Starting today, you will be able to subscribe to the Cardiovascular Medicine feed through Twitter.

What is Twitter? It is a micro-blogging site designed to rapidly disseminate news to subscribers. More information can be found here.

Create a log-in for yourself, follow the Cardiovascular Medicine feed and you are guaranteed to receive the updates as soon as they are posted. Please feel free to pass the links to your colleagues.

Cardiovascular Medicine is proud to continue updating you on all the relevant information in the field of cardiology.

Further information: Anatomy of the Heart (see p3) from Cardiovascular Medicine, 3rd Edn*

In order to determine whether or not new cardiomyocytes are formed during the lifetime of a human heart, this study was conducted to establish whether humans are limited to the heart muscle cells present at birth, or if cardiomyocytes are generated later in life also. Although cells in rodents have been tagged with labeled nucleotide analogs for several decades, and studies have indicated that regeneration of cardiomyocytes occurs postnatally, results have been conflicting. In humans, scientists have known that in childhood, cardiomyocytes grow bigger through a process called hypertrophy, but cells had not been observed dividing. In addition, when cardiomyocytes die as a result of a heart attack, scar tissue forms instead of heart muscle cells, and thus, the heart is weakened. Also, the proliferation that would be needed to create cardiac tumors is not usually seen. In humans, cell turnover has been difficult to study because the use of labeled nucleotide analogs, such as those used in experimental animals, cannot be used in humans due to safety concerns.

To establish the age of cardiomyocytes in humans, the authors [1] took advantage of the integration of carbon-14 into human DNA that was generated by nuclear bomb testing during the 1950s. They found that the regeneration of cardiomyocytes in humans does occur postnatally, but is insufficient to keep the heart muscle intact functionally. Cardiomyocytes renew in gradually decreasing numbers, i.e. 1% of a human’s cardiomyocytes have an annual turnover by age 25, but the number decreases to 0.45% by age 75. Fewer than 50% of cardiomyocytes are exchanged during a normal life-span. It is encouraging that cardiomyocytes have the capacity to regenerate, and it is important that researchers work to develop pharmacologic strategies to stimulate the process, thereby allowing a higher percentage of injured or dying heart muscle cells to be replaced in this manner.

[1] Bergmann O, Bhardwaj RD, Bernard S et al. Evidence for cardiomyocyte renewal in humans. Science 2009;324:98-102

Note: You may need subscriptions to access content from links on this page. You are responsible for obtaining these subscriptions.

* To view the online text from the book, please navigate to SpringerLink or use the DVD to access electronic content. SpringerLink is a subscription service. For further information, click here.

Further information: Drug-Eluting Coronary Stents (see p1031) from Cardiovascular Medicine, 3rd Edn*

In patients with multivessel coronary artery disease (CAD), it is important to determine which vessels have stenotic coronary lesions that induce ischemia and thus warrant stenting, and which vessels do not. Currently, coronary angiography is the standard method used to determine the vessels in which stents should be placed.

The objective of this study [1] was to compare treatment that is based on fractional flow reserve (FFR) measurement plus angiography to the current practice of treatment that is guided only by angiography. FFR is defined as the ratio of maximal blood flow in a stenotic artery to normal maximal flow. It can be easily measured during coronary angiography by calculating the ratio of distal coronary pressure measured with a guidewire to aortic pressure measured simultaneously with the guiding catheter. The Fractional flow reserve versus Angiography for Multivessel Evaluation (FAME) study was conducted to determine if the measurement of FFR used in addition to angiography improves outcomes in patients undergoing percutaneous coronary angiography (PCI). From January 2006 through September 2007, one thousand five patients were enrolled in 20 centers in the US and Europe. Of those 1005 patients, 496 were randomized to angiography-guided PCI and 509 to FFR-PCI. The primary endpoint was the rate of major adverse cardiac events (composite of death, nonfatal myocardial infarction, and repeat revascularization) at 1 year.

In both groups, the baseline characteristics, number of lesions, vessel and lesion dimensions as assessed by quantitative coronary angiography, and severity of coronary artery disease as indicated by the SYNTAX score were similar. The mean (±SD) number of indicated lesions per patient was 2.7±0.9 in the angiography group and 2.8±1.0 in the FFR group (P=0.34). The number of stents used per patient was 2.7±1.2 and 1.9±1.3, respectively (P<0.001). The 1-year event rate was 18.3% (91 patients) in the angiography group and 13.2% (n=67) of patients in the FFR group (P=0.02). Seventy-eight percent of the patients in the angiography group were free from angina at 1 year, as compared with 81% of patients in the FFR group (P=0.20).

The results of the study showed that in patients with multivessel CAD, measurement of FFR during PCI, as compared with the standard practice of angiography-guided PCI only, significantly reduced the rate at one year of the primary end point of death, nonfatal myocardial infarction, and repeat revascularization.

