Kevin M. Harris

Magnitude of Left Ventricular Hypertrophy and Risk of Sudden Death in Hypertrophic Cardiomyopathy

BACKGROUND Sudden death is known to be a possible consequence of hypertrophic cardiomyopathy. Quantification of the risk of sudden death, however, remains imprecise for most patients with this disease. METHODS We assessed the relation between the magnitude of left ventricular hypertrophy and mortality in 480 consecutive patients with hypertrophic cardiomyopathy. The patients were categorized into five subgroups according to maximal wall thickness: 15 mm or less, 16 to 19 mm, 20 to 24 mm, 25 to 29 mm, and 30 mm or more. Their ages ranged from 1 to 89 years (median, 47). RESULTS Over a mean follow-up period of 6.5 years, 65 of the 480 patients (14 percent) died: 23 suddenly, 15 of heart failure, and 27 of noncardiac causes or stroke. The risk of sudden death increased progressively and in direct relation to wall thickness (P=0.001), ranging from 0 per 1000 person-years (95 percent confidence interval, 0 to 14.4) for a wall thickness of 15 mm or less to 18.2 per 1000 person-years (95 percent confidence interval, 7.3 to 37.6) for a wall thickness of 30 mm or more and almost doubling from each wall-thickness subgroup to the next. The cumulative risk 20 years after the initial evaluation was close to zero for patients with a wall thickness of 19 mm or less but almost 40 percent for wall thicknesses of 30 mm or more. As compared with the other subgroups, patients with extreme hypertrophy were the youngest (mean age, 31 years), and most (41 of 43) had mild symptoms or no symptoms; of the 12 patients who were less than 18 years old at the initial evaluation, 5 died suddenly. CONCLUSIONS In hypertrophic cardiomyopathy, the magnitude of hypertrophy is directly related to the risk of sudden death and is a strong and independent predictor of prognosis. Young patients with extreme hypertrophy, even those with few or no symptoms, appear to be at substantial long-term risk and deserve consideration for interventions to prevent sudden death. The majority of patients with mild hypertrophy are at low risk and can be reassured regarding their prognosis.

Prevalence, Clinical Profile, and Significance of Left Ventricular Remodeling in the End-Stage Phase of Hypertrophic Cardiomyopathy

Background— End stage (ES) is a recognized part of the hypertrophic cardiomyopathy (HCM) disease spectrum. Frequency, clinical profile and course, and treatment strategies in these patients remain incompletely defined. Methods and Results— Three HCM cohorts comprised 1259 patients, including 44 (3.5%) characterized as ES with systolic dysfunction (ejection fraction <50% at rest; range 15% to 49%). ES developed at a wide age range (14 to 74 years), with 45% of patients ≤40 years old. Although 29 patients (66%) died of progressive heart failure, had sudden death events, or underwent heart transplantation, 15 (34%) survived with medical management over 3±3 years. Duration from onset of HCM symptoms to ES identification was considerable (14±10 years), but ES onset to death/transplantation was brief (2.7±2 years). ES occurred with similar frequency in patients with or without prior myectomy (P=0.84). Appropriate defibrillator interventions were 10% per year in patients awaiting donor hearts. Most ES patients (n=23; 52%) showed substantial left ventricular (LV) remodeling with cavity dilatation. Less complete remodeling occurred in 21 patients (48%), including 5 with persistence of a nondilated and markedly hypertrophied LV. Pathology and magnetic resonance imaging showed extensive (transmural) fibrosis in 9 of 11 ES patients. At initial evaluation, patients who developed ES were younger with more severe symptoms, had a larger LV cavity, and more frequently had a family history of ES than other HCM patients. Conclusions— ES of nonobstructive HCM has an expanded and more diverse clinical expression than previously appreciated, including occurrence in young patients, heterogeneous patterns of remodeling, frequent association with atrial fibrillation, and impaired LV contractility that precedes cavity dilatation, wall thinning, and heart failure symptoms. ES is an unfavorable complication (mortality rate 11% per year) and a sudden death risk factor; it requires vigilance to permit timely recognition and the necessity for defibrillator implantation and heart transplantation.

