodsIn this prospective, observational study, 610 patients with CKD and coronary artery disease (CAD) undergoing PCI were included in the final analysis. Patients were divided to the non post-PCI AHF group (n = 557) and the post-PCI AHF group (n = 53). The diagnosis of post-PCI AHF was based on symptoms, prior cardiovascular history, and potential cardiac and noncardiac precipitants. ResultsThe overall incidence of post-PCI AHF was 53/610 (8.7%). The incidence of all-cause long-term mortality was significantly higher in the post-PCI AHF group than in the non post-PCI AHF group (50.9% vs 23.2%, P < .01). The median follow-up period was 7.3 years (interquartile range: 3.7–8.4). After adjusting for left ventricular ejection fraction <40% at discharge, CKD stage, acute myocardial infarction, age and smoking, post-PCI AHF was the strongest predictor of all-cause long-term mortality (hazard ratio: 8.08; 95% CI: 3.04–21.48; P < .01). ConclusionsIn patients with CKD and CAD undergoing PCI, post-PCI AHF is the strongest predictor of all-cause long-term mortality.

Impact of age on the effect of pre-hospital P2Y12 receptor inhibition in primary percutaneous coronary intervention for ST-segment elevation myocardial infarction: the ATLANTIC-Elderly analysis

The aim of the study was to examine the main results of the ATLANTIC trial in patients with ST-elevation myocardial infarction (STEMI), randomised to pre- versus in-hospital ticagrelor, according to age. Patients were evaluated by age class (<75 vs. ≥75 years) for demographics, prior cardiovascular history, risk factors, management, and outcomes. Elderly patients (≥75 years; 304/1,862) were more likely to be women, diabetic, lean, with a prior history of myocardial infarction and CABG, and with comorbidities (p<0.01 for all). Elderly patients presented more frequently with acute heart failure and less frequently had thromboaspiration, a stent implanted (p<0.01) and an aggressive antithrombotic regimen. Elderly patients had lower rates of pre- and post-PCI ≥70% ST-segment elevation resolution (43.9% vs. 51.6%; p=0.035), of pre- and post-PCI TIMI 3 flow (17.1% vs. 27.5%, p=0.0002), and a higher rate of the composite of death/MI/stroke/urgent revascularisation (9.9% vs. 2.9%; OR 3.67, 95% CI [2.27; 5.93], p<0.0001) and mortality (8.5% vs. 1.5%; OR 6.45, 95% CI [2.75; 15.11], p<0.0001). There was a non-significant trend towards more frequent major bleedings among elderly patients (TIMI major 2.3% vs. 1.1%; OR 2.13, 95% CI [0.88; 5.18], p=0.095). There was no significant interaction between time of ticagrelor administration (pre-hospital versus in-lab) and class of age for all outcomes. Elderly patients, who represented one sixth of the patients randomised in the ATLANTIC trial, had less successful mechanical reperfusion and a sixfold increase in mortality at 30 days, probably due to comorbidities and possible undertreatment. The effect of early ticagrelor was consistent irrespective of age.

30-Year-Old Man With Outside-of-Hospital Cardiac Arrest

30-Year-Old Man With Outside-of-Hospital Cardiac Arrest

Guidelines and Implications for Selecting Preoperative Cardiac Stress Tests

Nurse practitioners frequently manage patients who have cardiac risks and need further evaluation before their elective surgery. Cardiac stress testing can provide important needed data. Cardiac stress testing includes exercise treadmill testing; echocardiography, with exercise or pharmacologically; myocardial perfusion stress testing; and magnetic resonance angiography. Although a number of factors need to be considered, including prior cardiovascular history and type of surgical risk, a nurse practitioner’s selection of the appropriate cardiac stress test needs to include the benefit-risk ratio and the level of evidence supporting the clinical decision-making process.

Testosterone treatment is not associated with increased risk of adverse cardiovascular events: results from the Registry of Hypogonadism in Men (RHYME).

