American Journal of Cardiology

Eugene Braunwald, MD and the Early Years of Hypertrophic Cardiomyopathy: A Conversation With Dr. Barry J. Maron

Barry J. Maron, Eugene Braunwald — 2012-03-19

There is some uncertainty, and even controversy, as to when hypertrophic cardiomyopathy was first recognized. Dating back to 1868, there are autopsy-based case reports from France, Germany, and the United Kingdom composed of 1 or a few patients who appear to have died suddenly of a disease consistent in its features with hypertrophic cardiomyopathy. The 1959 and 1960 reports from London of Brock (clinical) and Teare (pathologic) are generally regarded as the first contemporary descriptions of hypertrophic cardiomyopathy. However, it is appropriate at this time to reflect on how and why this important disease was transformed from the subject of a few anecdotal case reports into a robust and treatable clinical entity ultimately regarded as a common genetic heart disease and the most frequent cause of sudden death in young individuals (including trained athletes).

Influence of Diabetes Mellitus on Long-Term (Five-Year) Outcomes of Drug-Eluting Stents and Coronary Artery Bypass Grafting for Multivessel Coronary Revascularization

2012-03-19

Diabetes mellitus is a major risk factor for coronary artery disease (CAD) and for diffuse and progressive atherosclerosis. We evaluated the outcomes of drug-eluting stent (DES) placement and coronary artery bypass grafting (CABG) in 891 diabetic patients (489 for DES implantation and 402 for CABG) and 2,151 nondiabetic patients (1,058 for DES implantation and 1,093 for CABG) with multivessel CAD treated from January 2003 through December 2005 and followed up for a median 5.6 years. Outcomes of interest included death; the composite outcome of death, myocardial infarction (MI), or stroke; and repeat revascularization. In diabetic patients, after adjusting for baseline covariates, 5-year risk of death (hazard ratio 1.01, 95% confidence interval 0.77 to 1.33, p = 0.96) and the composite of death, MI, or stroke (hazard ratio 1.03, 95% confidence interval 0.80 to 1.31, p = 0.91) were similar in patients undergoing DES or CABG. However, rate of repeat revascularization was significantly higher in the DES group (hazard ratio 3.69, 95% confidence interval 2.64 to 5.17, p <0.001). These trends were consistent in nondiabetic patients (hazard ratio 0.80, 95% confidence interval 0.55 to 1.16, p = 0.23 for death; hazard ratio 0.77, 95% confidence interval 0.56 to 1.05, p = 0.10 for composite of death, MI, or stroke; hazard ratio 2.77, 95% CI 1.95 to 3.91, p <0.001 for repeat revascularization). There was no significant interaction between diabetic status and treatment strategy on clinical outcomes (p for interaction = 0.36 for death; 0.20 for the composite of death, MI, or stroke; and 0.40 for repeat revascularization). In conclusion, there was no significant prognostic influence of diabetes on long-term treatment with DES or CABG in patients with multivessel CAD.

Relation of Routine, Periodic Fasting to Risk of Diabetes Mellitus, and Coronary Artery Disease in Patients Undergoing Coronary Angiography

2012-03-19

Previously we discovered that routine periodic fasting was associated with a lower prevalence of coronary artery disease (CAD). Other studies have shown that fasting increases longevity in animals. A hypothesis-generating analysis suggested that fasting may also associate with diabetes. This study prospectively tested whether routine periodic fasting is associated with diabetes mellitus (DM). Patients (n = 200) undergoing coronary angiography were surveyed for routine fasting behavior before their procedure. DM diagnosis was based on physician reports of current and historical clinical and medication data. Secondary end points included CAD (physician reported for ≥1 lesion of ≥70% stenosis), glucose, and body mass index (BMI). Meta-analyses were performed by evaluation of these patients and 448 patients from a previous study. DM was present in 10.3% of patients who fasted routinely and 22.0% of those who do not fast (odds ratio [OR] 0.41, 95% confidence interval [CI] 0.17 to 0.99, p = 0.042). CAD was found in 63.2% of fasting and 75.0% of nonfasting patients (OR 0.42, CI 0.21 to 0.84, p = 0.014), and in nondiabetics this CAD association was similar (OR 0.38, CI 0.16 to 0.89, p = 0.025). Meta-analysis showed modest differences for fasters versus nonfasters in glucose concentrations (108 ± 36 vs 115 ± 46 mg/dl, p = 0.047) and BMI (27.9 ± 5.3 vs 29.0 ± 5.8 kg/m2, p = 0.044). In conclusion, prospective hypothesis testing showed that routine periodic fasting was associated with a lower prevalence of DM in patients undergoing coronary angiography. A reported fasting association with a lower CAD risk was also validated and fasting associations with lower glucose and BMI were found.

Comparison of Late (3-Year) Registry Data Outcomes Using Bare Metal Versus Drug-Eluting Stents for Treating ST-Segment Elevation Acute Myocardial Infarctions

2012-03-22

Clinical trial data have supported the safety and efficacy of drug-eluting stents (DES) in the treatment of patients with ST-segment elevation myocardial infarctions (STEMIs), but contemporary “real-world” registry data regarding the late safety profiles of DES are limited. This prospective registry-based study included 1,569 consecutive unselected patients with STEMIs who underwent emergency primary percutaneous coronary intervention from January 2001 to December 2009. Of the study cohort, 200 patients (12.7%) received DES, while 1,369 patients (87.3%) underwent bare-metal stent (BMS) placement. The primary end points of the study were all-cause mortality and target vessel revascularization at 1, 2, and 3 years. Survival status was assessed by municipal civil registries. Repeat revascularization procedures were prospectively collected in the hospital database. All-cause mortality was significantly lower in the DES group at 3 years (4.2% vs 13.5%, p = 0.007) compared to BMS-treated patients, but DES use was not an independent predictor of all-cause mortality (adjusted odds ratio 0.5, 95% confidence interval 0.2 to 1.2, p = 0.10). Target vessel revascularization was significantly lower in the DES group compared to the BMS group at 3 years (10.5% vs 21%, p = 0.001). DES use was an independent predictor of reduced target vessel revascularization (adjusted odds ratio 0.44, 95% confidence interval 0.25 to 0.77, p = 0.004). Late definite stent thrombosis occurring after 1 year occurred in 4 (2.5%) patients in the DES group compared to 6 (0.7%) in the BMS group (p = 0.05). DES use was an independent predictor of late stent thrombosis (adjusted odds ratio 8.6, 95% confidence interval 1.9 to 38, p = 0.004). In conclusion, this contemporary registry-based study of patients who underwent primary percutaneous coronary intervention for STEMI demonstrated improved revascularization rates without increased 3-year hazard of adverse clinical outcomes in DES-treated patients.

