Previous studies evaluating the influence of time to reperfusion on infarct size (IS) and myocardial salvage in patients with ST-segment elevation myocardial infarction (STEMI) have yielded conflicting results.

Seventy patients with STEMI successfully treated with primary percutaneous coronary intervention within 12 h from symptom onset underwent CMR 3 ± 2 days after hospital admission. Patients were subcategorized into 4 time-to-reperfusion (symptom onset to balloon) quartiles: ≤90 min (group I, n = 19), >90 to 150 min (group II, n = 17), >150 to 360 min (group III, n = 17), and >360 min (group IV, n = 17). T2-weighted short tau inversion recovery and late gadolinium enhancement CMR were used to characterize reversible and irreversible myocardial injury (area at risk and IS, respectively); salvaged myocardium was defined as the normalized difference between extent of T2-weighted short tau inversion recovery and late gadolinium enhancement.

Shorter time-to-reperfusion (group I) was associated with smaller IS and microvascular obstruction and larger salvaged myocardium. Mean IS progressively increased overtime: 8% (group I), 11.7% (group II), 12.7% (group III), and 17.9% (group IV), p = 0.017; similarly, MVO was larger in patients reperfused later (0.5%, 1.5%, 3.7%, and 6.6%, respectively, p = 0.047). Accordingly, salvaged myocardium markedly decreased when reperfusion occurred >90 min of coronary occlusion (8.5%, 3.2%, 2.4%, and 2.1%, respectively, p = 0.004).

In patients with STEMI treated with primary percutaneous coronary intervention, time to reperfusion determines the extent of reversible and irreversible myocardial injury assessed by CMR. In particular, salvaged myocardium is markedly reduced when reperfusion occurs >90 min of coronary occlusion.

Periprocedural MI is a prognostically important complication of PCI.

The day before the elective PCI, 668 statin-naive patients were randomly assigned to atorvastatin 80 mg (atorvastatin group; n = 338) or no statin treatment (control group; n = 330). Creatine kinase-myocardial isoenzyme (CK-MB) (upper limit of normal [ULN] 3.5 ng/ml) and cardiac troponin I (ULN 0.10 ng/ml) were assessed before and 6 and 12 h after the intervention. Periprocedural MI was defined as a CK-MB elevation >3x ULN alone or associated with chest pain or ST-segment or T-wave abnormalities.

The incidence of a periprocedural MI was 9.5% in the atorvastatin group and 15.8% in the control group (odds ratio: 0.56; 95% confidence interval: 0.35 to 0.89; p = 0.014). Median CK-MB peak after PCI was 2.10 ng/ml (interquartile range 1.00 to 12.50 ng/ml) in the atorvastatin group and 3.20 ng/ml (interquartile range 1.37 to 16.07 ng/ml) in the control group (p = 0.014). The incidence of cardiac troponin I elevation >3x ULN was 26.6% in the atorvastatin group and 39.1% in the control group (odds ratio: 0.56; 95% confidence interval: 0.40 to 0.78; p < 0.001).

A single, high (80 mg) loading (within 24 h) dose of atorvastatin reduces the incidence of periprocedural MI in elective PCI.

Epicardial coronary thrombosis often causes microemboli and microvascular obstruction. The consequences of myocardial microvessel obstruction and myocyte necrosis are substantial, yet histopathologic characterization of epicardial coronary artery plaque has been incompletely characterized. This study examined myocardial microvascular emboli, and related these to plaque in the coronary arteries supplying the microvessels.

Hearts from sudden coronary death patients underwent examination for coronary artery plaque type and cardiac microemboli.

Forty-four hearts were available for evaluation. Mean age at death was 51 ± 15 years. Coronary artery analysis found 26 plaque ruptures and 21 erosions, and a mean of 4.5 microemboli per heart. Microemboli and microvascular obstruction occurred most often from eroded plaques. Microemboli and occluded intramyocardial vessels were most common in the left anterior descending coronary artery, and all vessels contained fibrin and platelets. Mean stenoses of the culprit lesion was 74% in those with emboli and 75% in those without (p = NS). Intramyocardial microemboli were more common in plaque erosion than in rupture. Microvessels <200 µm were most often those that were occluded.

Microemboli and microvascular obstruction are common in patients dying of acute coronary thrombosis. Plaque erosion is more likely to cause emboli in vessels <200 µm. These emboli and microvessel obstruction have a prominent clinical role since myonecrosis is often associated with these findings.

The prediction of SCD remains an important challenge in patients with mild-to-moderate chronic HF. Concentrations of sST2 have been found increased and related to worse long-term outcomes in patients with acute HF. Whether sST2 has a prognostic role in SCD is unknown.

A nested case-control study was performed on 36 cases of SCD and 63 control patients (matched for age, sex, and left ventricular ejection fraction) obtained from the MUSIC (MUerte Súbita en Insuficiencia Cardíaca) registry, a 3-year multicenter registry of ambulatory HF patients (New York Heart Association functional class II to III, left ventricular ejection fraction ≤45%). Demographic, clinical, echocardiographic, electrical, and biochemical data were collected at enrollment.

