Atypical Takotsubo Cardiomyopathy with Hypokinetic Left Mid-ventricle and Apical Wall Sparing: A Case Report and Literature Review.

BACKGROUND: Takotsubo Cardiomyopathy (TTC) is an uncommon cause of acute reversible ventricular systolic dysfunction in the absence of obstructive Coronary Artery Disease (CAD). Typically manifesting as apical wall ballooning, TTC can rarely present atypically with apical wall sparing. CASE REPORT: A 62-year-old female presented with complaints of chest pain and features mimicking acute coronary syndrome. Coronary angiogram revealed no obstructive CAD and left ventriculogram showed reduced ejection fraction, normal left ventricular apex and hypokinetic mid-ventricles consistent with atypical TTC. The patient was discharged home on heart failure medications and a follow-up transthoracic echocardiogram demonstrated improved left ventricular function with no wall motion abnormality. CONCLUSION: This case report provides an insight into the diagnosis and management of TTC in the absence of pathognomic features.

Combined use of direct renin inhibitor and carvedilol in heart failure with preserved systolic function.

HYPOTHESES: Heart failure with preserved systolic function (HFPSF) has attained epidemic proportions; however evidence-based therapeutic interventions have not advanced despite continued research over the past three decades. We propose the combined use of direct renin inhibitor and carvedilol for this condition. RATIONALE: The Renin Angiotensin Aldosterone System (RAAS) plays a central role in myocyte hypertrophy, fibrosis and ventricular remodeling which is responsible for the diastolic dysfunction in HFPSF. Rising serum aldosterone levels with age have been implicated as a cause of myocardial fibrosis in the elderly. The sole use of Angiotensin Converting Enzyme Inhibitors or Angiotensin Receptor Blockers is associated with angiotensin-II and aldosterone escape and increased plasma renin activity. Carvedilol is a novel third generation non-selective ß-blocker. The use of combination therapy will facilitate in better blood pressure control, reduce afterload, improve ventricular relaxation, cause regression of ventricular remodeling/fibrosis, maintain atrioventricular synchrony and enhance cardio-metabolic profile. The individual benefits of direct renin inhibitor and carvedilol could plausibly have a supra-additive effect when used in combination. Besides this, carvedilol can further reduce generation of free radicals, decrease LDL oxidation, improve Doppler echo diastolic parameters and decrease cardiac norepinephrine and density of cardiac ß-receptors. CONCLUSION: Evidence suggests that patients with HFPSF are treated less aggressively as compared to patients with heart failure with systolic dysfunction. Aggressive therapy with concurrent use of direct renin inhibitor and carvedilol will help in improving outcomes in this vulnerable patient sub-population. No prior trial has evaluated the combined use of these drugs for the treatment of HFPSF.

Comparison of mortality and morbidity in patients with atrial fibrillation and heart failure with preserved versus decreased left ventricular ejection fraction.

Almost 50% of patients with congestive heart failure (HF) have preserved ejection fraction (PEF). Data on the effect of HF-PEF on atrial fibrillation outcomes are lacking. We assessed the prognostic significance of HF-PEF in an atrial fibrillation population compared to a systolic heart failure (SHF) population. A post hoc analysis of the National Heart, Lung, and Blood Institute-limited access data set of the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) trial was carried out. The patients with a history of congestive HF and a preserved ejection fraction (EF >50%) were classified as having HF-PEF (n = 320). The patients with congestive HF and a qualitatively depressed EF (EF <50%) were classified as having SHF (n = 402). Cox proportional hazards analysis was performed. The mean follow-up duration was 1,181 ± 534 days/patient. The patients with HF-PEF had lower all-cause mortality (hazard ratio [HR] 0.62, 95% confidence interval [CI] 0.46 to 0.85, p = 0.003) and cardiovascular mortality (HR 0.56, 95% CI 0.38 to 0.84, p = 0.006), with a possible decreased arrhythmic end point (HR 0.39, 95% CI 0.16 to 1.006, p = 0.052) than did the patients with SHF. No differences were observed for ischemic stroke (HR 1.08, 95% CI 0.48 to 2.39, p = 0.86), rehospitalization (HR 0.89, 95% CI 0.75 to 1.07, p = 0.24), or progression to New York Heart Association class III-IV (odds ratio 0.80, 95% CI 0.42 to 1.54, p = 0.522). In conclusion, although patients with HF-PEF have better mortality outcomes than those with SHF, the morbidity appears to be similar.

Prevalence, determinants, and clinical significance of cardiac troponin-I elevation in individuals admitted for a hypertensive emergency.