Comparison of Frail Patients Versus Nonfrail Patients ≥65 Years of Age Undergoing Percutaneous Coronary Intervention

2012-03-22

Frailty is a geriatric syndrome characterized by functional impairments and is associated with poor outcomes; however, the prevalence of frailty and its association with health status in patients treated with percutaneous coronary intervention (PCI) are unknown. To assess the prevalence of frailty and its association with health status in PCI-treated patients, we studied 629 patients ≥65 years old undergoing PCI from October 2005 through September 2008. Frailty was characterized using the Fried criteria: weight loss >10 lbs. in previous 1 year, exhaustion, low physical activity, poor gait speed, and poor grip strength (3 features = frail; 1 feature to 2 features = intermediate frailty; 0 feature = not frail). Health status was assessed using the Short-Form 36 and the Seattle Angina Questionnaire (SAQ). Multivariable linear regression models were used to estimate the independent association between frailty and health status. Complete data on 545 patients demonstrated that 19% (n = 117) were frail, 47% (n = 298) had intermediate frailty, and 21% (n = 130) were not frail. Frail patients had more co-morbidities and more frequent left main coronary artery or multivessel disease after adjusting for age and gender (p <0.05 across groups). Multivariable linear regression demonstrated poorer health status in frail patients compared to nonfrail patients as evidenced by lower Short-Form 36 scores, lower SAQ scores for physical limitation, and lower SAQ scores for quality of life (p <0.001 for each health status domain). In conclusion, 1/5 of older patients are frail at the time of PCI and have greater comorbid burden, angiographic disease severity, and poorer health status than nonfrail adults.

Intravascular Ultrasound Findings That Are Predictive of No Reflow After Percutaneous Coronary Intervention for Saphenous Vein Graft Disease

2012-03-22

The aim of this study was to investigate the relation between intravascular ultrasound (IVUS) findings and the no-reflow phenomenon and long-term outcome after percutaneous coronary intervention (PCI) of saphenous vein graft (SVG) lesions. No reflow was defined as Thrombolysis In Myocardial Infarction grade 0, 1, or 2 flow after PCI. Of 311 patients who underwent IVUS before and after stenting, no reflow was observed in 39 patients (13%). Degenerated SVG (62% vs 36%, p = 0.002), IVUS-detected intraluminal mass (82% vs 43%, p <0.001), culprit lesion multiple plaque ruptures (23% vs 6%, p <0.001), and tissue prolapse (51% vs 35%, p = 0.043) were observed more frequently in patients with no reflow. In multivariate logistic regression analysis, an intraluminal mass (odds ratio [OR] 4.84, 95% confidence interval [CI] 1.98 to 10.49, p = 0.001), culprit lesion multiple plaque ruptures (OR 3.46, 95% CI 1.46 to 8.41, p = 0.014), and degenerated SVGs (OR 3.17, 95% CI 1.17 to 6.56, p = 0.024) were the independent predictors of no reflow after PCI. At 5-year clinical follow-up, rates of death (14, 36%, vs 55, 20%, p = 0.036) and myocardial infarction (13, 33%, vs 52, 19%, p = 0.039) were significantly higher in the no-reflow group. However, rate of target vessel revascularization was not significantly different between the 2 groups (15, 38%, vs 90, 33%, p = 0.3). IVUS-detected intraluminal mass, multiple plaque ruptures, and degenerated SVGs were associated with no reflow in SVG lesions after PCI. In conclusion, no reflow was associated with poor long-term clinical outcomes after PCI for SVG lesions.

Are the Results of a Regional ST-Elevation Myocardial Infarction System Reproducible?

2012-03-22

Primary percutaneous coronary intervention (PCI) is the preferred reperfusion method in patients with ST-elevation myocardial infarction (STEMI) if it can be performed in a timely manner in high-volume centers. Regional STEMI networks improve timely access to PCI but are frequently criticized for being single center. To determine if results of regional STEMI systems could be replicated and achieve similar outcomes in 2 separate geographic regions, we examined the prospective databases of 2 large regional STEMI networks that use identical standardized protocols and integrated transfer systems. The Minneapolis Heart Institute (MHI) database included 2,266 patients with STEMI from 31 hospitals (498 at the PCI hospital, 1,033 transferred from 11 hospitals <60 miles away, and 735 transferred from 19 hospitals 60 to 210 miles away). The Iowa Heart Center (IHC) database included 1,206 patients with STEMI from 24 hospitals (710 at the PCI hospital, 266 transferred from 10 hospitals <60 miles away, and 230 transferred from 13 hospitals 60 to 120 miles away). Median total door-to-balloon times for the PCI hospital, zone 1, and zone 2 patients were 64, 95, and 123 minutes for the MHI and 59, 102, and 136 for the IHC (p <0.05 for each comparison between MHI and IHC). Overall in-hospital, 30-day, and 1-year mortalities was 4.8%, 5.4%, and 8.0% respectively (p = NS for each comparison between MHI and IHC). In conclusion, the use of identical protocols in 2 large regional STEMI systems in geographically separate locations produced nearly identical outcomes, adding to evidence that regional STEMI centers expand timely access to PCI.