Concentrations of sST2 were greater among decedents (0.23 ng/ml [interquartile range 0.16 to 0.43 ng/ml] vs. 0.12 ng/ml [interquartile range 0.06 to 0.23 ng/ml], p = 0.001) and were predictive of experiencing SCD (+0.1 ng/ml, odds ratio: 1.39, 95% confidence interval: 1.09 to 1.78, p = 0.006). On the basis of a combined biomarker status, only 4% of patients experienced SCD for neither sST2 nor N-terminal pro–B-type natriuretic peptide (NT-proBNP) above receiver-operator characteristic-derived cut-off points (0.15 ng/ml and 2,000 ng/l, respectively), 34% for either biomarker above, and 71% for both biomarkers above (p < 0.001 for trend). This combined variable added incremental prognostic value to the multivariable regression model (p < 0.001).

Elevated sST2 concentrations are predictive of SCD in patients with chronic HF and provide complementary information to NT-proBNP levels. A combined biomarker approach may have an impact on clinical decision-making.

Arterial duct stenting is increasingly deemed a reliable alternative to surgical shunt in CHD-DPC. A stented duct might better adapt to the PA anatomy than a surgical conduit, thereby promoting a more uniform PA development.

This study enrolled 27 patients with CHD-DPC submitted to AD stenting (n = 13, Group I) or MBTS (n = 14, Group II) at our institution. The PA growth was angiographically assessed with the Nakata and McGoon indexes as well as the individual PA z-scores. The right-to-left PA diameter ratio was considered as index of uniform growth.

After 10 ± 5 months, both options had promoted a significant increase of the Nakata index (from 136 ± 72 mm/m² to 294 ± 99 mm/m², p < 0.0001, Group I; from 151 ± 74 mm/m² to 295 ± 177 mm/m², p < 0.003, Group II) and McGoon ratio (from 1.5 ± 0.3 to 2.1 ± 0.3, p < 0.0001, Group I; from 1.6 ± 0.3 to 2.0 ± 0.5, p < 0.01, Group II). However, the surgical shunt had caused a worsening of the left-to-right PA diameter ratio compared with AD stenting (0.9 ± 0.1 Group I vs. 1.6 ± 0.9 Group II, p < 0.01), due to preferential growth of the PA contralateral to the shunt.

Percutaneous AD stenting is as effective as MBTS in promoting a global PA growth in CHD-DPC. In addition, it ensures an even distribution of the pulmonary blood flow, thereby promoting a more balanced pulmonary vascular development than MBTS.

Binge drinking may exert cardiac toxicity and interfere with heart function, manifested as impaired ventricular contractility, although the underlying mechanism remains poorly defined.

ALDH2 transgenic mice were produced using the chicken beta-actin promoter. Wild-type FVB (friend virus B) and ALDH2 mice were challenged with ethanol (3 g/kg, intraperitoneally), and cardiac function was assessed 24 h later using the Langendroff and cardiomyocyte edge-detection systems. Western blot analysis was used to evaluate protein phosphatase 2A and 2C (PP2A and PP2C), phosphorylation of Akt, AMP-activated protein kinase (AMPK), and the transcription factors Foxo3 (Thr32 and Ser413).

ALDH2 reduced ethanol-induced elevation in cardiac acetaldehyde levels. Acute ethanol challenge deteriorated myocardial and cardiomyocyte contractile function evidenced by reduction in maximal velocity of pressure development and decline (±dP/dt), left ventricular developed pressure, cell shortening, and prolonged relengthening duration, the effects of which were alleviated by ALDH2. Ethanol treatment dampened phosphorylation of Akt and AMPK associated with up-regulated PP2A and PP2C, which was abrogated by ALDH2. ALDH2 significantly attenuated ethanol-induced decrease in Akt- and AMPK-stimulated phosphorylation of Foxo3 at Thr32 and Ser413, respectively. Consistently, ALDH2 rescued ethanol-induced myocardial apoptosis, protein damage, and mitochondrial membrane potential depolarization.

Our results suggest that ALDH2 is cardioprotective against acute ethanol toxicity, possibly through inhibition of protein phosphatases, leading to enhanced Akt and AMPK activation, and subsequently, inhibition of Foxo3, apoptosis, and mitochondrial dysfunction.

There are significant sex-based differences in prevalence and manifestation of SCA. Any differences related to predictors of SCA in women versus men are likely to have implications for risk stratification and prevention.

The Ore-SUDS (Oregon Sudden Unexpected Death Study) is an ongoing prospective investigation of SCA in the Portland, Oregon, metropolitan area (population approximately 1 million). All cases meeting criteria for SCA were ascertained using multiple sources. Medical records were reviewed to identify clinical conditions that may contribute to SCA risk, and comparisons were made between male and female SCA cases using Pearson's chi-square tests for categorical variables, t tests for continuous variables, and multivariate logistic regression analysis.

During 2002 to 2007, 1,568 adult SCA cases were identified (women 36% vs. men 64%; p < 0.0001) and women were older (mean age 71 ± 14 years vs. 65 ± 14 years, p < 0.0001). There were no significant sex differences in prevalence of obesity, dyslipidemia, history of chronic obstructive pulmonary disease/asthma, left ventricular (LV) hypertrophy, or history of myocardial infarction. In multivariate analysis, women were significantly less likely to have severe LV dysfunction (odds ratio: 0.51; 95% confidence interval: 0.31 to 0.84) or previously recognized coronary artery disease (odds ratio: 0.34; 95% confidence interval: 0.20 to 0.60) compared with men.

