Selected Abstracts

Title: Heart Rate Recovery and Chronotropic Incompetence in Patients with Subclinical Hypothyroidism

Background: Heart rate recovery (HRR) and chronotropic incompetence (CI) in patients with subclinical hypothyroidism (SCH) has not been explored previously. The aim of the present study was to evaluate the HRR and CI in patients with SCH.
Methods: Twenty-five patients (11 men, 14 women with a mean age of 36±10 years) who were diagnosed SCH determined by an increased serum thyrothrophine (TSH) concentration (>4.0 ng/mL) and the normal free triiodothyronine (fT3) and free thyroxin (fT4) levels, were included in the study. The control group of healthy individuals with normal TSH (12 males, 15 females) with a mean age of 36 ± 3 years was also included. Two groups were well matched for age, sex, and body mass index. Medical history, physical examination, electrocardiogram, treadmill exercise testing, and chest radiogram were performed for all participants.
Results: The characteristics of SCH patients and control cases were similar with regard to age, sex, and BMI except for TSH levels. Serum TSH levels were significantly higher in SCH patients than the controls (P < 0.001). No significant differences were observed in the changes of heart rate (HR), exercise tolerance (metabolic equivalents), or systolic and diastolic blood pressures at rest or during exercise between the groups, whereas HRR and CI were significantly lower during exercise testing in the SCH patients compared to controls (P < 0.003; P < 0.03, respectively).
Conclusion: The results of the present study demonstrated that SCH can cause impaired cardiovascular autonomic function and attenuated HR response to exercise. (PACE 2010; 33:2-5)

Title: Cardiovascular Outcomes and Mortality in Patients Using Clopidogrel With Proton Pump Inhibitors After Percutaneous Coronary Intervention or Acute Coronary Syndrome.

AB Background-: Recent studies have raised concerns about the reduced efficacy of clopidogrel when used concurrently with proton pump inhibitors (PPIs), but those studies may have overestimated the risk. Methods and Results-: We studied the potential for increased risk of adverse cardiovascular events among users of clopidogrel with versus without concurrent use of PPIs in 3 large cohorts of patients >=65 years of age, treated between 2001 and 2005. All patients had undergone percutaneous coronary intervention or had been hospitalized for acute coronary syndrome in Pennsylvania, New Jersey, or British Columbia, and subsequently had initiated treatment with clopidogrel. We recorded myocardial infarction hospitalization, death, and revascularization among PPI users and nonusers. We assessed our primary end point of myocardial infarction hospitalization or death using cohort-specific and pooled regression analyses. We entered 18 565 clopidogrel users into our analysis. On a pooled basis, 2.6% of those who also initiated a PPI versus 2.1% of PPI nonusers had a myocardial infarction hospitalization; 1.5% versus 0.9% died; and 3.4% versus 3.1% underwent revascularization. The propensity score-adjusted rate ratio for the primary end point of myocardial infarction or death was 1.22 (95% confidence interval, 0.99 to 1.51); for death, 1.20 (95% confidence interval, 0.84 to 1.70); and for revascularization, 0.97 (95% confidence interval, 0.79 to 1.21). Matched analyses generally yielded similar results. Conclusions-: Although point estimates indicated a slightly increased risk of myocardial infarction hospitalization or death in older patients initiating both clopidogrel and a PPI, we did not observe conclusive evidence of a clopidogrel-PPI interaction of major clinical relevance. Our data suggest that if this effect exists, it is unlikely to exceed a 20% risk increase. (C) 2009 American Heart Association, Inc.
Circulation dec 2009

Title: AF in Acute MI

Background: Atrial fibrillation (AF) is associated with increased mortality and a higher complication rate postmyocardial infarction (MI), but the exact mechanisms are unknown. We investigated whether AF predisposes to ventricular arrhythmia in postmyocardial infarct patients, thereby accounting for increased mortality.

Methods: Five hundred consecutive patients admitted to our coronary care unit with acute MI were monitored for in-hospital arrhythmias. Detailed information was also compiled on past history, co-morbidities, electrolyte disturbances, drug therapies, and ejection fraction. Mortality data were collected for an average of 5.5 years.

Results: The results have shown that the incidence of ventricular fibrillation (VF) is much greater in patients presenting with AF (P = 0.03) and multivariate analysis has shown that AF is independently associated with the development of VF. This association occurs principally in patients who are admitted with AF (P = 0.01) rather than those who develop it during their admission, although these patients are also at mildly increased risk. The increased incidence of VF does account for increased mortality in the AF patients but does not explain all of their excess risk. There was no association between AF and ventricular tachycardia (VT); P = 0.50.