[1] Tonino PAL, De Bruyne B, Pijls NHJ et al. Fractional flow reserve versus angiography for guiding percutaneous coronary intervention. N Engl J Med 2009;360:213-24

Note: You may need subscriptions to access content from links on this page. You are responsible for obtaining these subscriptions.

* To view the online text from the book, please navigate to SpringerLink or use the DVD to access electronic content. SpringerLink is a subscription service. For further information, click here.

Further information: Sudden Cardiac Death (see p2039) from Cardiovascular Medicine, 3rd Edn*

This study [1] is a large, retrospective cohort study intended to compare the two classes of antipsychotic drugs, typical and atypical, and the associated risk of sudden cardiac death in patients using each class of medication. Typical antipsychotic drugs are known to block repolarizing potassium currents in vitro and prolong the QT interval, a mechanism causing ventricular tachyarrhythmias that lead to sudden death. These drugs also cause serious movement disorders, another limiting factor in their use. Atypical antipsychotic drugs are less likely to cause movement disorders, thus are considered safer, and they have largely replaced the older, typical drugs in clinical practice. Although a link had been established between the use of atypical drugs and both torsades de pointes and sudden cardiac death, the atypical drugs were thought to have a lower risk.

Study data were obtained from computerized files of Tennessee Medicaid of individuals who had enrolled from January 1, 1990 through December 31, 2005. Only people of 30–74 years of age were included in this study. The primary analysis included 44,218 and 46,089 baseline users of single typical and atypical drugs, respectively, and 186,600 matched nonusers of antipsychotic drugs. A secondary analysis of users of antipsychotic drugs who had no baseline diagnosis of schizophrenia or related psychoses and with whom users were matched according to propensity score was conducted to assess residual confounding related to factors associated with the use of antipsychotic drugs.

Current users of typical and atypical antipsychotic drugs had higher rates of sudden cardiac death than did nonusers of antipsychotic drugs, with adjusted incidence-rate ratios of 1.99 (95% confidence interval [CI], and 1.68–2.34) and 2.26 (95% CI, 1.88–2.72), respectively. The incidence-rate ratio for users of atypical antipsychotic drugs as compared with users of typical antipsychotic drugs was 1.14 (95% CI, 0.93–1.39). Former users of antipsychotic drugs had no significantly increased risk (incidence-rate ratio, 1.13; 95% CI, 0.98–1.30). For both classes of drugs, the risk for current users increased significantly with an increasing dose. Among users of typical antipsychotic drugs, the incidence-rate ratios increased from 1.31 (95% CI, 0.97–1.77) for those taking low doses to 2.42 (95% CI, 1.91–3.06) for those taking high doses (P<0.001). Among users of atypical drugs, the incidence-rate ratios increased from 1.59 (95% CI, 2.25–3.65) for those taking high doses (P=0.01). The findings were similar in the cohort that was matched for propensity score.

The study concluded that a similar dose-related increased risk of sudden cardiac death was present in both typical and atypical antipsychotic drugs.

[1] Ray WA, Chung CP, Murray KT et al. Atypical antipsychotic drugs and the risk of sudden cardiac death. N Engl J Med 2009;360:225-35

Note: You may need subscriptions to access content from links on this page. You are responsible for obtaining these subscriptions.

* To view the online text from the book, please navigate to SpringerLink or use the DVD to access electronic content. SpringerLink is a subscription service. For further information, click here.

Further information: Drug-Eluting Coronary Stents (see p1031) from Cardiovascular Medicine, 3rd Edn*

The Synergy Between PCI with Taxus and Cardiac Surgery (SYNTAX) trial [1] compared two revascularization strategies for treating patients with previously untreated three-vessel or left main coronary artery disease (CAD), percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG). While CABG has been the treatment of choice for such patients with severe CAD, improvements in PCI have led to expanded use of the procedure in these patients, but adequately powered randomized trials to support its use have not been performed. The SYNTAX trial assessed both strategies and defined the populations of patients for whom only one revascularization method would be effective.
SYNTAX, a prospective, clinical trial, was conducted at 85 sites in the United States and Europe, and enrolled 1800 patients with three-vessel or left main CAD to undergo CABG or PCI on a 1:1 ratio. For all patients, a local cardiac surgeon and interventional cardiologist determined that equivalent anatomical revascularization could be achieved with either treatment. All diagnostic angiograms were scored according to the SYNYAX score algorithm. The 12-month rates of major adverse cardiac or cerebrovascular events were analyzed on the basis of the SYNTAX score: a higher scores indicated a patient with a more complex coronary disease and a lower score was defined as less complex. The primary end point was a major adverse cardiac or cerebrovascular event (i.e. death from any cause, stroke, myocardial infarction, or repeat revascularization) during the 12 month period after randomization. If a patient could benefit only from one of the two treatments, he/she was entered into a parallel nested CABG or PCI registry. For the most part, clinical characteristics prior to surgery were similar in the two groups.