The aim of this study was to assess cardiovascular (CV) safety of testosterone replacement therapy (TRT) in a large, diverse cohort of European men with hypogonadism (HG). The Registry of Hypogonadism in Men (RHYME) was designed as a multi-national, longitudinal disease registry of men diagnosed with hypogonadism (HG) at 25 clinical sites in six European countries. Data collection included a complete medical history, physical examination, blood sampling and patient questionnaires at multiple study visits over 2-3years. Independent adjudication was performed on all mortalities and CV outcomes. Of 999 patients enrolled with clinically diagnosed HG, 750 (75%) initiated some form of TRT. Registry participants, including both treated and untreated patients, contributed 23900 person-months (99.6% of the targeted) follow-up time. A total of 55 reported CV events occurred in 41 patients. Overall, five patients died of CV-related causes (3 on TRT, 2 untreated) and none of the deaths were adjudicated as treatment-related. The overall CV incidence rate was 1522 per 100000 person-years. CV event rates for men receiving TRT were not statistically different from untreated men (P=.70). Regardless of treatment assignment, CV event rates were higher in older men and in those with increased CV risk factors or a prior history of CV events. Age and prior CV history, not TRT use, were predictors of new-onset CV events in this multi-national, prospective hypogonadism registry.

Prior chronic clopidogrel therapy is associated with increased adverse events and early stent thrombosis.

Despite the growing use of clopidogrel, limited data exist regarding the prognostic significance of chronic clopidogrel therapy in patients sustaining acute coronary syndrome (ACS). Our aim was to determine whether patients sustaining ACS while on chronic clopidogrel therapy have a worse prognosis than clopidogrel-naïve patients. A total of 5,386 consecutive ACS patients were prospectively characterised and followed-up for 30 days. Of them, 680 (13%) were treated with clopidogrel prior to the index ACS. Major adverse cardiovascular events (MACE) were defined as death, recurrent ACS, stroke and/or stent thrombosis. Compared with clopidogrel-naïve, chronic clopidogrel-treated patients were older (66 ± 12 vs 63 ± 13, respectively; p<0.01), suffered more from diabetes mellitus, hypertension, dyslipidaemia, prior cardiovascular history, including prior myocardial infarction, revascularisation, coronary artery bypass graft and stroke (p<0.01 for all), and were less likely to present with ST-elevation myocardial infarction (21% vs 45%; respectively; p < 0.001). Prior clopidogrel therapy was associated with a two-fold increase in in-hospital (1.6% vs 0.6%, respectively; p =0.006) as well as 30-day stent thrombosis (2.2% vs 1.0%, respectively; p=0.007). MACE at 30 days was also higher among chronic clopidogrel-treated compared with clopidogrel-naïve patients [12.3% vs 9.4%, respectively; p<0.01]. In multivariate log regression analysis chronic clopidogrel treatment was an independent predictor of stent thrombosis [OR=2.6 (95%CI 1.2-5.6), p=0.001]. Patients sustaining ACS while on chronic clopidogrel treatment are at higher risk for in-hospital and 30-day adverse outcomes, including stent thrombosis.

Influenza H1N1 infection leading to cardiac tamponade in a previously healthy patient: A case report

Introduction: The cardiac manifestations of influenza A are broad, ranging from self-limited pericarditis to fatal cardiomyopathy. The 2009 H1N1 influenza A (H1N1) strain is a rare cause of pericarditis, and its role in developing a pericardial effusion leading to tamponade has infrequently been reported. Case Presentation: We describe a case of a young female with no prior cardiovascular history who presents with a pericardial effusion and shock secondary to cardiac tamponade from pericarditis due to H1N1 influenza A. Conclusions: This case highlights the potential severity of H1N1 infections and the utility of considering cardiac tamponade in patients presenting with influenza symptoms and circulatory collapse.

Who Must We Target Now to Minimize Future Cardiovascular Events and Total Mortality?: Lessons From the Surveillance, Prevention and Management of Diabetes Mellitus (SUPREME-DM) Cohort Study.

