BNT162b2-vaccine-induced neutralization responses are immune correlates of clinical protection against SARS-CoV-2 in heart transplant recipients.

BACKGROUND: Defining immune correlates of protection against COVID-19 is pivotal for optimizing the use of COVID-19 vaccines, predicting the impact of novel variants on clinical outcomes, and advancing the development of immunotherapies and next-generation vaccines. We aimed to identify vaccine-induced immune correlates of protection against COVID-19-related hospitalizations in a highly vaccinated heart transplant (HT) cohort. METHODS: In a case-control study of HT recipients vaccinated with the BNT162b2 vaccine, patients were prospectively assessed for vaccine-induced neutralization of the wild-type virus, and the Delta and Omicron BA.1, BA.2, BA.4, and BA.5 variants. Comparative analyses with controls were conducted to identify correlates of protection against COVID-19 hospitalization. ROC analyses were performed. Primary outcomes were COVID-19 hospitalizations and severity of SARS-CoV-2 breakthrough infection. RESULTS: The study cohort comprised 59 HT recipients aged 58 (49,65) years with breakthrough infections after three or four monovalent BNT162b2 doses; 41 (69.5%) were men. Thirty-six (61%) patients with COVID-19 were hospitalized; most cases were non-severe (58, 98%). For hospitalized (vs. non-hospitalized) COVID-19 patients, vaccine-induced neutralization titers were significantly lower against all SARS-CoV-2 variants (p < .005). Vaccine-induced neutralization of the wild-type virus and delta and omicron BA.1, BA.2, BA.4, and BA.5 variants was associated with a reduced risk for COVID-19-related hospitalization. The optimal neutralization titer thresholds that were predictive of COVID-19 hospitalizations were 96 (wild-type), 48 (delta), 12 (BA.1), 96 (BA.2), 96 (BA.4), and 48 (BA.5). CONCLUSIONS: BNT162b2-vaccine-induced neutralization responses are immune correlates of protection and confer clinical protection against COVID-19 hospitalizations.

Ticagrelor versus Prasugrel in Patients with Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention: Analysis from the Acute Coronary Syndrome Israeli Survey.

INTRODUCTION: We aimed to compare the outcomes of acute coronary syndrome (ACS) patients undergoing in-hospital percutaneous coronary intervention treated with prasugrel versus ticagrelor. METHODS: Among 7,233 patients enrolled to the Acute Coronary Syndrome Israeli Survey (ACSIS) between 2010 and 2018, we identified 1,126 eligible patients treated with prasugrel and 817 with ticagrelor. Comparison between the groups was performed separately in ST-elevation myocardial infarction (STEMI) patients, propensity score matched (PSM) STEMI patients, and non-ST-elevation ACS (NSTE-ACS) patients. RESULTS: In-hospital complication rates, including rates of stent thrombosis, were not significantly different between groups. In PSM STEMI patients, 30-day re-hospitalization rate (p < 0.05), 30-day MACE (the composite of death, MI, stroke, and urgent revascularization, p = 0.006), and 1-year mortality rates (p = 0.08) were higher in the ticagrelor group compared to the prasugrel group; in NSTE-ACS patients, outcomes were not associated with drug choice. In Cox regression analysis applied on the entire cohort, prasugrel was associated with lower 1-year mortality in STEMI patients but not in NSTE-ACS patients (p for interaction 0.03). CONCLUSIONS: Compared to ticagrelor, prasugrel was associated with superior clinical outcomes in STEMI patients, but not in NSTE-ACS patients.

PESI score for predicting clinical outcomes in PE patients with right ventricular involvement.