Women were significantly less likely than men to have a diagnosis of structural heart disease (LV dysfunction or coronary artery disease) before SCA. These findings suggest that fewer women may be eligible for prophylactic implantable cardioverter-defibrillator placement based on current guidelines and therefore may not have equal opportunity for prevention. Enhancement of SCA risk stratification may have even higher importance for women.

Pacemaker patient follow-up procedures have evolved from evaluating devices with little programmability and diagnostic information solely in person to transtelephonic rhythm strip recordings that allow monitoring of basic device function. More recently developed remote monitoring technology leverages expanded device capabilities, augmenting traditional transtelephonic monitoring to evaluate patients via full device interrogation.

The time to first diagnosis of a clinically actionable event was compared in patients who were followed by remote interrogation (Remote) and those who were followed per standard of care with office visits augmented by transtelephonic monitoring (Control). Patients were randomized 2:1. Remote arm patients transmitted pacemaker information at 3-month intervals. Control arm patients with a single-chamber pacemaker transmitted at 2-month intervals. Control arm patients with dual-chamber devices transmitted at 2-month intervals with an office visit at 6 months. All patients were seen in office at 12 months.

The mean time to first diagnosis of clinically actionable events was earlier in the Remote arm (5.7 months) than in the Control arm (7.7 months). Three (2%) of the 190 events in the Control arm and 446 (66%) of 676 events in the Remote arm were identified remotely.

The strategic use of remote pacemaker interrogation follow-up detects actionable events that are potentially important more quickly and more frequently than transtelephonic rhythm strip recordings. The use of transtelephonic rhythm strips for pacemaker follow-up is of little value except for battery status determinations. (PREFER [Pacemaker Remote Follow-up Evaluation and Review]; NCT00294645)

Limited information is available on whether atrial fibrillation incidence is affected differentially by different classes of antihypertensive medications or treatment with statins.

AF/AFL was identified from baseline and follow-up electrocardiograms performed biannually. Analyses were performed to identify characteristics associated with baseline AF/AFL and its subsequent incidence.

AF/AFL was present at baseline in 423 participants (1.1%), more frequent in men (odds ratio: 1.72; 95% confidence interval [CI]: 1.37 to 2.17) and nonblacks (odds ratio: 2.09; 95% CI: 1.58 to 2.75). Its prevalence increased with age (p < 0.001) and was associated with CHD, cardiovascular disease, obesity, and high-density lipoprotein cholesterol <35 mg/dl. New-onset AF/AFL was associated with the same baseline risk factors plus electrocardiogram left ventricular hypertrophy. It occurred in 641 participants (2.0%) and, excluding doxazosin, did not differ by antihypertensive treatment group or, in a subset of participants, by pravastatin versus usual care. Baseline AF/AFL was associated with increased mortality (hazard ratio [HR]: 2.82; 95% CI: 2.36 to 3.37; p < 0.001), stroke (HR: 3.63; 95% CI: 2.72 to 4.86; p < 0.001), heart failure (HR: 3.17; 95% CI: 2.38 to 4.25; p < 0.001), and fatal CHD or nonfatal myocardial infarction (HR: 1.64; 95% CI: 1.22 to 2.21; p < 0.01). There was a nearly 2.5-fold increase in mortality risk when AF/AFL was present at baseline or developed during the trial (HR: 2.42; 95% CI: 2.11 to 2.77; p < 0.001).

In this high-risk hypertensive population, pre-existing and new-onset AF/AFL were associated with increased mortality. Excluding doxazosin, treatment assignment to either antihypertensive drugs or pravastatin versus usual care did not affect AF/AFL incidence. (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial [ALLHAT]; NCT00000542)

There is no clear consensus of whether a screening TEE before catheter ablation of AF should be performed in every patient.

Initial TEEs for pre-PVI of 1,058 AF patients (age 57 ± 11 years, 80% men) were reviewed and compared with a CHADS₂ score.

CHADS₂ scores of 0, 1, 2, 3, 4, 5, and 6 were present in 47%, 33%, 14%, 5%, 1%, 0.3%, and 0% of patients, respectively. The prevalence of LA/LAA thrombus, sludge, and spontaneous echo contrast were present in 0.6%, 1.5%, and 35%. The prevalence of LA/LAA thrombus/sludge increased with ascending CHADS₂ score (scores 0 [0%], 1 [2%], 2 [5%], 3 [9%], and 4 to 6 [11%], p < 0.01). No patient with a CHADS₂ score of 0 had LA/LAA sludge/thrombus. In a multivariate model, history of congestive heart failure and left ventricular ejection fraction <35% were significantly associated with sludge/thrombus.

The prevalence of LA/LAA sludge/thrombus in patients with AF undergoing a pre-PVI screening TEE is very low (<2%) and increases significantly with higher CHADS₂ scores. This suggests that a screening TEE before PVI should be performed in patients with a CHADS₂ score of ≥1, and in patients with a CHADS₂ score of 0 when the AF is persistent and therapeutic anticoagulation has not been maintained for 4 weeks before the procedure.

Atrial fibrillation is a common complication after thoracic surgery. Pulmonary vein isolation is an effective treatment for AF. Heart or double-lung transplantation surgery both involve pulmonary vein isolation because of suture lines.

We reviewed the records of 174 consecutive heart transplant patients and 122 double-lung transplant patients at the Columbia Presbyterian Medical Center between January 2005 and June 2008. Electrocardiograms during atrial arrhythmia episodes were reviewed by an electrophysiologist. Clinical variables, biopsy results, immunosuppressive regimens, and echocardiographic measurements were collected from the perioperative time period and at the time of arrhythmia occurrence.