Hypertensive emergencies (HEs) are frequently accompanied with the release of cardiac troponin I (cTnI); however, determinants and clinical significance of cTnI elevation are largely unknown. A retrospective analysis was performed on patients (n = 567) with a diagnosis of HE admitted to two tertiary care centers that primarily serve an inner-city population. Data on demographics, clinical variables, and cTnI were collected through chart review. Using regression analyses, predictors of cTnI elevation were studied and the impact of cTnI on all-cause mortality (data obtained through the Social Security Death Index) was determined. cTnI elevation was observed in 186 (32.3%) admissions with a mean peak cTnI level of 4.06 ± 14.6 ng/mL. Predictors of cTnI were age, history of hypercholesterolemia, blood urea nitrogen level, pulmonary edema, and requirement for mechanical ventilation. During a mean follow-up period of 3.1 years, there were 211 deaths (37%). Neither the presence nor the extent of cTnI elevation was associated with mortality, while age, history of coronary artery disease, and blood urea nitrogen level were predictive of mortality. cTnI elevation commonly occurs in the setting of HEs. Despite a high incidence of adverse clinical outcomes, cTnI elevation was not an independent predictor of mortality in this population.

Outcomes and risk prediction model for peripheral arterial disease in patients with stable coronary artery disease.

We used the National Heart, Lung, and Blood Institute Limited Access Dataset of Prevention of Events with Angiotensin-Converting Enzyme Inhibition (PEACE) Trial (n = 8290) which included patients with stable coronary artery disease (CAD) and preserved ejection fraction (>40%). We identified risk factors for the development of critical peripheral arterial disease (PAD; those needing angioplasty, bypass grafting, or aneurysm repair) and formulated a risk score by multivariate analyses. A total of 220 patients (2.8%) developed critical PAD over a mean follow-up of 4.7 years. Significant predictors of critical PAD were history of intermittent claudication, smoking, hypertension (HTN), coronary-artery bypass grafting (CABG), diabetes, age, serum cholesterol, and body mass index (BMI). Incident critical PAD was associated with increased composite outcome of cardiovascular death, myocardial infarction, percutaneous transluminal coronary angioplasty, or CABG (hazard ratio 1.82, 95% CI 1.50-2.22, P < .001). Risk assessment using our score may identify CAD patients at risk for critical PAD events.

Preserved or slightly depressed ejection fraction and outcomes after myocardial infarction.

BACKGROUND Left ventricular ejection fraction (EF) in post-myocardial infarction (MI) patients is a strong predictor of adverse cardiovascular events. Although resting EF as measured by transthoracic echocardiography (TTE), contrast ventriculography (CNV), and radionuclide angiography (RNA) exhibit high correlation, there is only modest agreement between these modalities. This study sought to explore whether modality of EF assessment influences prognostication of post-MI patients with normal or slightly reduced EF. METHODS AND RESULTS The National Heart, Lung, and Blood Institute (NHLBI) limited access dataset of the Prevention of Events with Angiotensin Converting Enzyme Inhibition (PEACE) Trial (1996-2003, n=8290) comparing trandolapril versus placebo was used. The cohort was partitioned into TTE (n=2582), RNA (n=816), and CNV (n=1155) groups based on modality of EF assessment. EF was a significant predictor of cardiovascular mortality (HR 0.97, 95% CI 0.95 to 0.98; p<0.005) and all cause mortality (HR 0.98, 95% CI 0.97 to 0.99; p=0.0002) on multivariate analysis in this population with preserved or mildly depressed EF. Although CNV, TTE, and RNA groups differed significantly in terms of baseline variables, no appreciable differences were noted between RNA (HR 1.13, 95% CI 0.85 to 1.50; ns) and CNV (HR 1.13, 95% CI 0.99 to 1.27; ns) groups, compared with TTE for all cause mortality. Similarly, no significant differences were observed for cardiovascular mortality between RNA (HR 1.23, 95% CI 0.82 to 1.84; p=0.31) and CNV (HR 1.14, 95% CI 0.78 to 1.67, p=0.49) versus TTE. CONCLUSION EF is a significant predictor of all-cause mortality and cardiovascular mortality in patients with preserved or mildly depressed EF. Modalities of EF measurement are interchangeable and do not play a significant role in prognostication in a post-MI population.

Renal disease and cardiac mortality in survivors of sudden cardiac death.