Pulmonary embolism (PE) patients with right ventricular (RV) involvement are a heterogenous group who mandate further risk stratification. Our objective was to evaluate the efficacy of the PE severity index (PESI) for predicting adverse clinical outcomes among PE patients with RV involvement. Consecutive normotensive PE patients with RV involvement were allocated according to admission PESI score (PESI ≤ III vs. PESI ≥ IV). The primary outcome included hemodynamic instability and in-hospital mortality. Secondary outcomes included each component of the primary outcome as well as mechanical ventilation, thrombolytic therapy, acute kidney injury, and major bleeding. Multivariable logistic regression model was performed to assess the independent association between the PESI score and primary outcome. C-Statistic was used to compare the PESI with the BOVA score. A total of 253 patients were evaluated: 95 (38%) with a PESI ≥ IV. Of them, 82 (32%) patients were classified as intermediate-low risk and 171 (68%) as intermediate-high risk. Fifty (20%) patients had at least 1 adverse event. Multivariate analysis demonstrated the PESI to be an independent predictor for the primary outcome (HR 4.81, CI 95%, 1.15-20.09, p = 0.031), which was increased with a concomitant increase of the PESI score (PESI I 4.2%, PESI II 3.4%, PESI III 12%, PESI IV 16.3%, PESI V 23.1%, p for trend < 0.001). C-Statistic analysis for the PESI score yielded an AUC-0.746 (0.637-0.854), p = 0.001, compared to the BOVA score: AUC-0.679 (0.584-0.775), p = 0.011. PESI score was found to predict adverse outcomes among normotensive PE patients with RV involvement.

Outcomes among patients admitted for non-ST-segment myocardial infarction in the pre-pandemic and pandemic COVID-19 era: Israel Nationwide study.

BACKGROUND: Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic in 2019, several countries have reported a substantial drop in the number of patients admitted with non-ST-segment myocardial infarction (NSTEMI). OBJECTIVE: We aimed to evaluate the changes in admissions, in-hospital management and outcomes of patients with NSTEMI in the COVID-19 era in a nationwide survey. METHOD: A prospective, multicenter, observational, nationwide study involving 13 medical centers across Israel aimed to evaluate consecutive patients with NSTEMI admitted to intensive cardiac care units over an 8-week period during the COVID-19 outbreak and to compare them with NSTEMI patients admitted at the same period 2 years earlier (control period). RESULTS: There were 624 (43%) NSTEMI patients, of whom 349 (56%) were hospitalized during the COVID-19 era and 275 (44%) during the control period. There were no significant differences in age, gender and other baseline characteristics between the two study periods. During the COVID-19 era, more patients arrived at the hospital via an emergency medical system compared with the control period (P = 0.05). Time from symptom onset to hospital admission was longer in the COVID-19 era as compared with the control period [11.5 h (interquartile range, IQR, 2.5-46.7) vs. 2.9 h (IQR 1.7-6.8), respectively, P < 0.001]. Nevertheless, the time from hospital admission to reperfusion was similar in both groups. The rate of coronary angiography was also similar in both groups. The in-hospital mortality rate was similar in both the COVID-19 era and the control period groups (2.3% vs. 4.7%, respectively, P = 0.149) as was the 30-day mortality rate (3.7% vs. 5.1%, respectively, P = 0.238). CONCLUSION: In contrast to previous reports, admission rates of NSTEMI were similar in this nationwide survey during the COVID-19 era. With longer time from symptoms to admission, but with the same time from hospital admission to reperfusion therapy and with similar in-hospital and 30-day mortality rates. Even in times of crisis, adherence of medical systems to clinical practice guidelines ensures the preservation of good clinical outcomes.

Systolic Time Intervals for Diagnosis of Severe Aortic Stenosis.

BACKGROUND: Estimated frequency of aortic stenosis (AS) in those over 75 years of age is 3.4%. Symptomatic patients with severe AS have increased morbidity and mortality and aortic valve replacement should be offered to improve life expectancy and quality of life. OBJECTIVES: To identify whether systolic time intervals can identify severe AS. METHODS: The study comprised 200 patients (mean age 79 years, 55% men). Patients were equally divided into normal, mild, moderate, or severe AS. All patients had normal ejection fraction. Acceleration time (AT) was defined as the time from the beginning of systolic flow to maximal velocity; ejection time (ET) was the time from onset to end of systolic flow. The relation of AT/ET was calculated. Death or aortic valve intervention were documented. AT increased linearly with the severity of AS, similar to ET and AT/ET ratio (P for trend < 0.05 for all). Receiver-operator characteristic curve analysis demonstrated that AT can identify severe AS with a cutoff ≥ 108 msec with 100% sensitivity and 98% specificity, while a cutoff of 0.34 when using AT/ET ratio can identify severe AS with 96% sensitivity and 94% specificity. Multivariate analysis adjusting to sex, stroke volume index, heart rate, and body mass index showed similar results. Kaplan-Meier curve for AT ≥ 108 and AT/ET ≥ 0.34 predicted death or aortic valve intervention in a 3-year follow-up. CONCLUSIONS: Acceleration time and AT/ET ratio are reliable measurements for identifying patients with severe AS. Furthermore, AT and AT/ET were able to predict aortic valve replacement or death.