Conclusions: In conclusion, AF on admission to the hospital with acute MI is associated with an increased risk of VF and subsequent mortality. (PACE 2008; 31:1612-1619)

Title: Electrocardiogram voltage discordance: interpretation of low QRS voltage

Abstract Introduction: Low voltage on the surface electrocardiogram (ECG) is defined as QRS voltage less than 5 mm in all limb leads and less than 10 mm in all precordial leads. The clinical correlate of an ECG with low voltage in the limb leads but normal precordial QRS amplitudes is unclear.

Methods: Twelve-lead ECGs with QRS voltage less than 5 mm in all limb leads and more than 10 mm in at least 2 contiguous precordial leads were collected. Presence of clinical conditions associated with low voltage was determined from clinical data and chest imaging.

Results: Fifty-one of 100 patients had voltage discordant ECGs that correlated with conditions known to cause diffuse low voltage. Among those without associated conditions, 63% had dilated ventricles, with an average ejection fraction of 33%.

Conclusions: Low voltage isolated to the limb leads is associated with the same conditions that cause diffuse low voltage in only half of patients. In the remainder, more than 60% have dilated cardiomyopathies.

Title: Impact of Red Blood Cell Transfusion on Clinical Outcomes in Patients With Acute Myocardial Infarction

Divergent views remain regarding the safety of treating anemia with red blood cell (RBC) transfusion in patients with acute coronary syndrome (ACS). We used a prospective database to study effect of RBC transfusion in patients with acute myocardial infarction (MI; n _ 2,358). Cox regression models were used to determine the association between RBC transfusion and 6-month outcomes, incorporating transfusion as a time-dependent variable. The models adjusted for baseline variables, propensity for transfusion, and nadir hemoglobin previous to the transfusion. One hundred ninety-two patients (8.1%) received RBC transfusion. Six-month mortality rates were higher in patients receiving transfusion (28.1% vs 11.7%, p <0.0001). The adjusted hazard ratio (HR) for mortality was 1.9 in transfused patients (95% confidence interval [CI] 1.3 to 2.9). Interaction between RBC transfusion and nadir hemoglobin with respect to mortality (p _ 0.004) was significant. Stratified analyses showed a protective effect of transfusion in patients with nadir hemoglobin <8 g/dL (adjusted HR 0.13, 95% CI 0.03 to 0.65, p _ 0.013). By contrast, transfusion was associated with increased mortality in patients with nadir hemoglobin >8 g/dL (adjusted HR 2.2, 95% CI 1.5 to 3.3; p <0.0001). Similar results were obtained for the composite end point of death/MI/heart failure (p for interaction _ 0.04). In conclusion, RBC transfusion in patients with acute MI and hemoglobin <8 g/dL may be appropriate. The increased mortality observed in transfused patients with nadir hemoglobin above 8 g/dL underscores the clinical difficulty of balancing risks and benefits of RBC transfusion in the 

setting of ACS. © 2008 Elsevier Inc. All rights reserved. (Am J Cardiol 2008;102:115-119)

Title: Value of lead aVR in predicting acute occlusion of proximal left anterior

Abstract Background: We aimed to investigate the value of ST elevation in lead aVR (STaVR) in predicting the left anterior descending coronary artery (LAD) occlusion site proximal to first septal perforator (S1) and its effect on in-hospital outcome in ST-elevation myocardial infarction (STEMI).

Methods: The study included 950 patients with STEMI. Patients were divided into 2 groups as aVR (+) and aVR() according to the presence of an STaVR of 0.5 mm or greater.

Results: ST elevation in lead aVR was seen in 155 (16%) patients, and LAD occlusion proximal to S1 was detected in 52% of patients in the aVR(+) group and in 9% of patients in the aVR() group. aVR positivity was associated with higher heart rate, lower systolic blood pressure and ejection fraction, and worse Killip class at the hospital admission. In-hospital mortality was 19% in the aVR(+) group and 5% in the aVR() group. aVR positivity was an independent predictor of in-hospital death.

Conclusion: This study revealed that STaVR was not only a good indicator of LAD occlusion proximal to S1 but also a source of valuable information about in-hospital outcome in patients with STEMI.

Title: Influence of Beta-Blocker continuation or withdrawal on outcomes in patients hospitalized With Heart Failure

Objectives: This study ascertains the relationship between continuation or withdrawal of beta-blocker therapy and clinical outcomes in patients hospitalized with systolic heart failure (HF).

Background: Whether beta-blocker therapy should be continued or withdrawn during hospitalization for decompensated HF has not been well studied in a broad cohort of patients.

Methods: The OPTIMIZE-HF (Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure) program enrolled 5,791 patients admitted with HF in a registry with pre-specified 60- to 90-day follow-up at 91 academic and community hospitals throughout the U.S. Outcomes data were prospectively collected and analyzed according to whether beta-blocker therapy was continued, withdrawn, or not started.