OBJECTIVE: Renal disease is associated with increased all-cause mortality and cardiovascular mortality. However, the role of ICD implantation on cardiac mortality in patients with renal disease has not been well studied. Implantable cardioverter-defibrillator (ICD) implantation is protective against cardiac death in a secondary prevention population with renal disease. METHODS: The Antiarrhythmics Versus Implantable Cardioverter Defibrillators (AVID) Trial (n = 1016) was a multicentre trial comparing ICD (n = 507) and anti-arrhythmic drugs (AAD) (n = 509) for secondary prevention of life-threatening ventricular tachyarrhythmias. We performed a post-hoc analysis of the AVID trial using the National Heart, Lung, and Blood Institute limited access dataset. Individuals in the original AVID study with history of renal disease (n = 82) were included in this analysis. Outcomes of our analysis were cardiac death and all-cause mortality. RESULTS: 41 patients had renal disease in both the ICD and AAD arms. A total of 116 patients died in the ICD arm, while 162 died in the AAD arm. Renal disease was an independent predictor (HR, 95% CI) of cardiac death (1.967, 1.09-3.57, P = 0.02) and all-cause mortality (2.04, 1.23-3.39, P = 0.01) in the AAD arm. Renal disease was also a predictor of all-cause mortality in the ICD arm (1.75, 1.01-3.01, P = 0.04). However, renal disease did not influence cardiac death in the ICD arm. CONCLUSIONS: Our study investigates the effect of ICD implantation in an entirely secondary prevention population with renal disease. ICD implantation appears to be equally protective against cardiac death in renal disease when compared to AAD.

Influence of obesity on outcomes in atrial fibrillation: yet another obesity paradox.

BACKGROUND: Obese patients have favorable outcomes in congestive heart failure, hypertension, peripheral vascular disease, and coronary artery disease. Obesity also has been linked with increased incidence of atrial fibrillation, but its influence on outcomes in atrial fibrillation patients has not been investigated. The objective of this research is to investigate the effect of obesity on outcomes in atrial fibrillation. METHODS: The Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study was one of the largest multicenter trials of atrial fibrillation, with 4060 patients. Subjects were randomized to rate versus rhythm-control strategy. We performed a post hoc analysis of the National Heart, Lung and Blood Institute limited access dataset of atrial fibrillation patients who had body mass index (BMI) data available in the AFFIRM study. BMI data were not available on 1542 patients. Patients with BMI >or=18.5 were split into normal (18.5-25), overweight (25-30), and obese (>30) categories as per BMI (kg/m(2)). Multivariate Cox proportional hazards regression was used on the eligible 2492 patients. End points were all-cause mortality and cardiovascular mortality. RESULTS: Over three fourths of all patients in our cohort were overweight or obese. There were 304 deaths (103 among normal weight, 108 among overweight, and 93 among obese) and 148 cardiovascular deaths (54 among normal weight, 41 among overweight, and 53 among obese) over a mean period of 3 years of patient follow-up. On multivariate analysis, overweight (hazard ratio [HR] 0.64; 95% confidence interval [CI], 0.48-0.84; P=.001) and obese (HR 0.80; 95% CI, 0.68-0.93; P=.005) categories were associated with lower all-cause mortality as compared with normal weight. Overweight (HR 0.40; 95% CI, 0.26-0.60; P <.001) and obese patients (HR 0.77; 95% CI, 0.62-0.95; P=.01) also had lower cardiovascular mortality as compared with the normal weight patients. CONCLUSIONS: Although in prior studies, obesity has been associated with increased risk of atrial fibrillation, an obesity paradox exists for outcomes in atrial fibrillation. Obese patients with atrial fibrillation appear to have better long-term outcomes than nonobese patients.

Epileptic patients who survived sudden cardiac death have increased risk of recurrent arrhythmias and death.

BACKGROUND: Cardiac arrhythmogenesis and cryptogenic epilepsy can be due to ion channel dysfunction and may coexist in the same patient. Sudden unexplained death in epilepsy (SUDEP) is a known entity with unknown cause, with the possibility of ventricular tachyarrhythmias being one of the causes. However, no prior study has investigated epileptic survivors of sudden cardiac death (SCD), recurrent life-threatening ventricular tachyarrhythmia (LTVA) and other outcomes in this patient population. METHODS: The Antiarrhythmics Versus Implantable Cardioverter Defibrillators (AVID) Trial (n = 1016) was a multicenter trial comparing a cardioverter-defibrillator device (ICD) (n = 507) and anti-arrhythmic drugs (AADs) (n = 499) for secondary prevention of LTVAs. Mean follow-up duration was 916 ± 471 days per patient. Patients with a history of epilepsy (n = 6) in the ICD arm were included in this analysis. End points were recurrence of LTVA, cardiac death and all-cause mortality. RESULTS: History of epilepsy (n = 6) was a significant predictor of recurrent LTVA [hazard ratio 3.53, 95% confidence interval (CI) 1.30-9.56], cardiac death (hazard ratio 4.14, 95% CI 1.30-13.14) and all-cause mortality (hazard ratio 3.82, 95% CI 1.40-10.48) in the ICD arm (n = 498). This relationship remained unchanged on multivariate analysis after controlling for baseline clinical differences. CONCLUSION: This is the first study to investigate the effect of epilepsy on secondary prevention of LTVA. Epileptic survivors of SCD are at significantly greater risk of recurrent arrhythmias and death as compared to other survivors of recurrent LTVA. Role of coexisting channelopathies in both epilepsy and arrhythmogenesis may explain SUDEP and requires further investigation.