Peripheral Arterial Disease in Patients With Acute Coronary Syndrome: Results From a Large Real-World Registry.

BACKGROUND: Limited data exist regarding the significance of peripheral arterial disease (PAD) in patients with acute coronary syndrome (ACS). METHODS: We evaluated 16,922 consecutive ACS patients who were prospectively included in a national ACS registry. The co-primary endpoint included 30 days major adverse cardiovascular event (MACE) (re-infarction, stroke, and/or cardiovascular death) and 1-year mortality. RESULTS: PAD patients were older (70±11 vs 63±13; p<0.01), male predominance (80% vs 77%; p=0.01), and more likely to sustain prior cardiovascular events. PAD patients were less likely to undergo coronary angiography (69% vs 83%; p<0.001) and revascularisation (80% vs 86%; p<0.001). Patients with PAD were more likely to sustain 30-day MACE (22% vs 14%; p<0.001) and mortality (10% vs 4.4%; p<0.001), as well as re-hospitalisation (23% vs 19%; p=0.001). After adjusting for potential confounders, PAD remained an independent predictor of 30-day MACE (odds ratio [OR], 1.6 [95% confidence interval (CI), 1.24-2.06]). Patients with compared to those without PAD had 2.5 times higher 1-year mortality rate (22% vs 9%; p<0.001). Co-existence of PAD remained an independent predictor of 1-year mortality after adjustment for potential confounders by multivariable regression analysis (OR, 1.62; 95% CI, 1.4-1.9). PAD was associated with a significant higher 1-year mortality rate across numerous sub-groups of patients including type of myocardial infarction (ST-elevation myocardial infarction vs non-ST-elevation myocardial infarction), and whether the patient underwent revascularisation. CONCLUSIONS: Acute coronary syndrome with concomitant PAD represents a high-risk subgroup that warrants special attention and a more tailored approach.

Illness perceptions of Israeli hospitalized patients with acute coronary syndrome.

BACKGROUND: Illness perceptions (IPs) can affect cardiac health behaviours and outcomes. AIMS AND OBJECTIVES: To investigate IPs among patients hospitalized with acute coronary syndrome (ACS). DESIGN: Longitudinal survey. METHODS: The ACS Israel Study is a national, biennial registry, enrolling all patients with ACS admitted to cardiac intensive care or cardiology wards in Israel within a 2-month period. Data includes demographics, medical history, and treatment for ACS using an electronic database. In 2018, a nursing component was added, including the Brief Illness Perception Questionnaire. Data were analysed using descriptive statistics and a two-stage cluster analysis. RESULTS: A total of 990 subjects were surveyed. Mean age was 62.8 (SD = 12.5) and most respondents were male and married. Mean IP scores ranged from 3.28 to 6.06. Three clusters were found; one only of women and two only of men (one cluster with lower IPs and little previous medical history and cardiac risk factors and the second with higher IPs, greater medical history, and cardiac risk factors. Those with higher education scored lower on several IPs. CONCLUSIONS: Subjects were moderately cognitively and emotionally impacted by their illness. Men tended to perceive their illness as having either a relatively strong or a relatively weak emotional and cognitive impact on their lives, where women were somewhere in-between. Participants with an academic education perceived less of an impact of the illness while those with a previous history of chronic disease reported the opposite. It is recommended that educational interventions and in-depth qualitative studies be designed that investigate the development of IPs during hospitalization to potentially improve cardiac health behaviours, especially among those without a previous medical history and cardiac risk factors. RELEVANCE TO CLINICAL PRACTICE: Those without a history of chronic disease or a lower level of education are less likely to absorb the full impact of a cardiac event while hospitalized and should, therefore, be monitored more closely and coached with greater intensity than other groups while still in-hospital.

Distress among hospitalized patients with acute coronary syndrome.