Results: Among 2,373 patients eligible for beta-blockers at discharge, there were 1,350 (56.9%) who were receiving beta-blockers before admission and continued on therapy, 632 (26.6%) newly started, 79 (3.3%) in which therapy was withdrawn, and 303 (12.8%) eligible but not treated. Continuation of beta-blockers was associated with a significantly lower risk and propensity adjusted post-discharge death (hazard ratio [HR]: 0.60; 95% confidence interval [CI]: 0.37 to 0.99, p _ 0.044) and death/rehospitalization (odds ratio: 0.69; 95% CI: 0.52 to 0.92, p _ 0.012) compared with no beta-blocker. In contrast, withdrawal of beta-blocker was associated with a substantially higher adjusted risk for mortality compared with those continued on beta-blockers (HR: 2.3; 95% CI: 1.2 to 4.6, p _ 0.013), but with similar risk as HF patients eligible but not treated with beta-blockers.

Conclusions: The continuation of beta-blocker therapy in patients hospitalized with decompensated HF is associated with lower post-discharge mortality risk and improved treatment rates. In contrast, withdrawal of beta-blocker therapy is associated with worse risk and propensity-adjusted mortality.

 (Organized Program To Initiate Lifesaving Treatment In Hospitalized Patients With Heart Failure [OPTIMIZE-HF]; NCT00344513) (J Am Coll Cardiol 2008; 52:190-9) © 2008 by the American College of Cardiology Foundation

Title: Carotid Artery Revascularization in High-Surgical-Risk Patients Using the Carotid WALLSTENT and FilterWire EX/EZ

Objectives :The multicenter, single-arm BEACH (Boston Scientific EPI: A Carotid Stenting Trial for High-Risk Surgical Patients) evaluated outcomes in high-surgical-risk patients with carotid artery stenosis treated with the Carotid WALLSTENT plus FilterWire EX/EZ Emboli Protection System (Boston Scientific, Natick, Massachusetts).

Background :Carotid artery stent (CAS) placement offers a less invasive alternative for high-risk surgical carotid endarterectomy (CEA) patients.

 Methods: The trial enrolled 480 pivotal patients who were candidates for carotid revascularization but considered high surgical risk due to pre-specified anatomic criteria and/or medical comorbidities. The primary end point (all stroke, death, or Q-wave myocardial infarction [MI] through 30 days; non-Q-wave MI through 24 h; and ipsilateral stroke or neurologic death through 1 year) was compared with a proportionally weighted objective performance criterion (OPC) of 12.6% for published surgical endarterectomy results in similar patients, plus a pre-specified noninferiority margin of 4%.

Results :Among pivotal patients, 41.2% were at high surgical risk due to comorbid risk factors, and 58.8% due to anatomic risk factors; 76.7% were asymptomatic with flow-limiting carotid stenosis 80%. At 1 year, the composite primary end point occurred in 8.9% (40 of 447), with a repeat revascularization rate of 4.7%. With an upper 95% confidence limit of 11.5% for the primary composite end point, the BEACH trial results met the prespecified criteria for noninferiority relative to the calculated OPC plus noninferiority margin (16.6%) for historical surgical CEA outcomes in similar patients (p  0.0001 for noninferiority).

Conclusions: The BEACH trial results demonstrate that CAS with the WALLSTENT plus FilterWire embolic protection is noninferior (equivalent or better than) to CEA at 1-year in high-surgical-risk patients (Boston Scientific Embolic Protection, Inc. [EPI]: A Carotid Stenting Trial for High-Risk Surgical Patients [BEACH]; http://clinicaltrials.gov/ct2/ show/NCT00316108?termNCT00316108&rank1; NCT00316108).

Title: Mitral Regurgitation Augments Post-Myocardial Infarction Remodeling

Objectives We examined whether mitral regurgitation (MR) augments post-myocardial infarction (MI) remodeling.

Background MR doubles mortality after MI, but its additive contribution to left ventricular (LV) remodeling is debated and has not been addressed in a controlled fashion.

Methods Apical MIs were created in 12 sheep, and 6 had an LV-to-left atrial shunt implanted, consistently producing regurgitant fractions of 30%.the groups were compared at baseline,1 and 3 months.  .

Results Left ventricular end-systolic volume progressively increased by 190% with MR versus 90% without MR (p 0.02). Pre-load-recruitable stroke work declined by 82  13% versus 25  16% (p 0.01) with MR, with decreased remote-zone sarcoplasmic reticulum Ca2-ATPase levels (0.56  0.03 vs. 0.76  0.02, p 0.001), and decreased isolated myocyte contractility. In remote zones, pro-hypertrophic Akt and gp130 were upregulated in both groups at 1 month, but significantly lower and below baseline in the MR group at 3 months. Pro-apoptotic caspase 3 remained high in both groups. Matrix metalloproteinase (MMP)-13 and membrane-type MMP-1 were increased in remote zones of MR versus infarct-only animals at 1 month, then fell below baseline. The MMP tissue inhibitors rose from baseline to 3 months in all animals, rising higher in the MI  MR-group border zone.

