trandolapril and Arrhythmias--Cardiac

Cardiac failure is a disease which involves three different mechanisms: (1) the limits and imperfections of the general process of myocardial adaptation to mechanical stress, which includes various changes in genetic expression, including an increased collagen mass, but an unchanged collagen concentration; (2) the limits and imperfections of the adaptational process at the peripheral level which allows the entire organism to adapt to the low cardiac output; (3) fibrosis, an augmented collagen concentration, which is not a direct consequence of mechanical overload, but depends on aging, myocardial ischemia or hormonal changes. Middle-aged spontaneously hypertensive rats (SHRs) represent a good model of the common clinical situation. Three-month treatment with a CEI reduces, in parallel, arterial hypertension, left ventricular hypertrophy and ventricular fibrosis. Holter monitoring was also performed in these animals. Untreated SHRs when compared to age-matched Wistar rats have an increased number of ventricular premature beats which are suppressed by the treatment. In addition, heart rate variability has been quantified by using the pseudo Wigner-Villé transformation, a time and frequency domain method. The low frequency oscillations are hampered in SHRs. CEI normalizes this parameter.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Arrhythmias, Cardiac; Cardiomegaly; Collagen; Heart Rate; Indoles; Male; Rats; Rats, Inbred SHR; Rats, Wistar

Cardiac hypertrophy due to a chronic mechanical overload puts into play a biologic cascade, including a trigger (the mechanical stretch), a transmitter (very likely to be the phosphoinositol pathway), and the final target (which is the DNA). The permanent changes in genetic expression resulting from the activation of this cascade allows the heart to produce normal active tension at a lower cost in terms of energy expenditure. The process is reversible, providing the treatment reduces the real load on the heart--i.e., not only the peripheral resistances but also the aortic impedance--during a period of time that has to be several times the half-life of cardiac proteins, and also that the treatment has an effect on the detrimental consequences of cardiac hypertrophy, namely, the systolic and diastolic dysfunction and the incidence of arrhythmias. In this report semisenescent spontaneously hypertensive rats were treated for 3 months with the converting enzyme inhibitor trandolapril. The treatment had a rather modest effect on blood pressure but resulted in a pronounced reduction in cardiac hypertrophy and in cardiac fibrosis, an improved coronary reserve, and attenuated both the effects of anoxia on the left ventricular diastolic compliance and the incidence of ventricular arrhythmias.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Arrhythmias, Cardiac; Humans; Hypertrophy, Left Ventricular; Hypoxia; Indoles; Male; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Ventricular Function, Left

To determine the relationship between resting heart rate (RHR) and adverse outcomes in coronary artery disease (CAD) patients treated for hypertension with different RHR-lowering strategies.. Time to adverse outcomes (death, non-fatal myocardial infarction, or non-fatal-stroke) and predictive values of baseline and follow-up RHR were assessed in INternational VErapamil-SR/trandolapril STudy (INVEST) patients randomized to either a verapamil-SR (Ve) or atenolol (At)-based strategy. Higher baseline and follow-up RHR were associated with increased adverse outcome risks, with a linear relationship for baseline RHR and J-shaped relationship for follow-up RHR. Although follow-up RHR was independently associated with adverse outcomes, it added less excess risk than baseline conditions such as heart failure and diabetes. The At strategy reduced RHR more than Ve (at 24 months, 69.2 vs. 72.8 beats/min; P < 0.001), yet adverse outcomes were similar [Ve 9.67% (rate 35/1000 patient-years) vs. At 9.88% (rate 36/1000 patient-years, confidence interval 0.90-1.06, P = 0.62)]. For the same RHR, men had a higher risk than women.. Among CAD patients with hypertension, RHR predicts adverse outcomes, and on-treatment RHR is more predictive than baseline RHR. A Ve strategy is less effective than an At strategy for lowering RHR but has a similar effect on adverse outcomes.

Topics: Aged; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Female; Heart Rate; Humans; Hypertension; Indoles; Male; Treatment Outcome; Verapamil

The long-term prognostic importance of hyperkinesia is unknown following an acute myocardial infarction (AMI). The American Society of Echocardiography recommends that hyperkinesia should not be included in calculation of wall motion index (WMI). The objective of the present study was to determine if hyperkinesia should be included in WMI when it is estimated for prognostic purposes following an AMI. Six thousand, six hundred seventy-six consecutive patients were screened 1 to 6 days after AMI in 27 Danish hospitals. WMI was measured in 6,232 patients applying the 9-segment model and the following scoring system: 3 for hyperkinesia, 2 for normokinesia, 1 for hypokinesia, 0 for akinesia, and -1 for dyskinesia. All patients were followed with respect to mortality for at least 3 years. WMI was calculated in 2 different ways: 1 including hyperkinetic segments (hyperkinetic-WMI) and the other excluding nonhyperkinetic segments (nonhyperkinetic-WMI) by converting the hyperkinetic segments to normokinetic segments. Hyperkinesia occurred in 736 patients (11.8%). WMI was an important prognostic factor (relative risk 2.49; p = 0.0001) for long-term mortality together with heart failure, history of hypertension, angina, or diabetes, previous AMI, age, thrombolytic therapy, arrhythmias, and bundle branch block. In a multivariate analysis including nonhyperkinetic-WMI, hyperkinesia was associated with a relative risk of 0.84, which was statistically significant (confidence intervals 0.74 to 0.96; p = 0.01). When hyperkinesia was included, both in WMI (hyperkinetic-WMI) and as an independent variable, no additional prognostic information (relative risk 0.93; p = 0.26) was obtained. An echocardiographic evaluation shortly after an AMI gave important prognostic information, especially if the information concerning hyperkinesia was included. If WMI is used for prognostic purposes, hyperkinesia should be included in calculation of the index.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Angina Pectoris; Angiotensin-Converting Enzyme Inhibitors; Arrhythmias, Cardiac; Bundle-Branch Block; Cardiac Output, Low; Confidence Intervals; Diabetes Complications; Echocardiography; Female; Follow-Up Studies; Humans; Hypertension; Indoles; Longitudinal Studies; Male; Middle Aged; Multivariate Analysis; Myocardial Contraction; Myocardial Infarction; Prognosis; Risk Factors; Survival Rate; Thrombolytic Therapy; Ventricular Dysfunction, Left