Recent Trends in Hospitalization for Acute Myocardial Infarction

Oliver J. Wang, Yongfei Wang, Jersey Chen, Harlan M. Krumholz — 2012-03-22

Rates of acute myocardial infarction (AMI) hospitalizations for elderly Medicare patients decreased during the previous decade. However, trends in population rates of AMI hospitalizations for all adults by subgroups have not been described. Using data from a large all-payer administrative database of hospitalizations, we calculated annual AMI hospitalization rates from 2001 through 2007. Trend analysis was performed across age, gender, and ethnicity categories using survey regression. Overall rate decreased from 314 to 222 AMI hospitalizations per 100,000 patients from 2001 through 2007, representing a 29.2% decrease. Significant decreases were observed in AMI hospitalization rate for each group by age categories (p <0.001) and by gender (p <0.001). When stratified by ethnicity and gender, age-adjusted AMI hospitalization rates in white men and women decreased by 30.8% and 31.4%, whereas black men and women had significantly slower rates of decrease of 13.6% and 12.6%, respectively. In conclusion, although the overall rate of AMI hospitalizations decreased from 2001 through 2007, the observed decrease was smaller for black patients compared to white patients across all age groups studied.

Within-Hospital and 30-Day Outcomes in 107,994 Patients Undergoing Invasive Coronary Angiography With Different Low-Osmolar Iodinated Contrast Media

2012-03-22

Comparative clinical outcomes after exposure to alternate low osmolar contrast media (LOCM) during invasive coronary angiography (ICA) and/or percutaneous coronary intervention (PCI) have been incompletely examined. From a retrospective multicenter observational study, we identified 107,994 adults without previous hemodialysis undergoing ICA and/or PCI with iohexol, iopamidol, or ioversol. We created a propensity score for contrast media type using age, gender, coverage status, route of hospitalization, illness severity, physician specialty, co-morbidities, and procedure type. Propensity matching was performed in a 1:1 fashion for iohexol (n = 10,204) and iopamidol (n = 10,204) and in a 1:1 fashion for iohexol (n = 19,482) and ioversol (n = 19,482). Groups were examined for differences in in-hospital mortality or subsequent hemodialysis, length of stay, and 30-day readmission for contrast-induced nephropathy (CIN). Compared to patients exposed to iohexol, no differences were observed for patients exposed to iopamidol or ioversol for in-hospital hemodialysis (0.5% vs 0.4%, p = 0.45; 0.3% vs 0.5%, p = 0.05), in-hospital mortality (0.7% vs 0.6%, p = 0.60; 0.5% vs 0.6%, p = 0.42), or composite hemodialysis or mortality (1.1% vs 1.0%, p = 0.58; 0.8% vs 1.0%, p = 0.06); for hospital length of stay (2.9 ± 2.7 vs 2.9 ± 2.7 days, p = 0.05; 2.8 ± 2.6 vs 2.9 ± 3.1 days, p = 0.35); or for 30-day readmission for CIN (0.1% vs 0.1%, p = 0.82; 0.1% vs 0.1%, p = 0.52). In conclusion, for patients undergoing ICA and/or PCI exposed to alternate LOCM, in-hospital death, need for hemodialysis, or readmission for CIN are uncommon, with no apparent clinical advantage among LOCM agents.

Comparison of Two- and Three-Dimensional Quantitative Coronary Angiography to Intravascular Ultrasound in the Assessment of Intermediate Left Main Stenosis

2012-03-19

Angiographic evaluation of intermediate left main coronary artery stenosis (LMS) is often limited. Three-dimensional (3D) quantitative coronary angiography has recently developed to overcome 2-dimensional (2D) quantitative coronary angiographic (QCA) limitations. In patients with angiographically intermediate LMS, we investigated whether 3D quantitative coronary angiography was superior to 2D quantitative coronary angiography in predicting the presence of a significant LMS, defined as a minimum luminal area <6 mm2 at intravascular ultrasound (IVUS). 2D and 3D quantitative coronary angiography were compared in their measurements of minimum luminal area, percent area stenosis, minimum luminal diameter, and percent diameter stenosis and in their prediction of an IVUS minimum luminal area <6 mm2. In total 58 target lesions were interrogated, 25 (43%) of which had an IVUS minimum luminal area <6 mm2. Correlation between 3D-QCA minimum luminal area and IVUS minimum luminal area was stronger than the correlation between 2D-QCA minimum luminal area (or minimum luminal diameter) and IVUS minimum luminal area (R = 0.67, p = 0.0001, and R = 0.40, p = 0.001, respectively, p = 0.04 for comparison). To predict IVUS minimum luminal area <6 mm2, the most accurate 2D-QCA measurement was minimum luminal diameter (area under curve 0.81, cutoff 2.2 mm, p = 0.0001), and the most accurate 3D-QCA measurement was minimum luminal area (area under curve 0.86, cutoff 5.6 mm2, p = 0.0001). 2D-QCA percent diameter stenosis did not significantly predict IVUS minimum luminal area <6 mm2 (area under curve 0.56, cutoff 38%, p = 0.45). In conclusion, the accuracy of quantitative coronary angiography in predicting LM IVUS minimum luminal area <6 mm2 is limited. When IVUS is not available or contraindicated, 3D quantitative coronary angiography may assist in the evaluation of intermediate LMS. Among 2D-QCA parameters, minimum luminal diameter is more accurate than percent diameter stenosis in predicting significant LMS.