In the heart transplant group, 8 (4.6%) patients had AF (group A). In the lung transplant group, 23 (18.9%) patients had AF (group B; p < 0.001). The incidence of AF in a comparison group of 131 patients with normal left ventricular function who underwent coronary artery bypass graft surgery was 19.8%. Immunosuppressive regimens and clinical variables were similar for both groups. Echocardiographic data revealed no significant cardiac abnormalities in 74% of group B compared with 25% of group A (p < 0.05), and 78% of biopsy results in group B were normal, whereas only 25% of group A results were normal (p < 0.05).

In heart transplant recipients, AF is uncommon and occurs in the setting of myocardial dysfunction and graft rejection. In contrast, AF is more common after lung transplantation despite the absence of graft rejection and cardiac dysfunction. Pulmonary vein isolation alone cannot explain the discrepancy in AF incidence between heart transplant recipients and double-lung transplant recipients. Cardiac autonomic denervation may have a protective effect for heart transplant patients in the post-operative setting.

Previous studies were limited by population size in their ability to examine phenotypic effect of location, type, and topology.

Study subjects included 858 type 2 LQTS patients with 162 different KCNH2 mutations in 213 proband-identified families. The Cox proportional-hazards survivorship model was used to evaluate independent contributions of clinical and genetic factors to the first cardiac events.

For patients with missense mutations, the transmembrane pore (S5-loop-S6) and N-terminus regions were a significantly greater risk than the C-terminus region (hazard ratio [HR]: 2.87 and 1.86, respectively), but the transmembrane nonpore (S1–S4) region was not (HR: 1.19). Additionally, the transmembrane pore region was significantly riskier than the N-terminus or transmembrane nonpore regions (HR: 1.54 and 2.42, respectively). However, for nonmissense mutations, these other regions were no longer riskier than the C-terminus (HR: 1.13, 0.77, and 0.46, respectively). Likewise, subjects with nonmissense mutations were at significantly higher risk than were subjects with missense mutations in the C-terminus region (HR: 2.00), but that was not the case in other regions. This mutation location–type interaction was significant (p = 0.008). A significantly higher risk was found in subjects with mutations located in -helical domains than in subjects with mutations in β-sheet domains or other locations (HR: 1.74 and 1.33, respectively). Time-dependent β-blocker use was associated with a significant 63% reduction in the risk of first cardiac events (p < 0.001).

The KCNH2 missense mutations located in the transmembrane S5-loop-S6 region are associated with the greatest risk.

Mutations in RYR2 cause type 1 catecholaminergic polymorphic ventricular tachycardia (CPVT1), a cardiac channelopathy with increased propensity for lethal ventricular dysrhythmias. Most RYR2 mutational analyses target 3 canonical domains encoded by <40% of the translated exons. The extent of CPVT1-associated mutations localizing outside of these domains remains unknown as RYR2 has not been examined comprehensively in most patient cohorts.

Mutational analysis of all RYR2 exons was performed using polymerase chain reaction, high-performance liquid chromatography, and deoxyribonucleic acid sequencing on 155 unrelated patients (49% females, 96% Caucasian, age at diagnosis 20 ± 15 years, mean QTc 428 ± 29 ms), with either clinical diagnosis of CPVT (n = 110) or an initial diagnosis of exercise-induced long QT syndrome but with QTc <480 ms and a subsequent negative long QT syndrome genetic test (n = 45).

Sixty-three (34 novel) possible CPVT1-associated mutations, absent in 400 reference alleles, were detected in 73 unrelated patients (47%). Thirteen new mutation-containing exons were identified. Two-thirds of the CPVT1-positive patients had mutations that localized to 1 of 16 exons.

Possible CPVT1 mutations in RYR2 were identified in nearly one-half of this cohort; 45 of the 105 translated exons are now known to host possible mutations. Considering that 65% of CPVT1-positive cases would be discovered by selective analysis of 16 exons, a tiered targeting strategy for CPVT genetic testing should be considered.

An increasing number of clinical reports have associated sleep apnea and AF, and many possible mechanisms responsible for this relationship have been proposed.

Thirty dogs anesthetized with Na-pentobarbital were ventilated by a positive pressure respirator. Protocol 1 (n = 14): After a right thoracotomy, atrial and pulmonary vein programmed pacing at 2x and 4x threshold determined the shortest atrial refractory period. Obstructive apnea was induced by turning off the respirator during end expiration for 2 min. During apnea, programmed pacing was performed with S1-S2 = 5 to 10 ms earlier than the atrial refractory period. Neural activity was monitored from the ganglionated plexi (GP) adjacent to the right pulmonary veins. Protocol 2 (n = 16): Electrical stimulation identified the GP at the right pulmonary artery (RPA). Programmed pacing was again instituted, below atrial refractory period, during 2 min of apnea. After radiofrequency ablation of the RPA GP, continuous programmed pacing was again repeated during 2 min of apnea. In 5 dogs, blood gases were determined at baseline and at 2 min of apnea.