Can late survival of patients with moderate ischemic mitral regurgitation be impacted by intervention on the valve

BACKGROUND Ischemic mitral regurgitation is known to be associated with poor long-term outcome after coronary artery bypass grafting; however, our ability to alter that outcome with intervention on the valve is unclear. The decision to address the valve is most challenging for patients with only moderate mitral regurgitation, particularly with the popularization of off-pump surgery. We therefore reviewed early and late outcomes of patients undergoing revascularization with or without mitral valve surgery. METHODS Patients with moderate mitral regurgitation undergoing revascularization with and without mitral surgery between January 1991 and September 1996 were identified retrospectively. Operative notes were reviewed and patients with structural valve disease excluded. Perioperative events and late outcomes as determined by telephone contact and search of the social security death index (survival data 97% complete) were compared. RESULTS One hundred seventy-six patients with moderate mitral regurgitation underwent revascularization alone (n = 142) or with mitral repair or replacement (n = 34). Those undergoing revascularization alone had a higher serum creatinine, somewhat less mitral regurgitation, and lower New York Heart Association functional class preoperatively. Operative mortality was greater with valve surgery (21% vs 9%, p = 0.047). Actuarial survival of both groups at 5 years was similar (52% vs 58%, p = NS); however, when stratified by preoperative functional class, those with more advanced heart failure preoperatively had superior late survival if their mitral valve was intervened upon. CONCLUSIONS The late survival of patients with ischemic mitral regurgitation undergoing coronary revascularization remains poor; however, intervention on the mitral valve appears to benefit those with symptomatic heart failure.

Presentation, diagnosis, and outcomes of acute aortic dissection: 17-year trends from the international registry of acute aortic dissection

BACKGROUND Diagnosis, treatment, and outcomes of acute aortic dissection (AAS) are changing. OBJECTIVES This study examined 17-year trends in the presentation, diagnosis, and hospital outcomes of AAD from the International Registry of Acute Aortic Dissection (IRAD). METHODS Data from 4,428 patients enrolled at 28 IRAD centers between December 26, 1995, and February 6, 2013, were analyzed. Patients were divided according to enrollment date into 6 equal groups and by AAD type: A (n = 2,952) or B (n = 1,476). RESULTS There was no change in the presenting complaints of severe or worst-ever pain for type A and type B AAD (93% and 94%, respectively), nor in the incidence of chest pain (83% and 71%, respectively). Use of computed tomography (CT) for diagnosis of type A increased from 46% to 73% (p < 0.001). Surgical management for type A increased from 79% to 90% (p < 0.001). Endovascular management of type B increased from 7% to 31% (p < 0.001). Type A in-hospital mortality decreased significantly (31% to 22%; p < 0.001), as surgical mortality (25% to 18%; p = 0.003). There was no significant trend in in-hospital mortality in type B (from 12% to 14%). CONCLUSIONS Presenting symptoms and physical findings of AAD have not changed significantly. Use of chest CT increased for type A. More patients in both groups were managed with interventional procedures: surgery in type A and endovascular therapy in type B. A significant decrease in overall in-hospital mortality was seen for type A but not for type B.

Original InvestigationPresentation, Diagnosis, and Outcomes of Acute Aortic Dissection: 17-Year Trends From the International Registry of Acute Aortic Dissection