BACKGROUND: Previous studies have demonstrated that those suffering from acute coronary syndrome (ACS) experience various physical and psychological symptoms. Few studies have investigated the multi-factorial, holistic, unpleasant experience of distress that includes physical, psychological, social, and spiritual factors among this patient population while still hospitalized. AIM: To describe the level of distress among patients hospitalized with ACS and its association with demographic and clinical factors and mortality. STUDY DESIGN: The study conducted a descriptive, cross-sectional survey. METHODS: The Acute Coronary Syndrome Israel Study is a national, biennial registry, enrolling all patients with ACS admitted to cardiac intensive care or cardiology wards in Israel within a 2-month period. Demographic and clinical data were retrieved from an electronic database. Distress was measured by the Distress Thermometer. Nurses collected distress data directly from patients before discharge. RESULTS: Nine hundred ninety participants (50.6% response rate) were surveyed. Mean age was 62.8 (SD = 12.5). Mean distress level was 4.8 (SD = 3.45) out of 10. The most frequently reported area of distress was physical, followed by emotional. Practical and family problems were less frequent. Emotional distress was found to differ based on educational level, marital status, smoking history, and previous medical history. Distress did not predict 7- or 30-day mortality. CONCLUSIONS: Respondents with ACS were in moderate distress. It is recommended that those at increased risk receive increased monitoring of emotional distress while still in hospital. Further studies should investigate this holistic view of distress among the ACS population using a variety of methods and methodologies.

Association of Polycythemia with Outcomes of Acute Coronary Syndrome.

BACKGROUND: Polycythemia has not been extensively studied for its impact on acute coronary syndrome (ACS) outcomes. A previous study reported only 30-day outcomes to be worse in these patients. METHODS: Data from the ACS Israeli survey between 2000 and 2018 were utilized to compare between 3 groups of patients with ACS: anemic group (hemoglobin <12 g/dL for women and <12.5 g/dL for men), normal hemoglobin group, and polycythemic group (>16 g/dL and >16.5 g/dL, respectively). Measured outcomes included 30-day major adverse cardiac events (MACE comprising all-cause mortality, recurrent ACS, need for urgent revascularization, and stroke) and 1- and 5-year all-cause mortality. RESULTS: Of 14,746 ACS patients, 10,752 (72.9%) had normal hemoglobin levels, 3,492 (23.7%) were anemic, and 502 (3.4%) were polycythemic. In comparison with normal and anemic patients, polycythemic patients were younger (55.9 ± 10.5 vs. 61.9 ± 12.4 and 71.1 ± 12.2 for anemic, respectively, p < 0.001 for both), more frequently men (93.8% vs. 81.3% and 63.1%, respectively, p < 0.001), and less likely diabetic or hypertensive. Upon adjustment to baseline characteristics, compared with normal hemoglobin, polycythemia was not independently associated with 30-day MACE or 1-year mortality, but it was independently associated with higher risk for 5-year mortality (HR 1.76, 95% CI: 1.19-2.59, p = 0.005). Similar results were observed after propensity score matching. CONCLUSIONS: Although younger and with fewer comorbidities, polycythemic ACS patients are at increased risk for long-term all-cause mortality. Further study of this association is warranted to understand the causes and possibly to improve the outcomes of these patients.

Bicuspid aortic valve area in normal heart.

INTRODUCTION: Bicuspid aortic valve (BAV) is a common congenital valve abnormality. There are no data in the literature regarding the range of aortic valve area (AVA) in normal functioning BAV. We aimed to evaluate the normal range of BAV area and to compare it to subjects with tricuspid aortic valve (TAV). METHODS: Bicuspid aortic valve subjects were identified from Sheba medical center echocardiographic database and were compared with TAV subjects. Inclusion criteria were normal tissue leaflets appearance and normal functioning valve in the presence of normal echocardiogram. Echocardiographic data, patients hemodynamics, and size were collected. AVA was measured with both planimetry and the continuity equation. RESULTS: Fifty BAV and 50 control subjects were studied (37 men, age 40 ± 13 years). All studies were performed with normal hemodynamics. Fusion between the coronary leaflets was the most common morphology (82%), followed by fusion between the right coronary leaflet with the noncoronary leaflet (18%). The left ventricular outflow tract (LVOT) diameter in BAV group was significantly larger (2.3 ± 0.3 cm vs 2.1 ± 0.2; P < .001). The BAV group presented with a larger AVA planimetry (3.8 ± 0.9 vs 3.3 ± 0.6; P < .001). However, measuring AVA using continuity equation has shown no differences between groups. If using the principles of coefficient of contraction, it seems that measuring AVA by planimetry overestimates the real anatomic AVA. CONCLUSION: This data provide normal values for echocardiographically determined AVA in BAV subjects. This population was characterized by large LVOT diameter and large AVA. The larger AVA measured with the planimetry emphasizes the limitation of this method in BAV population.