Examining trends in cardiovascular events and mortality in US health systems can guide the design of targeted clinical and public health strategies to reduce cardiovascular events and mortality rates. We conducted an observational cohort study from 2005 to 2011 among 1.25 million diabetic subjects and 1.25 million nondiabetic subjects from 11 health systems that participate in the Surveillance, Prevention and Management of Diabetes Mellitus (SUPREME-DM) DataLink. Annual rates (per 1000 person-years) of myocardial infarction/acute coronary syndrome (International Classification of Diseases-Ninth Revision, 410.0–410.91, 411.1–411.8), stroke (International Classification of Diseases-Ninth Revision, 430–432.9, 433–434.9), heart failure (International Classification of Diseases-Ninth Revision, 428–428.9), and all-cause mortality were monitored by diabetes mellitus (DM) status, age, sex, race/ethnicity, and a prior cardiovascular history. We observed significant declines in cardiovascular events and mortality rates in subjects with and without DM. However, there was substantial variation by age, sex, race/ethnicity, and prior cardiovascular history. Mortality declined from 44.7 to 27.1 (P<0.0001) for those with DM and cardiovascular disease (CVD), from 11.2 to 10.9 (P=0.03) for those with DM only, and from 18.9 to 13.0 (P<0.0001) for those with CVD only. Yet, in the [almost equal to]85% of subjects with neither DM nor CVD, overall mortality (7.0 to 6.8; P=0.10) and stroke rates (1.6–1.6; P=0.77) did not decline and heart failure rates increased (0.9–1.15; P=0.0005). To sustain improvements in myocardial infarction, stroke, heart failure, and mortality, health systems that have successfully focused on care improvement in high-risk adults with DM or CVD must broaden their improvement strategies to target lower risk adults who have not yet developed DM or CVD.

Regadenoson provides perfusion results comparable to adenosine in heterogeneous patient populations: A quantitative analysis from the ADVANCE MPI trials

BackgroundTotal and reversible left ventricular (LV) perfusion defect size (PDS) predict patient outcome. Limited data exist as to whether regadenoson induces similar perfusion abnormalities as observed with adenosine. We sought to determine whether regadenoson induces a similar LV PDS as seen with adenosine across varying patient populations. Methods and ResultsADVANCE MPI were prospective, double-blind randomized trials comparing regadenoson to standard adenosine myocardial perfusion tomography (SPECT). Following an initial adenosine SPECT, patients were randomized to either regadenoson (N = 1284) or a second adenosine study (N = 660). SPECT quantification was performed blinded to randomization and image sequence. Propensity analysis was used to define comparability of regadenoson and adenosine perfusion results. Baseline clinical and SPECT results were similar in the two randomized groups. There was a close correlation between adenosine and regadenoson-induced total (r2 = 0.98, P < .001) and reversible (r2 = 0.92, P < .001) PDS. Serial differences in total (0.00 ± 3.51 vs −0.11 ± 3.46, P = .51) and reversible (0.15 ± 3.79 vs 0.07 ± 3.33, P = .65) PDS were also comparable in patients randomized to regadenoson vs adenosine, respectively, and irrespective of age, gender, diabetic status, body mass index, or prior cardiovascular history. By propensity analysis, regadenoson-induced total PDS was significantly larger than observed with adenosine. ConclusionThis is the first study to show that regadenoson induces similar, if not larger, perfusion defects than those observed with adenosine across different patient populations and demonstrates the value of quantitative analysis for defining serial changes in SPECT perfusion results. Regadenoson should provide comparable diagnostic and prognostic SPECT information to that obtained with adenosine.

Ventricular septal rupture: A rare post-myocardial infarction complication with a very high mortality rate