Meta-Analysis of Dietary Glycemic Load and Glycemic Index in Relation to Risk of Coronary Heart Disease

Jia-Yi Dong, Yong-Hong Zhang, Peiyu Wang, Li-Qiang Qin — 2012-03-22

A high glycemic diet may increase cardiovascular risk, yet whether the risk differs by gender or adiposity is inconclusive. Our goal was to determine the associations between dietary glycemic load (GL) and glycemic index (GI), and coronary heart disease (CHD) risk by conducting a meta-analysis of prospective studies. We searched the PubMed and Embase databases in July 2011 to identify eligible studies. The random-effects model was used to calculate pooled relative risks (RRs) comparing the highest categories of exposure to the lowest. Prespecified subgroup analyses were performed by gender and body mass index. We identified 8 prospective studies for meta-analysis, consisting of 220,050 participants and 4,826 incident CHD cases. Pooled RRs of CHD in relation to dietary GL were 1.08 (95% confidence interval [CI] 0.92 to 1.27) for men, 1.69 (95% CI 1.32 to 2.16) for women, and 1.36 (95% CI 1.13 to 1.63) for men and women combined. For dietary GI, corresponding pooled RRs were 0.99 (95% CI 0.84 to 1.16), 1.26 (95% CI 1.12 to 1.43), and 1.13 (95% CI 1.00 to 1.28), respectively. Limited evidence suggested the associations appeared more evident in the overweight and obese. There was no indication of publication bias. In conclusion, high dietary GL and GI significantly increased the risk of CHD in women but not in men, and the unfavorable effects may be more pronounced in overweight and obese patients. Further studies are needed to verify these findings and elucidate the underlying mechanisms.

Effectiveness of Sotalol as First-Line Therapy for Fetal Supraventricular Tachyarrhythmias

2012-03-26

Fetal supraventricular tachycardia (SVT) and atrial flutter (AF) can be associated with significant morbidity and mortality. Digoxin is often used as first-line therapy but can be ineffective and is poorly transferred to the fetus in the presence of fetal hydrops. As an alternative to digoxin monotherapy, we have been using sotalol at presentation in fetuses with SVT or AF with, or at risk of, developing hydrops to attempt to achieve more rapid control of the arrhythmia. The present study was a retrospective review of the clinical, echocardiographic, and electrocardiographic data from all pregnancies with fetal tachycardia diagnosed and managed at a single center from 2004 to 2008. Of 29 affected pregnancies, 21 (16 SVT and 5 AF) were treated with sotalol at presentation, with or without concurrent administration of digoxin. Of the 21, 11 (6 SVT and 5 AF) had resolution of the tachycardia within 5 days (median 1). Six others showed some response (less frequent tachycardia, rate slowing, resolution of hydrops) without complete conversion. In 1 fetus with a slow response, the mother chose pregnancy termination. The 5 survivors with a slow response were all difficult to treat postnatally, including 1 requiring radiofrequency ablation as a neonate. One fetus developed blocked atrial extrasystoles after 1 dose of sotalol and was prematurely delivered for fetal bradycardia. Three grossly hydropic fetuses with SVT showed no response and died within 1 to 3 days of treatment. In conclusion, transplacental sotalol, alone or combined with digoxin, is effective for the treatment of fetal SVT and AF, with an 85% complete or partial response rate in our series.

Relation of Dosing of the Renin–Angiotensin System Inhibitors After Cardiac Resynchronization Therapy to Long-Term Prognosis

Lilian Mantziari, Kaushik Guha, Zohya Khalique, Theresa McDonagh, Rakesh Sharma — 2012-04-02

Dosing of angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) in patients with heart failure (HF) treated with cardiac resynchronization therapy (CRT) may affect long-term outcomes. Retrospective data were collected at baseline and follow-up for consecutive patients who had CRT implanted and attended the institutional specialist HF pacing clinic. The study end point was death from any cause or hospitalization for worsening HF 24 months after implantation. Ninety-one patients (72 men, 68 ± 12 years old) with decreased left ventricular ejection fraction (24 ± 6%) were included. At baseline 85 patients (93%) were on ACE inhibitors/ARBs. At 6 months 3 patients had died and 86 of 88 (98%) were on ACE inhibitors/ARBs. Doses were uptitrated from 55 ± 35% of target dose (TD) at baseline to 62 ± 31% TD at month 6 (p = 0.018), whereas blood pressure was unchanged. Patients treated with <50% TD of ACE inhibitors/ARBs (n = 20) at month 6 had worse 24-month event-free survival than those on 50% to 99% TD (n = 38, p = 0.011, log-rank test) or ≥100% TD (n = 30, p = 0.007, log-rank test). Failure to achieve a dose ≥50% TD of ACE inhibitors/ARBs at 6 months after CRT implantation was an independent predictor of all-cause mortality or hospitalization (hazard ratio 3.99, 95% confidence interval 1.66 to 9.62, p = 0.002) after adjustment for potential confounders including age, estimated glomerular filtration rate, diabetes and New York Heart Association class. In conclusion optimal dosing of ACE inhibitors/ARBs is an independent predictor of prognosis in patients with HF treated with CRT and it can be achieved by a structured follow-up within a specialized HF pacing clinic.

Comparison of Left Ventricular Outflow Geometry and Aortic Valve Area in Patients With Aortic Stenosis by 2-Dimensional Versus 3-Dimensional Echocardiography

2012-03-22

The present study sought to elucidate the geometry of the left ventricular outflow tract (LVOT) in patients with aortic stenosis and its effect on the accuracy of the continuity equation-based aortic valve area (AVA) estimation. Real-time 3-dimensional transesophageal echocardiography (RT3D-TEE) provides high-resolution images of LVOT in patients with aortic stenosis. Thus, AVA is derived reliably with the continuity equation. Forty patients with aortic stenosis who underwent 2-dimensional transthoracic echocardiography (2D-TTE), 2-dimensional transesophageal echocardiography (2D-TEE), and RT3D-TEE were studied. In 2D-TTE and 2D-TEE, the LVOT areas were calculated as π × (LVOT dimension/2)2. In RT3D-TEE, the LVOT areas and ellipticity ([diameter of the anteroposterior axis]/[diameter of the medial-lateral axis]) were evaluated by planimetry. The AVA is then determined using planimetry and the continuity equation method. LVOT shape was found to be elliptical (ellipticity of 0.80 ± 0.08). Accordingly, the LVOT areas measured by 2D-TTE (median 3.7 cm2, interquartile range 3.1 to 4.1) and 2D-TEE (median 3.7 cm2, interquartile range 3.1 to 4.0) were smaller than those by 3D-TEE (median 4.6 cm2, interquartile range 3.9 to 5.3; p <0.05 vs both 2D-TTE and 2D-TEE). RT3D-TEE yielded a larger continuity equation-based AVA (median 1.0 cm2, interquartile range 0.79 to 1.3, p <0.05 vs both 2D-TTE and 2D-TEE) than 2D-TTE (median 0.77 cm2, interquartile range 0.64 to 0.94) and 2D-TEE (median 0.76 cm2, interquartile range 0.62 to 0.95). Additionally, the continuity equation-based AVA by RT3D-TEE was consistent with the planimetry method. In conclusion, RT3D-TEE might allow more accurate evaluation of the elliptical LVOT geometry and continuity equation-based AVA in patients with aortic stenosis than 2D-TTE and 2D-TEE.