Protocol 1: During apnea, S1-S2 induced AF within 85 ± 38 s (9 of 10). In 1 case, AF occurred spontaneously at 1 min 36 s of apnea. Recorded GP neural activity progressively increased before AF onset. Systolic but not diastolic blood pressure rose significantly before AF (149 ± 26 mm Hg to 193 ± 38 mm Hg, p < 0.05). In 4 dogs, autonomic blockade prevented apnea-induced AF. Protocol 2: AF induced by pacing occurred in 8 of 11 dogs within the 2-min period of apnea, before neural ablation. After ablation, 0 of 6 showed AF during 2 min of apnea (p = 0.009).

This experimental model of apnea shows a reproducible incidence of AF. After neural ablation of the RPA GP or autonomic blockade, AF inducibility was significantly inhibited.

Consensus documents attribute the aging changes in BP to wave reflection moving progressively from diastole into systole. However, the extensive quantitative data on this phenomenon have never been systematically reviewed. Individual studies have been small, and limited to a narrow age range.

Using PubMed, Cochrane, and Web of Science databases, we identified 64 studies (including 13,770 subjects, age range 4 to 91 years) reporting the timing of wave reflection, defined as the time from the onset (foot) of the pressure waveform to the shoulder point (anachrotic notch).

In subjects of all ages, reflection times were well within systole. There was a small tendency for younger subjects to have later reflection, but this was only 0.7 ms per year, whereas the weighted mean reflection time was 136 ms (99% confidence interval: 130 to 141 ms) and the mean duration of systole was 328 ms (99% confidence interval: 310 to 347 ms). At this rate of change with age, arrival of wave reflection would only be construed to be in diastole at an extrapolated age of –221 years.

These findings challenge the current consensus view that a shift in timing of wave reflection significantly contributes to the changes in the BP waveform with aging. We should re-evaluate the mechanisms of BP elevation in aging.

Anemia is common in acquired heart failure and affects prognosis. The presence of anemia and its relation to outcome in ACHD remain unknown.

Data were collected on consecutive noncyanotic ACHD patients attending our tertiary center between 2001 and 2006 in whom hemoglobin concentration was measured. Anemia was defined as hemoglobin concentration <13 g/dl in males and <12 g/dl in females. Cyanotic patients were excluded to avoid confounding from secondary erythrocytosis.

Overall, 830 noncyanotic ACHD patients (age 36.5 ± 15.0 years, 49.6% male) fulfilled the inclusion criteria. The prevalence of anemia was 13.1% and was highest in patients with congenitally corrected transposition of great arteries and Ebstein anomaly of the tricuspid valve. Anemic patients were more likely to be receiving diuretics (p < 0.0001) and have a lower mean corpuscular volume (p = 0.0001), with a trend toward a higher New York Heart Association functional class (p = 0.06). During a median follow-up of 47 months, 55 patients died. Anemic patients had a 3-fold higher mortality risk compared with nonanemic patients, even after propensity score adjustment for clinical variables such as systemic ventricular function, renal impairment, and diuretic therapy (adjusted hazard ratio: 3.00; 95% confidence interval: 1.46 to 6.13).

Anemia is not uncommon in ACHD patients attending tertiary services and is associated with a 3-fold increased risk of death. Screening for anemia should be part of the routine assessment of ACHD patients for risk stratification and treatment when correctable causes are identified.

Clinically, stent fracture has been reported in 1% to 2% of patients after drug-eluting stent (DES) implantation.

High-contrast film-based radiographs of 177 consecutive lesions from the CVPath DES autopsy registry were reviewed. Stent fracture was graded as I (single-strut fracture), II (≥2 struts), III (≥2 struts with deformation), IV (with transection without gap), and V (with transection causing gap in stent segment). The incidence of adverse pathologic findings (thrombosis and restenosis) was assessed histologically.

Stent fracture was documented in 51 lesions (29%; grade I = 10, II = 14, III = 12, IV = 6, and V = 9). Lesions with stent fracture had longer duration after implantation (172 days [interquartile range (IQR) 31 to 630 days] vs. 44 days [IQR 7 to 270 days], p = 0.004), a higher rate of Cypher (Cordis Corp., Miami Lakes, Florida) stent usage (63% vs. 36%, p = 0.001), longer stent length (30.0 mm [IQR 22.0 to 40.0 mm] vs. 20.0 mm [IQR 14.0 to 27.3 mm], p < 0.0001), and a higher rate of overlapping stents (45% vs. 22%, p = 0.003). Although fracture with grade I to IV did not have significant impact on the occurrence of adverse pathologic findings such as thrombosis and restenosis, 67% of the grade V fracture lesions were associated with adverse pathologic findings at fracture sites. Longer stent length, use of Cypher, and longer duration of implant were identified as independent risk factors of stent fracture by logistic regression analysis.

The incidence of stent fracture was 29% lesions at autopsy, which is much higher than clinically reported. A high rate of adverse pathologic findings was observed in lesions with grade V stent fracture, whereas fracture with grade I to IV did not have a significant impact on the pathological outcome.

Previous analyses have shown sex-based differences in response to several antiplatelet medications. Little is known about the efficacy and safety of clopidogrel in women and men.

This study performed a meta-analysis of all blinded randomized clinical trials comparing clopidogrel and placebo (CURE [Clopidogrel in Unstable Angina to Prevent Recurrent Events], CREDO [Clopidogrel for the Reduction of Events During Observation], CLARITY–TIMI 28 [Clopidogrel as Adjunctive Reperfusion Therapy–Thrombolysis In Myocardial Infarction 28], COMMIT [Clopidogrel and Metoprolol in Myocardial Infarction Trial], and CHARISMA [Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance] trials), involving a total of 79,613 patients, of whom 30% were women. The relative efficacy and safety of clopidogrel at reducing cardiovascular events (cardiovascular death, myocardial infarction [MI], or stroke) in women and men was estimated using random-effects modeling.