Rates of major adverse cardiac or cerebrovascular events at 12 months were significantly higher in the PCI group (13.5% vs. 5.9%, P<0.001); as a result, the criterion for noninferiority was not met. At 12 months, the rates of death and myocardial infarction were similar between the two groups, although stroke was significantly more likely to occur with CABG (2.2%, vs. 0.6% with PCI; P=0.003). The authors evaluated data resulting from the trial’s combined end point of major adverse cardiac or cerebrovascular events at one year and concluded that CABG should remain the standard of care for these patients.
The New England Journal of Medicine hosted a debate [2] about the clinical implications of the study’s findings and posed the following topic: what are the clinical implications of the study’s findings considering that the primary end point results showed PCI patients had more adverse events due to repeat revascularizations, but at 12 months, the rates of death and MI were similar between the two groups, and stroke was significantly more likely to occur with CABG (2.2% vs. 0.6% with PCI; P=0.003). What, then, should the standard of care be? Dr. Betsy Nabel, Director of the NHLBI, stressed that doctors must evaluate the results of the SYNTAX trial more thoroughly, and they should consider in greater detail the differences in the two groups of patients in subsequent studies, such as patient’s preference, complexity of coronary anatomy, medical state, comorbidities, and potential risks and benefits of each individual patient in making a decision about the best therapy for the patient.

[1] Serruys PW, Morice MC, Kappeteien P et al. Percutaneous coronary intervention versus coronary artery bypass grafting for severe coronary artery disease. N Engl J Med 2008;360:961-72

[2] Lee TH, Hillis LD, Nabel EG. CABG vs. stenting: clinical implications of the SYNTAX trial. http://www.nejm.org/perspective-roundtable/syntax-cabg-vs-stenting-trial/

Note: You may need subscriptions to access content from links on this page. You are responsible for obtaining these subscriptions.

* To view the online text from the book, please navigate to SpringerLink or use the DVD to access electronic content. SpringerLink is a subscription service. For further information, click here.

Further information: Aortic Valve Disease (see p381) from Cardiovascular Medicine, 3rd Edn*

In the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) trial [1], the clinical effects of long-term, intensive lipid-lowering therapy with daily use of simvastatin and ezetimibe were evaluated in patients with asymptomatic, mild-to-moderate aortic-valve (AV) stenosis, and no other indication for lipid-lowering treatment.

A patient total of 1873 underwent randomization at 173 study sites in seven European countries, with 944 patients assigned to 40 mg of simvastatin and 10 mg of ezetimibe daily and 929 patients assigned to placebo. The primary outcome was a composite of major cardiovascular events, including death from cardiovascular causes, AV replacement, nonfatal myocardial infarction (MI), hospitalization for unstable angina pectoris, heart failure, coronary-artery bypass grafting (CABG), percutaneous coronary intervention (PCI), and nonhemorrhagic stroke. Secondary outcomes were events related to AV stenosis and ischemic cardiovascular events.

At median follow-up of 52.2 weeks, the simvastatin-ezetimibe group recorded a primary composite outcome in 333 patients (35.3%) and a primary outcome was recorded in 355 patients (38.2%) in the placebo group (hazard ratio [HR] in the simvastatin-ezetimibe group, 0.96; 95% confidence interval [CI], 0.83–1.12; P=0.59). In 267 patients (28.3%) in the simvastatin-ezetimibe group, AV replacement was performed, and 278 patients (29.9%) had AV replacement in the placebo group (HR, 1.00; 95% CI, 0.84–1.18; P=0.97). Fewer patients had ischemic cardiovascular events in the simvastatin-ezetimibe group (148 patients) than in the placebo group (187 patients) (HR, 0.78; 95% CI, 0.63–97%; P=0.02), mainly because of the smaller number of patients who underwent CABG. Cancer occurred more frequently in the simvastatin-ezetimibe group (105 vs. 70, P=0.01).

The investigators concluded that simvastatin-ezetimibe did not reduce combined AV events and ischemic events in patients with aortic stenosis. Although the therapy reduced the incidence of ischemic cardiovascular events, they were not related to AV stenosis, and concern over the numbers of patients with new and fatal cancers indicates that the therapy requires further investigation.

[1] Rossebo AB, Pedersen TR, Boman K et al. Intensive lipid lowering with simvastatin and ezetimibe in aortic stenosis (SEAS). N Engl J Med 2008;359:1343-56

Note: You may need subscriptions to access content from links on this page. You are responsible for obtaining these subscriptions.

* To view the online text from the book, please navigate to SpringerLink or use the DVD to access electronic content. SpringerLink is a subscription service. For further information, click here.