Frequency of Congenitally Bicuspid Aortic Valves in Patients ≥80 Years of Age Undergoing Aortic Valve Replacement for Aortic Stenosis (With or Without Aortic Regurgitation) and Implications for Transcatheter Aortic Valve Implantation

2012-03-29

The purpose of the present report was to determine the frequency of a congenitally bicuspid aortic valve in patients ≥80 years of age old with aortic stenosis (AS) severe enough to warrant aortic valve replacement. Transcatheter aortic valve implantation (TAVI) has traditionally been reserved for patients ≥80 years of age with severe AS involving a 3-cuspid aortic valve. Traditionally, AS involving a 2-cuspid aortic valve has been a contraindication to TAVI. We examined operatively excised stenotic aortic valves in 364 patients aged ≥80 years to determine the frequency of an underlying congenitally bicuspid aortic valve. Of the 347 octogenarians and 17 nonagenarians, 78 (22%) and 3 (18%) had stenotic congenitally bicuspid aortic valves, respectively. In conclusion, because the results of TAVI are less favorable in patients with stenotic congenitally bicuspid valves than in patients with stenotic tricuspid aortic valves, proper identification of the underlying aortic valve structure is important when considering TAVI as a therapeutic procedure for AS in older patients.

Frequency and Causes of Stroke During or After Transcatheter Aortic Valve Implantation

2012-03-19

Transcatheter aortic valve implantation (TAVI) is invariably associated with the risk of clinically manifest transient or irreversible neurologic impairment. We sought to investigate the incidence and causes of clinically manifest stroke during TAVI. A total of 214 consecutive patients underwent TAVI with the Medtronic-CoreValve System from November 2005 to September 2011 at our institution. Stroke was defined according to the Valve Academic Research Consortium recommendations. Its cause was established by analyzing the point of onset of symptoms, correlating the symptoms with the computed tomography-detected defects in the brain, and analyzing the presence of potential coexisting causes of stroke, in addition to a multivariate analysis to determine the independent predictors. Stroke occurred in 19 patients (9%) and was major in 10 (5%), minor in 3 (1%), and transient (transient ischemic attack) in 6 (3%). The onset of symptoms was early (≤24 hours) in 8 patients (42%) and delayed (>24 hours) in 11 (58%). Brain computed tomography showed a cortical infarct in 8 patients (42%), a lacunar infarct in 5 (26%), hemorrhage in 1 (5%), and no abnormalities in 5 (26%). Independent determinants of stroke were new-onset atrial fibrillation after TAVI (odds ratio 4.4, 95% confidence interval 1.2 to 15.6), and baseline aortic regurgitation grade III or greater (odds ratio 3.2, 95% confidence interval 1.1 to 9.3). In conclusion, the incidence of stroke was 9%, of which >1/2 occurred >24 hours after the procedure. New-onset atrial fibrillation was associated with a 4.4-fold increased risk of stroke. In conclusion, these findings indicate that improvements in postoperative care after TAVI are equally, if not more, important for the reduction of periprocedural stroke than preventive measures during the procedure.

A Novel Titin Mutation in Adult-Onset Familial Dilated Cardiomyopathy

2012-04-05

Familial dilated cardiomyopathy is a major cause of advanced heart failure and heart transplantation. In most families, the disease-causing mutation is unknown, and relatives should therefore undergo periodic screening to facilitate early diagnosis and therapy. In the present study, we describe a novel titin truncation mutation causing adult-onset familial dilated cardiomyopathy in an Israeli Arab family. The family members underwent physical examination, electrocardiography, and Doppler echocardiography. Linkage to candidate loci was performed, followed by gene sequencing. We identified 13 clinically affected family members (8 men and 5 women, mean age 47 ± 12 years). Compared with their healthy first-degree relatives, the affected relatives had a larger end-diastolic left ventricular dimension (60 ± 10 vs 49 ± 4 mm, p <0.001), lower ejection fraction (43 ± 11% vs 60 ± 6%, p <0.001), and markedly higher end-systolic volume indexes but no difference in wall thickness or diastolic function. The linkage studies or direct sequencing excluded LMNA, MYH7, TNNT2, TNNI3, SCN5A, DES, SGCD, ACTC, PLN, and MYH6 but established linkage to the TTN locus at chromosome 2q31, yielding a maximum (2-point) LOD score of 3.44. Sequence analysis identified an insertion (c.58880insA), causing protein truncation after 19,628 amino acids (p.S19628IfsX1). No founder effect was found among the Israeli Arabs. In conclusion, titin is a giant protein with a key role in sarcomere assembly, force transmission, and maintenance of resting tension. Although some mutations result in skeletal myopathy, others cause isolated, maturity-onset cardiomyopathy.