A 69-year-old diabetic and hypertensive man with no prior cardiovascular history was admitted to the emergency department complaining of dizziness and extreme fatigue. He had noticed worsening dyspnea for a few days without chest pain. The electrocardiogram showed deep Q waves with persistent ST-segment elevation in the anterior leads (Fig. 1a). Physical examination revealed a pansystolic murmur and systemic hypoperfusion signs including skin pallor and cold extremities and vital signs showed hypotension (85/66), sinus tachycardia (120 bpm) and low oxygen saturation (83% with ambient air). Troponine I (62 ug/L, n < 0.09 ug/L), creatine kinase (1447 U/L, n < 222 U/L) and LDH (2838 U/L, n < 240) were concordant with a sub-acute presentation. A transthoracic echocardiography (TTE) confirmed the suspicion of an extensive antero-septo-apical akinesia with an apical aneurysm and a severly impaired left ventricular ejection fraction (35%). The TTE also revealed a left-toright shunt (maximal systolic gradient of 28 mmHg) at the apex due to a 7 mm diameter ventricular septum rupture (VSR) (Fig. 1b). On the basis of these findings, we concluded to cardiogenic shock in the context of a VSR complicating a sub-acute anterior myocardial infarction (MI). An emergency coronary angiography revealed total occlusion of the mid left anterior descending coronary artery (LAD) (Fig. 1c) with no collateral flow. No revascularization was attempted since no significant benefit was

Bisphosphonates and Mortality in Women with CKD and the Presence or Absence of Cardiovascular Disease

A modest protective association between bisphosphonate prescription and mortality among women with CKD but without clinically manifest cardiovascular disease has been shown. Whether a prior cardiovascular event (myocardial infarction, stroke, or heart failure) modifies this association is unknown. A cohort of adult women with stages 3 and 4 CKD receiving primary care in a rural integrated health care system during the period 2004-2011 without history of advanced malignancy or organ transplantation (n=6756, median age=74 years, median follow-up=4.3 years) was retrospectively assembled. The primary analysis compared those patients prescribed bisphosphonates (both prevalent and incident use during follow-up) with those patients not prescribed. Additional approaches were taken to account for survival and indication biases. The primary outcome was time to death by Cox multivariable regression. In the primary analysis, compared with women not prescribed a bisphosphonate, the hazard ratio (95% confidence interval) for death among women prescribed a bisphosphonate was 0.90 (0.78 to 1.04) if there was no history of cardiovascular event but 1.22 (1.04 to 1.42) if there was history of cardiovascular event (P for interaction=0.004). In the additional approaches, associations between bisphosphonate prescription and mortality among those patients with a prior cardiovascular history varied: hazard ratios (95% confidence intervals) were 1.25 (1.01 to 1.57), 1.48 (1.16 to 1.88), and 0.94 (0.66 to 1.34). Interaction by prior cardiovascular event history varied across these three approaches (P=0.07, P=0.22, and P=0.05). In this study of women with CKD, the association between bisphosphonate treatment and mortality risk was inconclusive across a series of analyses designed to account for various types of selection and indication bias.

Increased mean platelet volume is associated with non-responsiveness to clopidogrel

Prior studies have demonstrated significant individual variability of platelet response to clopidogrel, which affects clinical outcome. In patients with stable coronary artery disease (CAD) smoking, diabetes mellitus, elevated body mass index and renal insufficiency, significantly impact response to clopidogrel. The determinants of platelet response to clopidogrel in patients with acute coronary syndrome are unknown. Adenosine diphosphate (ADP)-induced platelet aggregation (PA), hs C-reactive protein, platelet count and mean platelet volume (MPV) were determined 72 hours post clopidogrel loading in 276 consecutive acute myocardial infarction (AMI) patients. Patients with ADP-platelet aggregation ≥ 70% were considered to be clopidogrel non-responders. Eighty-four patients (30%) were clopidogrel non-responders and 192 (70%) were responders (ADP-induced PA: 81 ± 17% vs 49 ± 17%, respectively, p<0.001). Both study groups were comparable with respect to age, gender, prior cardiovascular history, prior aspirin use and risk factors for CAD, including smoking (42% for both groups) and diabetes mellitus (26% vs 22%, respectively, p=0.4). Responders and non-responders had similar angiographic characteristics, indices of infarct size, and similar hs-CRP (29 ± 34 vs 28 ± 34 mg/l, p=0.7) and creatinine (1.08 ± 0.4 mg% vs 1.07 ± 0.4, p=0.9) levels. On the contrary non-responders had significantly larger mean MPV (9 ± 1.2 fl vs 8 ± 1 fl, respectively, p=0.0018), and when patients were stratified into quartiles based on MPV, ADP-induced PA increased gradually and significantly across the quartiles of MPV (p<0.001). In conclusion, increased MPV associated with platelet activation, predicts non-responsiveness to clopidogrel among patients with acute coronary syndrome.