Overall, clopidogrel was associated with a highly significant 14% proportional reduction in the risk of cardiovascular events (odds ratio [OR]: 0.86; 95% confidence interval [CI]: 0.80 to 0.93), with no significant differences in treatment effect between women and men. Among the 23,533 women enrolled, there were fewer cardiovascular events in the clopidogrel group compared with the placebo group (11.0% vs. 11.8%; OR: 0.93; 95% CI: 0.86 to 1.01). In women the risk reduction with clopidogrel seemed to be greatest for MI (OR: 0.81; 95% CI: 0.70 to 0.93), with the effects on stroke (OR: 0.91; 95% CI: 0.69 to 1.21) or total death (OR: 0.99; 95% CI: 0.90 to 1.08) not statistically significant. Among the 56,091 men enrolled, there were fewer cardiovascular events in those receiving clopidogrel compared with placebo (7.8% vs. 9.0%; OR: 0.84; 95% CI: 0.78 to 0.91), and the risk reduction was significant for MI (OR: 0.83; 95% CI: 0.76 to 0.92), stroke (OR: 0.83; 95% CI: 0.71 to 0.96), and total death (OR: 0.91; 95% CI: 0.84 to 0.97). Clopidogrel increased the risk of major bleeding in both women (OR: 1.43; 95% CI: 1.15 to 1.79) and men (OR: 1.22; 95% CI: 1.05 to 1.42).

Clopidogrel reduces the risk of cardiovascular events in both women and men.

SF defined by catheter angiography or intravascular ultrasound has been implicated in ISR.

A total of 292 consecutive patients, with 613 stents, who underwent CTA were evaluated for stent gaps associated with decreased Hounsfield units. Correlations with catheter coronary angiography (CCA) were available in 143 patients with 384 stents.

Stent gaps were noted in 16.9% by CTA and 1.0% by CCA. ISR by CCA was noted in 46.1% of the stent gaps (p < 0.001) as determined by CCA, and stent gaps by CTA accounted for 27.8% of the total ISR (p < 0.001). In univariate analysis, stent diameter ≥3 mm was the only CCA characteristic significantly associated with stent gaps (p = 0.002), but was not a significant predictor by multivariate analysis. Bifurcation stents, underlying calcification, stent type, location, post-dilation, and overlapping stents were not observed to be predisposing factors. Excessive tortuosity and lack of conformability were not associated with stent gaps; however, their frequency was insufficient to permit meaningful analysis.

Stent gap by CTA: 1) is associated with 28% of ISR, and ISR is found in 46% of stent gaps; 2) is associated with ≥3-mm stents by univariate (p = 0.002) but not by multivariate analysis; 3) is infrequently noted on catheter angiography; and 4) most likely represents SF in the setting of a single stent, and may represent SF or OF in overlapping stents.

LVESD is a marker of left ventricular function in patients with organic MR but its association to survival after diagnosis is unknown.

The MIDA (Mitral Regurgitation International Database) registry is a multicenter registry of echocardiographically diagnosed organic MR due to flail leaflets. We enrolled 739 patients with MR due to flail leaflets (age 65 ± 12 years; ejection fraction: 65 ± 10%) in whom LVESD was measured (36 ± 7 mm).

Under conservative management, 10-year survival and survival free of cardiac death were higher with LVESD <40 mm versus ≥40 mm (64 ± 5% vs. 48 ± 10%; p < 0.001, and 73 ± 5% vs. 63 ± 10%; p = 0.001). LVESD ≥40 mm independently predicted overall mortality (hazard ratio [HR]: 1.95, 95% confidence interval [CI]: 1.01 to 3.83) and cardiac mortality (HR: 3.09, 95% CI: 1.35 to 7.09) under conservative management. Mortality risk increased linearly with LVESD >40 mm (HR: 1.15, 95% CI: 1.04 to 1.27 per 1-mm increment). During the entire follow-up (including post-surgical), LVESD ≥40 mm independently predicted overall mortality (HR: 1.86, 95% CI: 1.24 to 2.80) and cardiac mortality (HR: 2.14, 95% CI: 1.29 to 3.56), due to persistence of excess mortality in patients with LVESD ≥40 mm after surgery (HR: 1.86, 95% CI: 1.11 to 3.15 for overall death, and HR: 1.81, 95% CI: 1.05 to 3.54 for cardiac death).

In MR due to flail leaflets, LVESD ≥40 mm is independently associated with increased mortality under medical management but also after mitral surgery. These findings support prompt surgical rescue in patients with LVESD ≥40 mm but also suggest that best preservation of survival is achieved in patients operated before LVESD reaches 40 mm.

Ambrisentan is an oral, once-daily endothelin receptor antagonist that is selective for the endothelin type A receptor. The ARIES-1 (Ambrisentan in Pulmonary Arterial Hypertension, Randomized, Double-Blind, Placebo-Controlled, Multicenter, Efficacy Studies) and ARIES-2 trials were the pivotal 12-week, placebo-controlled studies that led to the regulatory approval of ambrisentan (5 and 10 mg) for the treatment of PAH.