Usefulness of Sum of ST-Segment Elevation on Electrocardiograms (Limb Leads) for Predicting In-Hospital Complications in Patients With Stress (Takotsubo) Cardiomyopathy

2012-03-22

Although the prognosis of patients with stress (takotsubo) cardiomyopathy is relatively favorable, serious complications occur in some patients. It is generally accepted that electrocardiography is an essential tool for the diagnosis of stress cardiomyopathy, with findings highly suggestive of the characteristics of myocardial damage. We tested the hypothesis that the quantitative analysis of electrocardiograhic changes can predict complications in stress cardiomyopathy. The study subjects were 85 patients with stress cardiomyopathy. A total of 34 patients developed ≥1 in-hospital complications (heart failure, intraventricular pressure gradient [>30 mm Hg], cardiogenic shock, ventricular tachycardia/fibrillation, and embolism). Patients with complications were likely to have a higher heart rate (96 ± 25 vs 76 ± 17 beats/min, p <0.001), larger sum of ST-segment elevation in 12 leads (median 10.5 mm; interquartile range 5.0 to 17.5 vs 3.0 mm, interquartile range 0 to 7.0; p <0.001) and extension of ST-segment elevation to limb leads (50% vs 12%, p <0.001) than those without complications. Multivariate logistic regression analysis identified heart rate (odds ratio 1.05, 95% confidence interval 1.02 to 1.07, p = 0.001) and sum of ST-segment elevation in 12 leads (odds ratio 1.24, 95% confidence interval 1.11 to 1.39, p <0.001) as significant and independent predictors of complications. Receiver operating characteristic analysis selected 5.5 mm as the best cutoff value of sum of ST-segment elevation in 12 leads for the prediction of complications, with a sensitivity and specificity of 74% and 73%, respectively, and area under the curve of 0.81 (95% confidence interval 0.72 to 0.90, p <0.001). The results suggest that the extent and magnitude of ST-segment elevation on the electrocardiogram are potentially useful predictors of in-hospital complications in patients with stress cardiomyopathy.

Social Burden and Lifestyle in Adults With Congenital Heart Disease

2012-03-26

We aimed to evaluate how the presence and severity of congenital heart disease (CHD) influence social life and lifestyle in adult patients. A random sample (n = 1,496) from the CONgenital CORvitia (n = 11,047), the Dutch national registry of adult patients with CHD, completed a questionnaire on educational attainment, employment and marital statuses, and lifestyle (response 76%). The Utrecht Health Project provided a large reference group (n = 6,810) of unaffected subjects. Logistic regression models were used for subgroup analyses and to adjust for age, gender, and socioeconomic status where appropriate. Of all patients 51.5% were men (median age 39 years, interquartile range 29 to 51) with mild (46%), moderate (44%), and severe (10%) CHD. Young (<40-year-old) patients with CHD were more likely to have achieved a lower education (adjusted odds ratios [ORs] 1.6 for men and 1.9 for women, p <0.05 for the 2 comparisons), significantly more often unemployed (adjusted ORs 5.9 and 2.0 for men and women, respectively), and less likely to be in a relationship compared to the reference group (adjusted ORs 8.5 for men and 4.5 for women). These poorer outcomes were seen in all severity groups. Overall, the CHD population smoked less (adjusted OR 0.5, p <0.05), had more sports participation (adjusted OR 1.2, p <0.05), and had less obesity (adjusted OR 0.7, p <0.05) than the reference group. In conclusion, there was a substantial social disadvantage in adult patients with CHD, which was seen in all severity groups and primarily in young men. In contrast, adults with CHD had healthier lifestyles compared to the reference group.

Gender and Ethnic Differences in Red Cell Distribution Width and Its Association With Mortality Among Low Risk Healthy United State Adults

2012-03-19

Limited information is available about gender and ethnic differences in red cell distribution width (RCDW) with regard to its relation to mortality in a population free of cardiovascular (CV) disease and diabetes. To assess gender and ethnic differences in RCDW and their effect on the association between RCDW and mortality, the Third National Health and Nutritional Examination Survey (n = 15,460, 1988 to 1994) data were examined. Multivariate adjusted Cox proportional hazard analysis was performed to assess effect of gender and ethnicity on the association between RCDW and mortality (total, CV disease, and coronary heart disease [CHD]). RCDW (mean ± SE) was greater in black women (13.1 ± 0.03) and men (13.4 ± 0.02) compared to women of white (12.9 ± 0.02) and other (13.0 ± 0.07) ethnicities and men of white (13.3 ± 0.02) and other (13.3 ± 0.07) ethnicities, respectively (p <0.001). The interaction between RCDW and gender was statistically significant for all study outcomes (p <0.001) but nonsignificant for RCDW and ethnicity. After adjusting for key variables, RCDW in women was associated with adjusted hazard ratios of 1.22 (95% confidence interval [CI] 1.14 to 1.31) for all-cause mortality, 1.17 (95% CI 1.07 to 1.28) for CV deaths, and 1.18 (95% CI 1.03 to 1.35) for CHD deaths; in men, adjusted hazard ratios were 1.29 (95% CI 1.20 to 1.38) for all-cause mortality, 1.27 (95% CI 1.17 to 1.37) for CV deaths, and 1.25 (95% CI 1.13 to 1.39) for CHD deaths (p <0.05 for all). In conclusion, blacks and men have significantly greater RCDWs compared to whites and women. Greater RCDW is associated with a greater risk of mortality in men compared to women, whereas no effect modification is observed by ethnicity.

Relation of Ventricular Ectopic Complexes to QTc Interval on Ambulatory Electrocardiograms in Williams Syndrome

R. Thomas Collins, Peter F. Aziz, Christopher J. Swearingen, Paige B. Kaplan — 2012-03-30

Williams syndrome (WS) is a congenital, developmental disorder affecting 1 in 8,000 live births. The corrected QT (QTc) interval is prolonged in 13% of patients with WS. No data exist characterizing the ambulatory electrocardiographic findings in WS. A retrospective review of all patients with WS evaluated at our institution from January 1, 1980 to December 31, 2007 was performed. Patients with ≥1 ambulatory electrocardiogram (AECG) with sinus rhythm and measurable intervals were included. QTc measurements were made at the minimum and maximum heart rate. Logistic regression analysis was used to evaluate the correlation of ventricular ectopic complexes with QTc measurements. A statistical probability of p <0.05 was considered significant. Of 270 patients identified, 32 had AECGs available for review. Complete data were available for 56 AECGs from 26 patients (15 female; 58%). Their mean age was 15.6 ± 7.2 years at the initial AECG and 20.6 ± 8.6 years for all AECGs. The QTc interval increased with increasing heart rate. Ventricular premature complexes occurred in 40 (73%) of 56 AECGs and 21 (81%) of 26 patients. Ventricular tachycardia occurred in 5 (9%) of 56 AECGs and 4 (15%) of 26 patients. The mean length of ventricular tachycardia was 3.6 ± 0.5 beats at a rate of 171 ± 40 beats/min. The QTc interval at the minimum heart rate correlated directly with age (p <0.001), total ventricular premature complexes (p = 0.007), ventricular couplets (p = 0.002), and ventricular tachycardia (p = 0.011). The QTc interval at the maximum heart rate correlated directly with age (p <0.001), total ventricular premature complexes (p = 0.016), and ventricular couplets (p = 0.006). In conclusion, the QTc interval correlated with ventricular ectopic complexes in patients with WS. The type of ventricular ectopic complexes suggested an alternate etiology of the QTc prolongation seen in WS from that seen in congenital long QT syndrome.