Conclusions In this controlled model, moderate MR worsens post-MI remodeling, with reduced contractility. Pro-hypertrophic pathways are initially upregulated but subsequently fall below infarct-only levels and baseline; with sustained caspase 3 elevation, transformation to a failure phenotype occurs. Extracellular matrix turnover increases in MR animals. Therefore, MR can precipitate an earlier onset of dilated heart failure.

Title: Relation Between Stress-Induced Myocardial Perfusion Defects on Cardiovascular Magnetic Resonance and Coronary Microvascular Dysfunction in Patients With Cardiac Syndrome X

Objectives: The purpose of this study was to investigate whether a direct relation can be demonstrated between myocardial perfusion defects detected during dobutamine stress test (DST) by cardiovascular magnetic resonance (CMR) and impairment of coronary mcrovascular dilatory function in patients with cardiac syndrome X (CSX).

Background: Despite the fact that coronary microvascular dysfunction has been shown in most patients with CSX, the ischemic origin of CSX remains debated. No previous study assessed whether a strict relation exists between abnormalities in myocardial perfusion and coronary microvascular dysfunction in CSX patients.

Methods: Eighteen CSX patients (mean age 58  7 years, 7 men) and 10 healthy control subjects (mean age 54 years, 4 men) underwent myocardial perfusion study by gadolinium-enhanced CMR at rest and at peak DST (maximal dose 40 g/kg/min). Coronary flow response (CFR) to adenosine (140 g/kg/min in 90 s) in the left anterior descending (LAD) coronary artery was assessed by high-resolution transthoracic echo-Doppler and expressed as the ratio between coronary flow velocity at peak adenosine and at rest.

Results: At peak DST, reversible perfusion defects on CMR were found in 10 CSX patients (56%) but in none of the control subjects (p 0.004). The CFR to adenosine in the LAD coronary artery was lower in CSX patients than in control subjects (2.03  0.63 vs. 3.29  1.0, p 0.0004). The CSX patients with DST-induced myocardial perfusion defects in the LAD territory on CMR had a lower CFR to adenosine compared with those without perfusion defects in the LAD territory (1.69  0.5 vs. 2.31  0.6, p 0.01). A significant correlation was found in CSX patients between CFR to adenosine and a DST perfusion defect score on CMR in the LAD territory (r0.45, p 0.019).

Conclusions: Our data concurrently show DST-induced myocardial perfusion defects on CMR and reduced CFR in the LAD coronary artery territory in CSX patients, thus giving strong evidence that a dysfunction of coronary microcirculation resulting in myocardial perfusion abnormalities is present in these patients.

Title: Secondary Prevention With Bezafibrate Therapy for the Treatment of Dyslipidemia

Objectives This study was designed to evaluate the long-term cardiovascular benefit of bezafibrate therapy in coronary heart disease patients enrolled in the BIP (Bezafibrate Infarction Prevention) trial.

Background The BIP trial yielded a nonsignificant 7.3% reduction in the rate of major cardiac events after a mean follow-up period of 6.2 years, possibly owing to an increasing unbalanced usage of nonstudy lipid-lowering drugs (LLDs) during the course of the trial.

Methods The adjusted risk for the combined end point of cardiac death or nonfatal myocardial infarction during an extended mean 8.2-year follow-up period of the BIP trial was assessed in 3,090 patients allocated to the original bezafibrate (n  1,548) and placebo (n  1,542) groups of the trial.

Results During the extended follow-up period, nonstudy LLDs were administered to a significantly greater proportion of placebo-allocated patients (57%) than bezafibrate-allocated patients (53%; p  0.02). Interaction-term analysis demonstrated that the benefit of bezafibrate therapy was pronounced (18% risk reduction; p  0.03) without or before treatment with nonstudy LLDs initiated during follow-up and attenuated (hazard ratio 1.05; p  0.85) after therapy with nonstudy LLDs initiated during the observation period. Consistent with these findings, treatment with bezafibrate was shown to be associated with a significant 17% risk reduction (p  0.03) when study patients were censored from the analysis upon initiation of therapy with nonstudy LLDs.

Conclusions The data demonstrate that bezafibrate therapy in the BIP trial was associated with significant long-term cardiovascular protection that was attenuated by an unbalanced usage of nonstudy LLDs during the course of the trial.