In the ARIES-1 and -2 studies, and the subsequent long-term extension protocol, the ARIES-E study, 383 patients received ambrisentan (2.5, 5, or 10 mg). Efficacy and safety assessments are presented from the time of the first dose of ambrisentan for all patients with post-baseline data.

After 2 years of ambrisentan exposure, the mean change from baseline in 6-min walk distance was improved for the 5-mg (+23 m; 95% confidence interval: 9 to 38 m) and 10-mg (+28 m; 95% confidence interval: 11 to 45 m) groups. Estimates of survival and freedom from clinical worsening for the combined dose group were 94% and 83%, respectively, at 1 year and 88% and 72%, respectively, at 2 years. The annualized risk of aminotransferase abnormalities >3x the upper limit of normal was ~2% per year; most of these events were mild and did not lead to discontinuation of drug.

Two years of ambrisentan treatment was associated with sustained improvements in exercise capacity and a low risk of clinical worsening and death in patients with PAH. Ambrisentan was generally well tolerated and had a low risk of aminotransferase abnormalities over the 2-year study period. (A Long Term Study of Ambrisentan in Pulmonary Arterial Hypertension Subjects Having Completed AMB-320 or AMB-321; NCT00578786)

Although left atrial enlargement (LAE) is an independent risk factor for atrial fibrillation, stroke, and death, little information is available about determinants of LA size in the general population.

Participants (1,212 men and women, age 25 to 74 years) originated from a sex- and age-stratified random sample of German residents of the Augsburg area (MONICA S3). Left atrial volume was determined by standardized echocardiography at baseline and again after 10 years. Left atrial volume was indexed to body height (iLA). Left atrial enlargement was defined as iLA ≥35.7 and ≥33.7 ml/m in men and women, respectively.

At baseline, the prevalence of LAE was 9.8%. Both obesity and hypertension were independent predictors of LAE, obesity (odds ratio [OR]: 2.4; p < 0.001) being numerically stronger than hypertension (OR: 2.2; p < 0.001). Adjusted mean values for iLA were significantly lower in normal-weight hypertensive patients (25.4 ml/m) than in obese normotensive individuals (27.3 ml/m; p = 0.016). The highest iLA was found in the obese hypertensive subgroup (30.0 ml/m; p < 0.001 vs. all other groups). This group also presented with the highest increase in iLA (+6.0 ml/m) and the highest incidence (31.6%) of LAE upon follow-up.

In the general population, obesity appears to be the most important risk factor for LAE. Given the increasing prevalence of obesity, early interventions, especially in young obese individuals, are essential to prevent premature onset of cardiac remodeling at the atrial level.

Previous data suggest that CRT slows disease progression and improves the outcomes of asymptomatic or mildly symptomatic patients with left ventricular (LV) dysfunction and a wide QRS complex.

We randomly assigned 262 recipients of CRT pacemakers or defibrillators, with QRS ≥120 ms and LV ejection fraction ≤40% to active (CRT ON; n = 180) versus control (CRT OFF; n = 82) treatment, for 24 months. Mean baseline LV ejection fraction was 28.0%. All patients were in sinus rhythm and receiving optimal medical therapy. The primary study end point was the proportion worsened by the heart failure (HF) clinical composite response. The main secondary study end point was left ventricular end-systolic volume index (LVESVi).

In the CRT ON group, 19% of patients were worsened versus 34% in the CRT OFF group (p = 0.01). The LVESVi decreased by a mean of 27.5 ± 31.8 ml/m² in the CRT ON group versus 2.7 ± 25.8 ml/m² in the CRT OFF group (p < 0.0001). Time to first HF hospital stay or death (hazard ratio: 0.38; p = 0.003) was significantly delayed by CRT.

After 24 months of CRT, and compared with those of control subjects, clinical outcomes and LV function were improved and LV dimensions were decreased in this patient population in New York Heart Association functional classes I or II. These observations suggest that CRT prevents the progression of disease in patients with asymptomatic or mildly symptomatic LV dysfunction. (REsynchronization reVErses Remodeling in Systolic Left vEntricular Dysfunction [REVERSE]; NCT00271154)

Statins reduce cardiovascular morbidity and mortality in many patients with ischemic heart disease but not, overall, those with heart failure. There must be a transition point at which treatment with a statin becomes futile.

In CORONA, patients with heart failure, reduced left ventricular ejection fraction, and ischemic heart disease were randomly assigned to 10 mg/day rosuvastatin or placebo. The primary composite outcome was cardiovascular death, nonfatal myocardial infarction, or stroke.

Of 5,011 patients enrolled, NT-proBNP was measured in 3,664 (73%). The midtertile included values between 103 pmol/l (868 pg/ml) and 277 pmol/l (2,348 pg/ml). Log NT-proBNP was the strongest predictor (per log unit) of every outcome assessed but was strongest for death from worsening heart failure (hazard ratio [HR]: 1.99; 95% confidence interval [CI]: 1.71 to 2.30), was weaker for sudden death (HR: 1.69; 95% CI: 1.52 to 1.88), and was weakest for atherothrombotic events (HR: 1.24; 95% CI: 1.10 to 1.40). Patients in the lowest tertile of NT-proBNP had the best prognosis and, if assigned to rosuvastatin rather than placebo, had a greater reduction in the primary end point (HR: 0.65; 95% CI: 0.47 to 0.88) than patients in the other tertiles (heterogeneity test, p = 0.0192). This reflected fewer atherothrombotic events and sudden deaths with rosuvastatin.