BACKGROUND Diagnosis, treatment, and outcomes of acute aortic dissection (AAS) are changing. OBJECTIVES This study examined 17-year trends in the presentation, diagnosis, and hospital outcomes of AAD from the International Registry of Acute Aortic Dissection (IRAD). METHODS Data from 4,428 patients enrolled at 28 IRAD centers between December 26, 1995, and February 6, 2013, were analyzed. Patients were divided according to enrollment date into 6 equal groups and by AAD type: A (n = 2,952) or B (n = 1,476). RESULTS There was no change in the presenting complaints of severe or worst-ever pain for type A and type B AAD (93% and 94%, respectively), nor in the incidence of chest pain (83% and 71%, respectively). Use of computed tomography (CT) for diagnosis of type A increased from 46% to 73% (p < 0.001). Surgical management for type A increased from 79% to 90% (p < 0.001). Endovascular management of type B increased from 7% to 31% (p < 0.001). Type A in-hospital mortality decreased significantly (31% to 22%; p < 0.001), as surgical mortality (25% to 18%; p = 0.003). There was no significant trend in in-hospital mortality in type B (from 12% to 14%). CONCLUSIONS Presenting symptoms and physical findings of AAD have not changed significantly. Use of chest CT increased for type A. More patients in both groups were managed with interventional procedures: surgery in type A and endovascular therapy in type B. A significant decrease in overall in-hospital mortality was seen for type A but not for type B.

Sensitivity of the Aortic Dissection Detection Risk Score, a Novel Guideline-Based Tool for Identification of Acute Aortic Dissection at Initial Presentation Results From the International Registry of Acute Aortic Dissection

Background— In 2010, the American Heart Association and American College of Cardiology released guidelines for the diagnosis and management of patients with thoracic aortic disease, which identified high-risk clinical features to assist in the early detection of acute aortic dissection. The sensitivity of these risk markers has not been validated. Methods and Results— We examined patients enrolled in the International Registry of Acute Aortic Dissection from 1996 to 2009. The number of patients with confirmed acute aortic dissection who presented with 1 or more of 12 proposed clinical risk markers was determined. An aortic dissection detection (ADD) risk score of 0 to 3 was calculated on the basis of the number of risk categories (high-risk predisposing conditions, high-risk pain features, high-risk examination features) in which patients met criteria. The ADD risk score was tested for sensitivity. Of 2538 patients with acute aortic dissection, 2430 (95.7%) were identified by 1 or more of 12 proposed clinical risk markers. With the use of the ADD risk score, 108 patients (4.3%) were identified as low risk (ADD score 0), 927 patients (36.5%) were intermediate risk (ADD score 1), and 1503 patients (59.2%) were high risk (ADD score 2 or 3). Among 108 patients with no clinical risk markers present (ADD score 0), 72 had chest x-rays recorded, of which 35 (48.6%) demonstrated a widened mediastinum. Conclusions— The clinical risk markers proposed in the 2010 thoracic aortic disease guidelines and their application as part of the ADD risk score comprise a highly sensitive clinical tool for the detection of acute aortic dissection.

Transesophageal echocardiographic and clinical features of aortic intramural hematoma

OBJECTIVE This study sought to determine the transesophageal echocardiographic features and natural history of patients with aortic intramural hematoma. METHODS The transesophageal echocardiograms of all patients who had symptoms indicative of aortic dissection over 6 years were reviewed. Measurements were made of the involved aortic segment in the study patients, and follow-up was obtained. RESULTS In patients with aortic intramural hematoma, the wall thickness of the involved segment was significantly greater for descending segments than ascending segments (ascending aorta 7 +/- 2 mm, descending aorta 15 +/- 6 mm, p = 0.0016). In each case, the crescent-shaped intramural hematoma involved one wall predominantly, leading to compression of the aortic lumen. The findings of echolucent areas and displaced intimal calcium were found in the majority of patients. Four of eight patients with intramural hematoma of the ascending aorta were treated medically and four were treated surgically. The 30-day mortality was 50% in the medically treated patients and 0% in the surgically treated group. Four of 11 patients with isolated intramural hematoma of the descending aorta were treated medically and seven were treated surgically. All medically treated and 86% of surgically treated patients were alive at 30 days. CONCLUSIONS Aortic intramural hematoma has distinct and identifiable transesophageal echocardiographic features. These data support those of previous studies documenting high morbidity and mortality in patients with aortic intramural hematoma.