Impact of lipid-lowering therapy on outcomes in atrial fibrillation.

Lipid-lowering therapy (LLT) decreases mortality in select patient populations. LLT has also been shown to have antiarrhythmic effects, thus favorably influencing the incidence and recurrence of atrial fibrillation (AF). However, data are lacking regarding the effect of LLT on mortality in patients with AF. The Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study was the one of the largest multicenter trials comprising of 4,060 patients with AF at high risk for stroke and death. This is a post hoc analysis of the National Heart, Lung, and Blood Institute limited-access dataset of AFFIRM patients who were on LLT at the time of randomization (n = 913). The control group consisted of AFFIRM patients who were not on LLT (n = 3,147). Cox proportional hazards analysis was performed controlling for baseline differences. The end point was all-cause mortality, cardiovascular mortality, and ischemic stroke. A separate analysis was carried out for the combined end point of death, ventricular tachycardia, ventricular fibrillation, cardiac arrest, ischemic stroke, major bleeding, systemic embolism, pulmonary embolism, and myocardial infarction. Patients on LLT were younger and on more cardioactive medications but also had more cardiovascular morbidities. On multivariate analysis, LLT use was associated with lower all-cause mortality (hazard ratio [HR] 0.77, 95% confidence interval [CI] 0.62 to 0.95, p = 0.01), cardiovascular mortality (HR 0.71, 95% CI 0.53 to 0.95, p = 0.02), ischemic stroke (HR 0.56, 95% CI 0.36 to 0.89, p = 0.01), and combined end point (HR 0.81, 95% CI 0.69 to 0.96, p = 0.01). In conclusion, a decrease in mortality and adverse cardiovascular events was observed using LLT in AF.

Valvular perforation in left-sided native valve infective endocarditis.

BACKGROUND: Left-sided native valve infective endocarditis (LNVIE) can result in mitral (MP) and aortic (AP) valve perforation, the prognostic significance of which remains poorly defined. HYPOTHESIS: Valvular perforation is associated with worse outcomes. METHODS: Retrospective review of patients with LNVIE during 1998-2005 was performed to examine characteristics and outcome predictors of LNVIE complicated by valve perforation. Patients were stratified as: group A: MP or AP detected by transesophageal echocardiography (TEE) or surgery; group B: no TEE evidence of MP or AP. RESULTS: A total of 123 patients were included (group A = 47, group B = 76). In group A, 35 patients (74.5%) had MP alone, 11 (23.4%) had AP alone, and 1 patient had both. Severe valvular insufficiency was encountered more in group A (85.1% versus 59.2%, p = 0.003), so was hemodialysis (40.4% versus 17.1%, p = 0.004) and indications for valvular surgery (93.6% versus 77.6%, p = 0.02). Group A had a higher rate of in-hospital death (31.9% versus 15.8%, p = 0.04). Among patients who had an indication for valvular surgery, the in-hospital mortality rate for those who underwent valvular surgery was 16.7% in group A, and 7.9% in group B (p = 0.4), compared to those who did not undergo surgery (71.4% versus 33.3%, p = 0.04). Amongst survivors, hospital stay was on average 9.2 d longer in group A (38.9 versus 29.7 d, p = 0.05). Univariate analysis revealed association between lower survival and valvular perforation (odds ratio [OR]: 0.4, 95% confidence interval [CI]: 0.17-0.95), that was lost after adjusting for hemodialysis. CONCLUSIONS: Valve perforation complicating LNVIE is associated with hemodialysis, severe valvular insufficiency, and significant morbidity and mortality. Compared to conservative management, early surgical intervention is associated with improved survival.

Relation of heart rate with cardiovascular disease in normal-weight individuals: the Chicago Heart Association Detection Project in Industry.