The Aspirin Primary Prevention Conundrum.

BACKGROUND: In this review, the authors re-examine the role of aspirin in the primary prevention of cardiovascular disease. They discuss the history of the use of aspirin in primary prevention, the current guidelines, and the recent evidence surrounding aspirin use as primary prevention in special populations such as those with moderate cardiovascular risk, diabetes mellitus, and the elderly.

Degenerative Mitral Regurgitation: Assessment, Physical Examination, and Imaging.

PURPOSE OF REVIEW: In this review, we provide a comprehensive approach to assess degenerative mitral regurgitation. RECENT FINDINGS: In the evaluation of MR, it is important to differentiate between primary (degenerative/organic) MR in which an intrinsic mitral valve lesion(s) is responsible for the occurrence of MR and secondary (functional) MR where the mitral valve is structurally normal, but alterations of the left ventricular geometry cause deterioration of the MV apparatus. Advanced imaging modalities, foremost two-dimensional and three-dimensional echocardiography, are essential for this determination. In the evaluation of degenerative MR, the exact mechanism, the extent of the disease, associated valve lesions, the grade of mitral regurgitation severity, and hemodynamic consequences require careful assessment in order to provide patients with appropriate monitoring and treatment.

Aortic Regurgitation.

PURPOSE OF REVIEW: Aortic regurgitation (AR) is a common form of valvular disease which is characterized by reflux of blood from the aorta into the left ventricle (LV) during diastole. AR results from various etiologies, affecting the aortic valve cusps or the aortic root. The clinical presentation of patients with AR depends on the severity of the regurgitation and differs whether AR develops acutely or if it progresses over a prolonged period, allowing the cardiac chambers to adapt. Echocardiography is the primary method to determine the etiology of AR and to define its severity. We review the current data regarding the diagnosis and treatment of AR. RECENT FINDINGS: No single parameter is sufficient to determine AR severity; thus, an integrative, multi-parametric approach is required. Echocardiography is key for imaging the aortic valve morphology and flow as well as aortic root and ascending aorta. Determining LV ejection fraction and dimensions is essential for patient management and optimizing timing for intervention. Three-dimensional (3D) echocardiography is useful in the evaluation of AR etiology and severity. The use of Trasncatheter aortic valve replacement (TAVR) has emerged as an alternative to surgery in patients at high operative risk. The diagnosis and management of AR requires a comprehensive approach and routine clinical and echocardiographic follow-up. Surgical or percutaneous therapy is indicated when symptoms develop and in those who have LV dysfunction or LV dilation.

[PLATELETS FUNCTION IN A DROP OF BLOOD: FLOW CYTOMETRY ANALYSIS COMPARED TO PLATELET AGGREGATION].

INTRODUCTION: Light transmission aggregometry (LTA) is the most commonly used test for the diagnosis of platelet function disorders, but requires large amounts of blood samples and normal platelet count. OBJECTIVES: To compare flow cytometric (FC) platelet function testing to standard LTA in the general population, in patients treated with anti-platelets drugs and in term and preterm neonates. METHODS: Platelet function was assessed with LTA and FC using PAC1 binding and p-selectin expression, as platelet activation markers, in response to agonist activation. A comparison between LTA and FC was performed in a Clopidogrel treated patient, before and after (24 and 72 hours) loading the drug. The platelet activation markers PAC1 and p-selectin, were compared in umbilical cord blood samples of in-term and preterm neonates. RESULTS: ADP-induced platelet aggregation was comparable to p-selectin expression assayed by FC (r=0.79-0.86) as measured before and after Clopidogrel loading. Both tests showed good response to Clopidogrel in 72 hours but not in 24 hours after its loading. Preterm cord blood platelets showed decreased ADP-induced activation in both activation markers: PAC1 and p-selectin, but only p-selectin reached statistical significance. We identified possible platelet activation markers in response to commonly used agonists' stimulation for FC analysis. CONCLUSIONS: FC analysis of platelet function has added value in the diagnosis of impaired platelet function and anti-platelet drug response. Using FC enables us to test platelet function in minimal blood volume and regardless of platelet count. Identification of the unique activation marker for each agonist is prerequisite for FC analysis of platelet function.

The "Burden" of Malignancy in a Tertiary Hospital Intensive Cardiovascular Care Unit.