Further information: Percutaneous Coronary Intervention for Acute Myocardial Infarction (see p1021) from Cardiovascular Medicine, 3rd Edn*

In an effort to reduce thrombotic complications for patients undergoing percutaneous coronary intervention (PCI) for coronary disease, a number of clinical trials have been conducted to investigate antithrombotic regimens. However, in addition to concern over thrombotic complications related to PCI, concerns regarding adverse consequences as a result of periprocedural bleeding indicate that those concerns must be considered as well when evaluating antithrombotic therapies. In the current study [1], investigators compared bivalirudin, a relatively new direct thrombin inhibitor, with unfractionated heparin in patients who had stable or unstable angina pectoris and who were undergoing stent placement PCI after pretreatment with 600 mg of clopidogrel.

Enrollment involved 4570 patients with stable or unstable angina, but who had normal levels of troponin T and creatine kinase MB and were to have PCI after pretreatment with a 600 mg dose of clopidogrel at least 2 hours before the procedure. Of those, 2289 patients were double-blinded and randomly assigned to receive bivalirudin and 2281 of them received unfractionated heparin. The primary endpoint was the composite of death, myocardial infarction (MI), urgent target-vessel revascularization due to myocardial ischemia within 30 days after randomization, or major bleeding during the index hospitalization. The secondary endpoint was the composite of death, MI, or urgent target-vessel revascularization.

In the bivalirudin group, the incidence of the primary endpoint was 8.3% or 190 patients, and in the unfractionated heparin group, it was 8.7% or 199 patients (relative risk [RR], 0.94; 95% confidence interval [CI], 0.77–1.15; P=0.57). The secondary endpoint occurred in 134 patients, or 5.9%, in the bivalirudin group and 115 patients, or 5.0%, in the unfractionated heparin group (RR. 1.16; 95% CI, 0.91–1.49; P=0.23). In the bivalirudin group, the incidence of bleeding was 3.1%, or 70 patients, and in the unfractionated heparin group, it was 4.6% or 104 patients (RR, 0.66; 95% CI, 0.49–0.90; P=0.008).
Results showed that although in patients undergoing PCI who had stable or unstable angina and no elevation of biomarkers, bivalirudin significantly reduced the incidence of bleeding, it did not provide a net clinical benefit compared with unfractionated heparin.

[1] Kastrati A, Neumann FJ, Mehilli J et al. Bivalirudin versus unfractionated heparin during percutaneous coronary intervention. N Engl J Med 2008;359:688-696.

Note: You may need subscriptions to access content from links on this page. You are responsible for obtaining these subscriptions.

* To view the online text from the book, please navigate to SpringerLink or use the DVD to access electronic content. SpringerLink is a subscription service. For further information, click here.

Further information: Endocrine Disorders of the Heart (see p2295) from Cardiovascular Medicine, 3rd Edn*
 
Patients originally studied in the United Kingdom Prospective Diabetes Study (UKPDS) were investigated for post-trial monitoring to determine whether risk reductions for microvascular and macrovascular disease, achieved with the use of improved blood-pressure control during the trial, were sustained [1]. The original trial was performed from 1987–1991, and 5102 patients with newly diagnosed type 2 diabetes mellitus who enrolled in the UKPDS trial were randomly assigned to tight blood-pressure control regimen involving an angiotensin-converting-enzyme (ACE) inhibitor or a beta-blocker, or a less-tight blood pressure control regimen that excluded these mediators.

In the group receiving tight control, there were relative risk reductions of 24% for any diabetes-related end point, 32% for diabetes-related death, 44% for stroke, and 37% for microvascular disease. After a 5-year follow-up, reports from data obtained from patients suggested that there may be a continuing effect of earlier improved management of risk factors. When the trial ended in 1991, patients entered a 10-year post-trial monitoring program, and information was obtained by clinic visits and questionnaires; by years 6–10, funding constraints resulted in the use of questionnaires only. The current paper reports the results of a 10-year, post-interventional follow-up of the survivor cohort of the UKPDS blood-pressure study using data obtained from the documentation of hospitals and general practitioners. The authors examined whether a continued benefit of earlier improved blood-pressure control was evident, and if there were continued benefit, the degree to which it continued.

The report concluded that the benefits of previously improved blood-presssure control were not sustained when blood pressure differences were no longer maintained. Optimal blood pressure control is of major importance in patients with type 2 diabetes and reduces the risks of microvascular and macrovascular disease, if blood-pressure control is maintained.

[1] Holman RR, Paul SK, Bethel A, et al. Long-term follow-up after tight control of blood pressure in type 2 diabetes. N Engl J Med 2008;359:1565-76

Note: You may need subscriptions to access content from links on this page. You are responsible for obtaining these subscriptions.

* To view the online text from the book, please navigate to SpringerLink or use the DVD to access electronic content. SpringerLink is a subscription service. For further information, click here.