The authors investigated the association of resting heart rate (RHR) with cardiovascular disease (CVD) risk factors and mortality among normal-weight individuals. Using data from our cohort (baseline examination in 1967-1973), individuals with a body mass index of 18.5 to 24.9 kg/m(2) (men [n=3724] and women [n=4929] aged 18-39; men [n=1959] and women [n=3735] aged 40-59), were grouped by RHR: <75, 75-84, and > or =85 beats per minute (bpm). A lower RHR was associated with lower mean blood pressure (BP) and cigarette use in each subgroup and total cholesterol (TC) and diabetes in men (P<.05). After a 32-year follow-up, hazard ratios (95% confidence intervals) for CVD mortality for an RHR <75 compared with > or =85 bpm adjusted for age, race, education level, BP, cigarette use, diabetes, and TC were 0.58 (0.34-0.84), 0.73(0.56-0.95), and 0.77 (0.61-0.98) for men aged 18 to 39 and men and women aged 40 to 59, respectively. In women aged 18 to 39, the relationship was not significant. In general, normal-weight individuals with lower RHRs have lower levels of CVD risk factors and mortality.

Associations of psychosocial factors with heart rate and its short-term variability: multi-ethnic study of atherosclerosis.

OBJECTIVE: To examine the association of psychosocial factors with heart rate (HR) and its variability across multiple ethnic groups and by gender. Increased HR and reduced HR variability are markers of increased cardiovascular risk. METHODS: Between 2000 and 2002, 6814 men and women (2624 Whites, 1895 African-Americans, 1492 Hispanics, and 803 Chinese) aged 45 to 84 years took part in the first examination of the Multi-Ethnic Study of Atherosclerosis. Associations of psychosocial variables with mean values of HR and its short-term variability were tested, using multivariate regression models. RESULTS: In age, gender, race/ethnicity, and risk factor-adjusted analyses, a depressive symptom score was positively associated with HR and inversely associated with HR variability (standard deviation of normal-to-normal (N-N) interbeat intervals (SDNN) and the root mean square of successive differences in N-N intervals (RMSSD)). The adjusted mean differences per 1-SD (8 points) increment of depression score for HR, RMSSD, and SDNN were 0.5 (95% confidence interval (CI), 0.2-0.7), -0.8 (95% CI, -1.5 to -0.2), and -0.7 (95% CI, -1.1 to -0.2). The social support score was inversely associated with HR, but nonsignificantly associated with RMSSD and SDNN. There was no association of trait anger or trait anxiety with HR, RMSSD, or SDNN. Associations were generally consistent in men and women. CONCLUSIONS: These findings generally support the hypothesis that depression may be associated with increased HR and reduced HR variability, which increase the risk of cardiovascular diseases.

The association of heart rate recovery immediately after exercise with coronary artery calcium: the coronary artery risk development in young adults study.

We tested whether slower heart rate recovery (HRR) following graded exercise treadmill testing (GXT) was associated with the presence of coronary artery calcium (CAC). Participants (n = 2,648) ages 18-30 years at baseline examination underwent GXT, followed by CAC screening 15 years later. Slow HRR was not associated with higher odds of testing positive (yes/no) for CAC at year 15 (OR = 0.99, p = 0.91 per standard deviation change in HRR). Slow HRR in young adulthood is not associated with the presence of CAC at middle age.

The temporal relationship between heart rate recovery immediately after exercise and the metabolic syndrome: the CARDIA study.

AIMS: Slower heart rate recovery (HRR) following exercise is associated with the metabolic syndrome, yet the temporal relationship between the two remains unknown. We investigated the cross-sectional and longitudinal associations of slower HRR following a graded exercise treadmill test (GXT) with metabolic syndrome components and LDL-C. METHODS AND RESULTS: Participants aged 18-30 from the Coronary Artery Risk Development in Young Adults study underwent a symptom-limited maximal GXT at baseline (n = 4319) and 7 years later. HRR was calculated as the difference between maximum heart rate (HR) and HR 2 min after test cessation. Slower baseline HRR was associated with a higher cross-sectional level but not longitudinal (15 year follow-up) increases in blood pressure, triglyceride, waist circumference, and LDL-C. No cross-sectional or longitudinal association was observed between HRR and HDL-C. In contrast, participants with one or two or more metabolic syndrome components (National Cholesterol Education Program III and American Diabetes Association criterion) at baseline examination had significantly larger longitudinal declines in HRR [-3.48 (P < 0.05) and-5.64 bpm (P < 0.001), respectively] from baseline to year 7, when compared with participants without syndrome components (-2.40 bpm). CONCLUSION: Slower HRR does not precede development of the metabolic syndrome, but appears after syndrome components are present.