OBJECTIVES: During the past decade, the most common causes of mortality and morbidity were cardiovascular diseases and malignancies. The aim of the current study was to describe the incidence, course of admission, and short-term (30-day) prognosis of patients with and without malignancy, admitted to a tertiary center intensive cardiovascular care unit (ICCU). METHODS: A prospective observational study of 2,259 patients admitted to the ICCU was conducted between January 2014 and December 2015. Patients with malignancies (n = 256) were divided into 2 groups: those with solid and those with homogenous tumors. RESULTS: The time of diagnosis was categorized into 3 patient groups: recent (<6 months), 59 patients (23%); late (6-24 months), 49 patients (19%), and very late (>24 months), 148 patients (58%). Those with a history of malignancy were older (73 ± 12 vs. 64 ± 15, p < 0.001) and were more likely to be female (p = 0.002). After using a multivariate logistic regression model analysis, no differences were found in therapeutic interventions and clinical outcomes, including major bleeding and acute renal failure, between patients with and without malignancies. CONCLUSIONS: Patients with a malignancy comprised about 10% of the entire ICCU population. While mortality was independently associated with advanced age, renal failure, and a diagnosis of ST-elevation myocardial infarction, malignancy alone was not found to be independently associated with a higher mortality rate at 30 days of follow-up.

Real-World Use of Novel P2Y12 Inhibitors in Patients with Acute Myocardial Infarction: A Treatment Paradox.

OBJECTIVE: To assess the real-world use, clinical outcomes, and adherence to novel P2Y12 inhibitors. METHODS: We evaluated 1,093 consecutive acute myocardial infarction patients undergoing a percutaneous intervention. Patients were derived from a prospective, multicenter, nationwide registry and were followed for 30 days; 381 patients (35%) received clopidogrel, 468 (43%) received prasugrel, and 244 (22%) received ticagrelor. Patients treated with clopidogrel were older and more likely to suffer from chronic renal failure and stroke and/or present with non-ST-elevation myocardial infarction (NSTEMI) (p < 0.01 for all). Independent predictors of undertreatment with novel P2Y12 inhibitors included: older age (OR 0.17; 95% CI 0.1-0.27, p < 0.0001), a prior stroke (OR 0.41; 95% CI 0.2-0.68, p = 0.008), and NSTEMI (OR 0.37; 95% CI 0.26-0.54, p < 0.0001). RESULTS: Novel P2Y12 inhibitors were associated with a lower incidence of cardiovascular events, major bleeding, and/or death (7.6 vs.11%, HR 0.67; 95% CI 0.43-1, p = 0.05). However, after a multivariate analysis this trend was not statistically significant. Patients discharged with ticagrelor versus thienopyridines demonstrated a higher rate of crossover to other P2Y12 inhibitors (11 vs. 5%, p = 0.03). CONCLUSIONS: In a real-world cohort, there was an underutilization of novel P2Y12 inhibitors which was more pronounced in higher-risk subsets that might benefit from novel P2Y12 inhibitors at least as much as other patients.

Evaluation of Patients with Acute Chest Pain Using SPECT Myocardial Perfusion Imaging: Prognostic Implications of Mildly Abnormal Scans.

BACKGROUND: While patients presenting to emergency departments (ER) with chest pain are increasingly managed in chest pain units (CPU) that utilize accelerated diagnostic protocols for risk stratification, such as single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI), data are lacking regarding the prognostic implications of mildly abnormal scans in this population. OBJECTIVES: To evaluate the prognostic implications of mildly abnormal SPECT MPI results in patients with acute chest pain. METHODS: Of the 3753 chest pain patients admitted to the CPU at the Leviev Heart Center, Sheba Medical Center 1593 were further evaluated by SPECT MPI. Scans were scored by extent and severity of stress-induced perfusion defects, with 1221 patients classified as normal, 82 with myocardial infarction without ischemia, 236 with mild ischemia, and 54 with more than mild ischemia. Mild ischemia patients were further classified to those who did and did not undergo coronary angiography within 7 days. RESULTS: Mild ischemia patients who underwent coronary angiography were more likely to be male (92% vs. 81%, P = 0.01) and to have left anterior descending ischemia (67% vs. 42%, P = 0.004). After 50 months, these patients returned less often to the ER with chest pain (53% vs. 87%, P < 0.001) and had a lower combined endpoint of acute coronary syndrome and death (8% vs. 16%, P < 0.001). CONCLUSIONS: Compared to patients with chronic stable angina, patients presenting with acute chest pain exhibiting mildly abnormal SPECT MPI findings should perhaps undergo a more aggressive diagnostic and therapeutic approach.