Recessively Inherited Severe Aortic Aneurysm Caused by Mutated EFEMP2

2012-03-22

Familial aortic aneurysm (AA) is mostly inherited as an autosomal dominant disorder. However, recessively inherited AA has also been observed but in association with skin manifestations of cutis laxa, which is caused by a mutated EFEMP2 gene. In the present study, we recruited 9 patients, from 4 unrelated consanguineous families, with recessively inherited AA. The index cases, their parents, and siblings underwent clinical evaluation and cardiac imaging. In the affected subjects, the clinical presentation ranged from sweating and cyanosis at 3 months of age to incidental findings in an asymptomatic adult. The echocardiogram revealed a wide spectrum of severity of the AA, with a Z-score varying from 5 to 33. Intrafamilial variability was also evident; 2 unrelated subjects were detected at 17 and 20 years of age through family screening. The skin manifestations of cutis laxa were not found in any patient. In 1 family, genome-wide single-nucleotide polymorphism analysis detected a homozygous block, shared by 2 affected siblings, on chromosome 11 at q13. Sequence analysis of EFEMP2, located on chromosome 11 at q13, identified a novel homozygous mutation (p.E161K) in all 9 affected subjects. In this largest cohort of reported patients with a mutated EFEMP2 gene, we illustrate the phenotypic spectrum of inherited AA due to a novel EFEMP2 mutation. In conclusion, our work suggests that in families with apparently recessively inherited AA, molecular analysis of EFEMP2 gene might be warranted.

Clinical Implications of Cardiovascular Preventing Pleiotropic Effects of Dipeptidyl Peptidase-4 Inhibitors

Steven G. Chrysant, George S. Chrysant — 2012-03-19

Dipeptidyl peptidase-4 (DPP-4) inhibitors are novel drugs for the treatment of type 2 diabetes mellitus. They exert their action through inhibition of the catabolism of locally secreted incretins such as glucagon-like peptide-4 (GLP-4) and glucose-dependent insulinotropic polypeptide (GIP) by inhibiting enzyme DPP-4. GLP-1 and GIP are secreted from the gastrointestinal tract in response to food intake. GLP-1 is secreted from L cells present in the mucosa of the small intestine and colon, whereas GIP is secreted from K cells of the jejunum. These 2 incretins lower blood glucose levels and postprandial hyperglycemia by stimulating insulin release from b cells of the pancreas, thus increasing insulin sensitivity, delaying gastrointestinal emptying, decreasing food intake through early satiety, and causing weight loss in the long term. However, their action is short-lived (2 to 3 minutes) because of catabolism by the DPP-4 enzyme. The importance of DPP-4 inhibitors lies in their blockade of the DPP-4 enzyme leading to the prevention of their catabolism and thus increasing their blood levels, extending the duration of their action, and improving their blood glucose-lowering effect. In addition to their antidiabetic action, recent experimental and clinical studies have demonstrated a pleiotropic cardiovascular protective effect of these agents independent of their antidiabetic action. They prevent atherosclerosis, improve endothelial dysfunction, lower blood pressure, and prevent myocardial injury. All these actions are discussed in this concise review. In conclusion, DPP-4 inhibitors are novel antidiabetic agents with pleiotropic cardiovascular protective effects in addition to their antidiabetic action.

Needed—Electrocardiographic Findings in Left Ventricular Noncompaction

John E. Madias — 2012-06-01

This comment is in response to the contribution by Greutmann et al in the January 15, 2012, issue of The American Journal of Cardiology on adverse outcomes in 155 patients with isolated left ventricular (LV) noncompaction, 77% of whom were symptomatic when their condition was identified. At a median follow-up time of 2.7 years, none of the asymptomatic and 31% of the symptomatic patients had died or undergone transplantation. The major determinants of these 2 outcomes were presentation with a cardiovascular complication, New York Heart Association class ≥III. As in a study by Stöllberger et al recently published in the Journal, the electrocardiographic data are scanty. Indeed, the investigators listed in Tables 1, 2, and 4 only atrial fibrillation and bundle branch block (type not specified) and in Table 3 sustained ventricular tachycardia. It would have been appropriate at least to report on LV hypertrophy, considering that their symptomatic patients had higher rates of LV dilatation and decreased LV ejection fractions. The investigators refer to “the thickened 2-layered myocardium consisting of a thin compacted outer (epicardial) and a much thicker noncompacted inner (endocardial) layer with a deep intratrabecular recesses”; is it possible that the intraventricular conduction is affected in patients with LV noncompaction because of alterations in the extent, distribution, or functional characteristics of the Purkinje network or the absolute thickness of the compacted and noncompacted myocardial layers? Stöllberger et al reported on the presence of left bundle branch block and Q waves in their patients. Could Greutmann et al oblige by supplying information on the frequency of LV hypertrophy, Q waves, left bundle branch block, right bundle branch block, and left anterior and posterior hemiblocks, as well as QRS duration, QT interval, corrected QT interval, and PR interval, in their patients?