Potential modification of the UKPDS risk engine and evaluation of macrovascular event rates in controlled clinical trials

BackgroundThe aim of this study was to evaluate a modified UKPDS risk engine in order to establish a risk prediction benchmark for the general diabetes population.MethodsData sources were summary demographic and risk factor data from the major type 2 diabetes mellitus outcomes studies, including ACCORD, ADVANCE, VADT, RECORD, PROactive, ADOPT, and BARI 2D. Patients in these studies spanned a wide spectrum of disease, from drug-naïve to insulin-dependent. Cardiovascular events/major adverse coronary events (CVE/MACE) were primary or safety end points. Overall observed rates for cardiovascular events/MACE were summarized, and the observed annualized event rates were calculated using linear approximation. Simulation studies were then conducted using original (cardiovascular history excluded) and modified (cardiovascular history included) United Kingdom Prospective Diabetes Study (UKPDS) models; the predicted event rates were then compared with the observed event rates for all studies. The consistency of the predicted rates derived from each model was then evaluated using descriptive statistics and linear regression.ResultsThe original UKPDS model tended to overestimate event rates across studies. The ratio of predicted events versus observed MACE ranged from 0.9 to 2.0, with mean of 1.5 ± 0.4 and a coefficient of variation of 26% (R2 = 0.80). However, cardiovascular risk predictions were more precise using a modified UKPDS model; the ratio of predicted versus observed MACE events ranged from 1.8 to 2.4, with a mean of 2.1 ± 0.25 and a coefficient of variation of 13% (R2 = 0.94).ConclusionA modified UKPDS model which includes adjustments for prior cardiovascular history has the potential for use as a tool for benchmarking and may be useful for predicting cardiovascular rates in clinical studies. This modification could be further evaluated, recalibrated, and validated using patient-level information derived from prospective clinical studies to yield greater predictability.

Cardiovascular outcomes in hypertensive patients

To determine whether blood pressure (BP) control in hypertensive patients achieved with combination drug therapy provides the same cardiovascular benefits as with single-agent therapy. Drug combinations, most often including hydrochlorothiazide (HCTZ), are now recommended for routine BP management, but their effects on cardiovascular event rates have not been compared with effective monotherapy. We conducted retrospective analyses of the Valsartan Antihypertensive Long-term Use Evaluation (VALUE) data. VALUE compared cardiovascular event rates of valsartan and amlodipine. Patients with BPs not controlled (<140/90 mmHg) by the single agents had HCTZ and, if required, additional drugs of different classes, added. Using data pooled from the two treatment arms, we have now divided patients into those controlled on monotherapy and those controlled or not controlled by combination therapy. The primary study endpoint was first occurrence of cardiovascular death or nonfatal myocardial infarction or stroke. Comparisons between groups were by Cox regression, adjusted for on-treatment BP, age, prior cardiovascular events and left ventricular hypertrophy; the comparison between the monotherapy and combination therapy controlled groups was based on events occurring after 3 months by when the decision to use monotherapy or combination therapy was made. The primary endpoint occurred in 505 of 5924 (8.5%) monotherapy and 511 of 4621 (11.1%) combination therapy controlled patients: hazard ratio was 0.80 [95% confidence interval (CI) 0.70-0.90]. If these two groups were matched for baseline BPs and all events included from study baseline, the hazard ratio was 0.76 (95% CI 0.67-0.86). The difference between combination controlled and uncontrolled [434 of 3390 (12.8%)] groups was not significant [hazard ratio 0.90 (95% CI 0.80-1.03], nor when they were matched for baseline BPs [hazard ratio 0.95 (95% CI 0.81-1.11)]. Independent of prior cardiovascular history or baseline BP, hypertensive patients requiring combination therapy, which includes a thiazide diuretic for BP control, have a poorer cardiovascular prognosis than those controlled by monotherapy and only a nonsignificantly lower event rate than noncontrolled patients.