Effects of obstruction on renal functions

Following ureteral obstruction there is a progressive fall in glomerular filtration rate (GFR) due to a reduction in single nephron glomerular filtration rate (SNGFR) and a reduced number of filtering nephrons. Renal plasma flow also declines after a transient, prostaglandin-dependent increase, due to afferent and efferent arteriolar vasoconstriction. The vasoactive hormones thromboxane A2 and angiotensin II are implicated in the pathogenesis of the vasoconstriction following ureteral obstruction and they also reduce the glomerular ultrafiltration coefficient by causing mesangial contraction. Ureteral obstruction also leads to profound changes in renal tubular cell function. These include altered sodium and water handling resulting in a post-obstructive diuresis and natriuresis and a failure to dilute or concentrate the urine. Potassium and divalent cation exchange is also affected, as is urinary acidification. Furthermore, the response of the tubule to hormones such as antidiuretic hormone and parathyroid hormone is impaired. The pathophysiology of these alterations in renal function is discussed.

Type-selective benefits of medications in treatment of acute aortic dissection (from the International Registry of Acute Aortic Dissection [IRAD]).

The effects of medications on the outcome of aortic dissection remain poorly understood. We sought to address this by analyzing the International Registry of Acute Aortic Dissection (IRAD) global registry database. A total of 1,301 patients with acute aortic dissection (722 with type A and 579 with type B) with information on their medications at discharge and followed for ≤5 years were analyzed for the effects of the medications on mortality. The initial univariate analysis showed that use of β blockers was associated with improved survival in all patients (p = 0.03), in patients with type A overall (p = 0.02), and in patients with type A who received surgery (p = 0.006). The analysis also showed that use of calcium channel blockers was associated with improved survival in patients with type B overall (p = 0.02) and in patients with type B receiving medical management (p = 0.03). Multivariate models also showed that the use of β blockers was associated with improved survival in those with type A undergoing surgery (odds ratio 0.47, 95% confidence interval 0.25 to 0.90, p = 0.02) and the use of calcium channel blockers was associated with improved survival in patients with type B medically treated patients (odds ratio 0.55, 95% confidence interval 0.35 to 0.88, p = 0.01). In conclusion, the present study showed that use of β blockers was associated with improved outcome in all patients and in type A patients (overall as well as in those managed surgically). In contrast, use of calcium channel blockers was associated with improved survival selectively in those with type B (overall and in those treated medically). The use of angiotensin-converting enzyme inhibitors did not show association with mortality.

The IRAD Classification System for Characterizing Survival after Aortic Dissection

BACKGROUND The classification of aortic dissection into acute (<14 days from symptom onset) versus chronic (≥14 days) is based on survival estimates of patients treated decades before modern diagnostic and treatment modalities were available. A new classification of aortic dissection in the current era may provide clinicians with a more precise method of characterizing the interaction of time, dissection location, and treatment type with survival. METHODS We developed separate Kaplan-Meier survival curves for Type A and Type B aortic dissection using data from the International Registry of Aortic Dissection (IRAD). Daily survival was stratified based on type of therapy provided: medical therapy alone (medical), nonsurgical intervention plus medical therapy (endovascular), and open surgery plus medical therapy (surgical). The log-rank statistic was used to compare the survival curves of each management type within Type A and Type B aortic dissection. RESULTS There were 1815 patients included, 67.3% male with mean age 62.0 ± 14.2 years. When survival curves were constructed, 4 distinct time periods were noted: hyperacute (symptom onset to 24 hours), acute (2-7 days), subacute (8-30 days), and chronic (>30 days). Overall survival was progressively lower through the 4 time periods. CONCLUSIONS This IRAD classification system can provide clinicians with a more robust method of characterizing survival after aortic dissection over time than previous methods. This system will be useful for treating patients, counseling patients and families, and studying new diagnostic and treatment methods.