Authors' Reply

Matthias Greutmann, Christine H. Attenhofer Josb, Rolf Jenni, Erwin N. Oechslin — 2012-06-01

We wish to thank Dr. Madias for his interest in our report. With regard to electrocardiographic data, the types of bundle branch block were specified in the footnote of Table 1 (of 32 patients with bundle branch block, 28 had left bundle branch block and 4 had right bundle branch block). Table 3 lists major adverse cardiovascular events, which includes sustained ventricular arrhythmias.

Thromboembolic Risk in Atrial Flutter Resembles Non-Valvular Atrial Fibrillation (Insights from Transesophageal Echocardiography)

Rui Providência — 2012-06-01

The recently published report by Parikh et al reinforces the thromboembolic nature of atrial flutter. The described prevalence of left atrial (LA) thrombi and spontaneous echocardiographic contrast (SEC) in this population presenting with a mean CHADS2 score of 1.62 ± 1.18 and a mean CHA2DS2-VASc score of 2.67 ± 1.55 was 5.3% and 25.9%, respectively.

Cardiovascular Death and Cancer Death—Competing Risk?

Franz H. Messerli, Sripal Bangalore — 2012-06-01

Drs. Nabel and Braunwald have elegantly illustrated in their Figure 1 that preventive and therapeutic strategies substantially reduced risk for cardiovascular death. In contrast, the death rate from cancer has remained unchanged since 1958. The ratio between cardiovascular death and cancer death has decreased by 45% (from 2.9 to 1.6) over 25 years, and now more and more individuals die of cancer who previously died of cardiovascular disease. The more efficacious cardiovascular drugs are (i.e., the better they protect against cardiovascular death), the more they will increase life expectancy and thus the risk for cancer (pseudocarcinogenicity). Should this pattern continue at the same pace, cancer is prone to strip heart disease of its status as the number 1 killer of Americans. This transition has already happened in Canada, where in 2008 for the first time, cancer was the leading cause of death in every province and territory. The seminal notion of the American Heart Association that “in the past 100 years, only during the 1918 flu pandemic cardiovascular disease was not the number-one cause of death” may rapidly become futile.

Erratum for Ito et al. “Comparison of Patients With Pulmonary Arterial Hypertension With Versus Without Right-Sided Mechanical Alternans” Am J Cardiol 2012;109:428–431

2012-06-01

The wording of the second and third column headings in was incorrect. The second column heading should have read “No Alternans (n = 24)” and the third column heading should have read “Alternans (n = 8).”

Editorial Board

2012-06-01

American Journal of Cardiology

Eugene Braunwald, MD and the Early Years of Hypertrophic Cardiomyopathy: A Conversation With Dr. Barry J. Maron

Influence of Diabetes Mellitus on Long-Term (Five-Year) Outcomes of Drug-Eluting Stents and Coronary Artery Bypass Grafting for Multivessel Coronary Revascularization

Relation of Routine, Periodic Fasting to Risk of Diabetes Mellitus, and Coronary Artery Disease in Patients Undergoing Coronary Angiography

Comparison of Late (3-Year) Registry Data Outcomes Using Bare Metal Versus Drug-Eluting Stents for Treating ST-Segment Elevation Acute Myocardial Infarctions

Comparison of Frail Patients Versus Nonfrail Patients ≥65 Years of Age Undergoing Percutaneous Coronary Intervention

Intravascular Ultrasound Findings That Are Predictive of No Reflow After Percutaneous Coronary Intervention for Saphenous Vein Graft Disease

Are the Results of a Regional ST-Elevation Myocardial Infarction System Reproducible?

Recent Trends in Hospitalization for Acute Myocardial Infarction

Within-Hospital and 30-Day Outcomes in 107,994 Patients Undergoing Invasive Coronary Angiography With Different Low-Osmolar Iodinated Contrast Media

Comparison of Two- and Three-Dimensional Quantitative Coronary Angiography to Intravascular Ultrasound in the Assessment of Intermediate Left Main Stenosis

Meta-Analysis of Dietary Glycemic Load and Glycemic Index in Relation to Risk of Coronary Heart Disease

Effectiveness of Sotalol as First-Line Therapy for Fetal Supraventricular Tachyarrhythmias

Relation of Dosing of the Renin–Angiotensin System Inhibitors After Cardiac Resynchronization Therapy to Long-Term Prognosis

Comparison of Left Ventricular Outflow Geometry and Aortic Valve Area in Patients With Aortic Stenosis by 2-Dimensional Versus 3-Dimensional Echocardiography

Frequency of Congenitally Bicuspid Aortic Valves in Patients ≥80 Years of Age Undergoing Aortic Valve Replacement for Aortic Stenosis (With or Without Aortic Regurgitation) and Implications for Transcatheter Aortic Valve Implantation

Frequency and Causes of Stroke During or After Transcatheter Aortic Valve Implantation

A Novel Titin Mutation in Adult-Onset Familial Dilated Cardiomyopathy

Usefulness of Sum of ST-Segment Elevation on Electrocardiograms (Limb Leads) for Predicting In-Hospital Complications in Patients With Stress (Takotsubo) Cardiomyopathy

Social Burden and Lifestyle in Adults With Congenital Heart Disease

Gender and Ethnic Differences in Red Cell Distribution Width and Its Association With Mortality Among Low Risk Healthy United State Adults

Relation of Ventricular Ectopic Complexes to QTc Interval on Ambulatory Electrocardiograms in Williams Syndrome

Recessively Inherited Severe Aortic Aneurysm Caused by Mutated EFEMP2

Clinical Implications of Cardiovascular Preventing Pleiotropic Effects of Dipeptidyl Peptidase-4 Inhibitors

Needed—Electrocardiographic Findings in Left Ventricular Noncompaction

Authors' Reply

Thromboembolic Risk in Atrial Flutter Resembles Non-Valvular Atrial Fibrillation (Insights from Transesophageal Echocardiography)

Cardiovascular Death and Cancer Death—Competing Risk?

Erratum for Ito et al. “Comparison of Patients With Pulmonary Arterial Hypertension With Versus Without Right-Sided Mechanical Alternans” Am J Cardiol 2012;109:428–431

Editorial Board

Contents