Patients with heart failure due to ischemic heart disease who have NT-proBNP values <103 pmol/l (868 pg/ml) may benefit from rosuvastatin.

It has not been established which is the best aortic valve substitute in patients ages 55 to 70 years. We conducted a randomized study to compare long-term outcomes between BP and MP aortic valves.

Between January 1995 and June 2003, 310 patients were randomized to receive a BP or an MP aortic valve. Primary end points of the study were survival, valve failure, and reoperation.

One hundred fifty-five patients received a BP valve, and 155 patients received an MP valve. Four patients died, perioperatively, in the MP group (2.6%), and 6 patients died in the BP group (3.9%, p = 0.4). At late follow-up (mean 106 ± 28 months) 41 patients died in the MP group and 45 patients died in the BP group (p = 0.6). There was no difference in the survival rate at 13 years between the MP and BP groups. Valve failures and reoperations were more frequent in the BP group compared with the MP group (p = 0.0001 and p = 0.0003, respectively). There were no differences in the linearized rate of thromboembolism, bleeding, endocarditis, and major adverse prosthesis-related events (MAPE) between the MP and BP valve groups.

At 13 years, patients undergoing aortic valve replacement either with MP or BP valves had a similar survival rate as well the same rate of occurrence of thromboembolism, bleeding, endocarditis, and MAPE, but patients who had undergone aortic valve replacement with BP valves faced a significantly higher risk of valve failure and reoperation.

The CACS and SPECT results both provide important prognostic information. It is unclear whether integrating these tests will better predict patient outcome.

We followed-up 1,126 generally asymptomatic subjects without previous cardiovascular disease who had a CACS and stress SPECT scan performed within a close time period (median 56 days). The median follow-up was 6.9 years. End points analyzed were total cardiac events and all-cause death/myocardial infarction (MI).

An abnormal SPECT result increased with increasing CACS from <1% (CACS ≤10) to 29% (CACS >400) (p < 0.001). Total cardiac events and death/MI also increased with increasing CACS and abnormal SPECT results (p < 0.001). In subjects with a normal SPECT result, CACS added incremental prognostic information, with a 3.55-fold relative increase for any cardiac event (2.75-fold for death/MI) when the CACS was severe (>400) versus minimal (≤10). Separation of the survival curves occurred at 3 years after initial testing for all cardiac events and at 5 years for death/MI.

The CACS and SPECT findings are independent and complementary predictors of short- and long-term cardiac events. Despite a normal SPECT result, a severe CACS identifies subjects at high long-term cardiac risk. After a normal SPECT result, our findings support performing a CACS in patients who are at intermediate or high clinical risk for coronary artery disease to better define those who will have a high long-term risk for adverse cardiac events.

Little is known about PT histology in patients with tetralogy of Fallot (TOF), especially in the era of surgical intervention in childhood.

We studied 39 formalin-fixed necropsy heart specimens with TOF and compared them with 17 normal control heart specimens. Sections of the PT and aorta were studied by light microscopy using various stains; histological findings were graded according to severity.

Among the TOF group (1 fetus, 11 infants, 14 children, and 13 adults), 11 patients had undergone palliative and 10 patients had undergone reparative surgery at a median age of 8 years (range 2.5 to 18 years). Histological changes of grade 2 or higher were present in 59% (medionecrosis), 36% (fibrosis), 56% (cystlike formation), and 56% (abnormal elastic tissue configuration) of TOF patients. Total histology grading scores were higher in TOF hearts (median 6, range 1 to 9) compared with controls (median 1, range 0 to 6; p < 0.0001). Histological abnormalities were present among infants (median score 3.5, range 1 to 9) and after palliative surgery (median score 5, range 2 to 9) or repair (median score 7.5, range 4 to 9).

Marked histological abnormalities in the PT of hearts with TOF exist compared with controls. These changes were present from infancy and among patients who had undergone palliative or reparative surgery, although operations in this cohort were performed late. Our data suggest that structural abnormalities of the PT, similar to these recently shown in the aorta, are intrinsic.

Heart failure represents a major cause of death among diabetic patients. It has been proposed that derangements in cardiac metabolism and oxidative stress may underlie the progression of this comorbidity, but scarce evidence exists in support of this mechanism in humans.

Mitochondrial oxygen (O₂) consumption and hydrogen peroxide (H₂O₂) emission were measured in permeabilized myofibers prepared from samples of the right atrial appendage obtained from nondiabetic (n = 13) and diabetic (n = 11) patients undergoing nonemergent coronary artery bypass graft surgery.

Mitochondria in atrial tissue of type 2 diabetic individuals show a sharply decreased capacity for glutamate and fatty acid-supported respiration, in addition to an increased content of myocardial triglycerides, as compared to nondiabetic patients. Furthermore, diabetic patients show an increased mitochondrial H₂O₂ emission during oxidation of carbohydrate- and lipid-based substrates, depleted glutathione, and evidence of persistent oxidative stress in their atrial tissue.

These findings are the first to directly investigate the effects of type 2 diabetes on a panoply of mitochondrial functions in the human myocardium using cellular and molecular approaches, and they show that mitochondria in diabetic human hearts have specific impairments in maximal capacity to oxidize fatty acids and glutamate, yet increased mitochondrial H₂O₂ emission, providing insight into the role of mitochondrial dysfunction and oxidative stress in the pathogenesis of heart failure in diabetic patients.