The Role of Medical Therapy in Moderate to Severe Degenerative Mitral Regurgitation.

Mitral regurgitation (MR) is a common valvular disorder that has important health and economic consequences. Standardized guidelines exist regarding when and in whom to perform mitral valve surgery, but little information is available regarding medical treatment of MR. Many patients with moderate or severe MR do not meet criteria for surgery or are deemed to be at high risk for surgical therapy. We reviewed the available published data on medical therapy in the treatment of patients with primary MR. b-blockers and renin-angiotensin-aldosterone system inhibitors had the strongest supporting evidence for providing beneficial effects. b-blockers appear to lessen MR, prevent deterioration of left ventricular function, and improve survival in asymptomatic patients with moderate to severe primary MR. Angiotensin-converting enzyme inhibitor and angiotensin receptor blocker therapy reduces MR, especially in asymptomatic patients. However, in the setting of hypertrophic cardiomyopathy or mitral valve prolapse, vasodilators can increase the severity of MR. To define the precise role of medical therapy, a larger randomized controlled trial is needed to confirm benefit and assess in which subsets of patients medical therapy is most useful. Medical therapy in some patients improves symptoms, lessens MR, and may delay the need for surgical intervention.

Evaluation of platelet response to different clopidogrel dosing regimens in patients with acute coronary syndrome in clinical practice.

High-post clopidogrel platelet reactivity in acute coronary syndrome (ACS) patients is associated with adverse outcomes and may be related to clopidogrel dosing. Clinical studies evaluating different clopidogrel doses have resulted in conflicting conclusions. Clopidogrel dosing regimens have evolved over time, enabling us to evaluate platelet reactivity in real-life ACS patients undergoing percutaneous coronary intervention and treated with three different clopidogrel doses. Platelet reactivity was assessed with light transmitted aggregometry on the third day post clopidogrel loading in 404 consecutive ACS patients. Of them, 198 were treated with a standard regimen (300 mg loading, 75 mg/day maintenance dose), 95 with a high loading regimen (600 mg loading, 75 mg/day maintenance dose) and 111 with a high loading/high maintenance regimen (600 mg loading, 150 mg/day maintenance). Compared with the standard regimen, the high loading regimen resulted in significantly lower mean platelet reactivity to adenosine diphosphate (ADP) with a lower proportion of patients exhibiting clopidogrel non-responsiveness (11% vs. 28%, p = 0.004). Compared with the high loading regimen, the high loading/high maintenance regimen resulted in significantly lower mean platelet reactivity to ADP, but without a further drop in the number of non-responders (8.1% vs. 11%, p = 0.16). In conclusion, greater overall inhibition can be achieved with higher loading and maintenance doses in ACS patients. However, despite high clopidogrel doses, a sizable proportion of patients remained "resistant" to the effects of clopidogrel.

Echo Doppler Estimation of Pulmonary Capillary Wedge Pressure in Patients with Severe Aortic Stenosis.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) has become a treatment option for patients with severe aortic stenosis (AS) and high surgical risk. Assessment of symptoms in these patients is challenging because of advanced age, comorbidities, and limited physical activity. Noninvasive quantification of pulmonary capillary wedge pressure (PCWP) in candidates for TAVR may be helpful for risk stratification. The objective of the study was to create a model for estimation of PCWP by echo Doppler in patients with severe AS. METHODS AND RESULTS: Data from 80 patients with severe AS referred for TAVR were used to develop an echo Doppler model for predicting PCWP. Its performance was evaluated in the test cohort of 33 patients who had invasive and noninvasive evaluation. No single echo Doppler parameter estimated PCWP accurately. In the retrospective analysis, the multilinear regression provided an accurate estimate of PCWP (r(2) = 0.74). The model included, in order of importance (all P < 0.05), the ratio of early transmitral velocity (E) to annular velocity (E'), the left ventricular ejection fraction, and the velocity time integral of tricuspid regurgitation signal. In the prospective cohort of patients with severe AS, the model demonstrated good predictive ability of PCWP (r = 0.77, P < 0.01). CONCLUSION: In patients with severe AS, noninvasive estimation of PCWP is possible by integration of two-dimensional, spectral, and tissue Doppler variables.