Hypertrophic Cardiomyopathy: From Medical Treatment to Advanced Heart Failure Therapies.

PURPOSE OF REVIEW: There has been much debate surrounding novel medical therapies and heart transplantation listing challenges in patients with hypertrophic cardiomyopathy (HCM). RECENT FINDINGS: Recent clinical trials led to FDA approval of mavacamten (a cardiac myosin inhibitor), offering symptom relief and potentially delaying/avoiding invasive septal reduction therapies for some patients with HCM and left ventricular outflow obstruction (LVOTO). For those with refractory symptoms and end-stage heart failure, heart transplantation remains the gold standard. However, the concern for the organ allocation system failing to prioritize those individuals persists. HCM is a heterogeneous genetic condition with variable penetration and clinical presentation. Even though a large portion of patients remain asymptomatic, an important minority develops debilitating symptoms refractory to medical therapy. Post-HT short- and long-term outcomes are favorable. However, HT waitlist mortality remains high. For highly selected patients with HCM, a left ventricular assist device is a viable option.

Long-term post-transplantation outcomes in patients with hypertrophic cardiomyopathy: Single-center 35-year experience.

BACKGROUND: Heart transplantation (HT) is the only option for most patients with end-stage heart failure and hypertrophic cardiomyopathy (HCM) who fail medical therapy. Data on the long-term outcomes post-transplant in HCM individuals remain scarce. METHODS: We analyzed data of 319 adult patients who underwent HT between 1984 and 2019. Patients were followed for cardiac allograft rejection, cardiac allograft vasculopathy (CAV), death, or re-transplantation. RESULTS: Outcomes of 24 patients with HCM, 160 with ischemic, and 135 with dilated cardiomyopathy were compared. During a mean follow-up of 11.6 ± 7.2 (max 27.8), 16.7 ± 8.2 (max 32.7), and 16.1 ± 9.7 (max 34.6) years after HT in hypertrophic, ischemic, and dilated cardiomyopathy groups, respectively: 10-year survival rate was 67%, 62%, 69%, respectively (p = .04). Post-transplantation, HCM individuals more often than the other two studied groups required prolonged inotropic support (37%, 12%, 17%, respectively, p = .02), temporary mechanical circulatory support (45%, 13%, 14%, respectively, p < .01), and renal replacement therapy immediately post-HT (55%, 19%, 24%, respectively, p < .01). No significant inter-group differences were noted in the 10-year freedom from acute allograft rejection (38%, 46%, 43%, respectively, p = .38) or 10-year freedom from CAV (88%, 78%, 81%, respectively, p = .57). CONCLUSIONS: The long-term post-transplant prognosis of adult patients with hypertrophic cardiomyopathy is favorable despite more challenging immediate post-HT course.

Hypertrophic Cardiomyopathy 2020.

PURPOSE OF REVIEW: To briefly review the pathophysiology and natural history of hypertrophic cardiomyopathy (HCM) and to describe the diagnosis, assessment, and contemporary management strategies. RECENT FINDINGS: HCM-related mortality remains low; however, symptoms due in large part to LVOT obstruction remain a clinical dilemma. Several medical therapies have been shown to reduce symptoms and improve functional capacity, including several recent phase 2 clinical trials involving the novel myosin modulator mavacamten. In patients with refractory symptoms, septal reduction therapy or advanced therapies remain viable options in many cases. HCM is a complex and heterogeneous disease with diverse presentations and variable anatomy and clinical outcomes. The majority of patients will remain asymptomatic or with minimal symptoms and long-term survival remains high. For symptomatic patients, a variety of medical therapies, along with septal reduction therapies, have been shown to reduce symptoms and improve functional capacity.

Cannula Tip With Integrated Volume Sensor for Rotary Blood Pump Control: Early-Stage Development.

The lack of direct measurement of left ventricular unloading is a significant impediment to the development of an automatic speed control system for continuous-flow left ventricular assist devices (cf-LVADs). We have developed an inlet cannula tip for cf-LVADs with integrated electrodes for volume sensing based on conductance. Four platinum-iridium ring electrodes were installed into grooves on a cannula body constructed from polyetheretherketone (PEEK). A sinusoidal current excitation waveform (250 µA pk-pk, 50 kHz) was applied across one pair of electrodes, and the conductance-dependent voltage was sensed across the second pair of electrodes. The conductance catheter was tested in an acute ovine model (n = 3) in conjunction with the HeartMate II rotary blood pump to provide circulatory support and unload the ventricle. Echocardiography was used to measure ventricular size during pump support for verification for the conductance measurements. The conductance measurements correlated linearly with the echocardiography dimension measurements more than the full range of pump support from minimum support to suction. This cannula tip will enable the development of automatic control systems to optimize pump support based on a real-time measurement of ventricular size.

Initial experience with CentriMag extracorporal membrane oxygenation for support of critically ill patients with refractory cardiogenic shock.

BACKGROUND: Cardiogenic shock refractory to conventional therapy has very high mortality and limited support options. New technology with peripherally inserted CentriMag (Levitronix LLC, Waltham, MA) extracorporal membrane oxygenation (ECMO) may have the potential to significantly improve survival in these critically ill patients. Outcomes of the first 10 patients to receive this device at our institutions are presented. METHODS: Patients were identified by their primary physicians and evaluated by our Mechanical Circulatory Support Team. CentriMag ECMO was initiated at the bedside using sterile percutaneous cannulation of femoral vessels. Patients were admitted to the Heart and Vascular Intensive Care Unit, with care managed by regular nursing staff with special training. RESULTS: The patients (5 men, 5 women) were a mean age of 45 +/- 18 years, had a mean left ventricular ejection fraction of 30%, and a mean lactate level of 9 mmol/liter. All patients met criteria for shock refractory to medical therapy, but the etiology varied. Average duration of ECMO support was 5.8 +/- 4 days. Survival was 60%. There were no major complications directly related to the device and no equipment malfunctions. CONCLUSIONS: The peripherally inserted CentriMag ECMO was easy to insert, functioned without mechanical error, and significantly reduced expected mortality in critically ill patients. Further research will be necessary to develop standardized algorithms and gain more experience, but this new technology has promising potential.

Therapeutic implications of implantable device-based monitoring of patients with heart failure.

Heart failure is one of the most common medical problems faced by patients and clinicians. It has the potential for high morbidity and mortality, and its overall financial cost to society is enormous. Management of heart failure is often difficult and time consuming, and is sometimes frustrating. The usual signs and symptoms of heart failure may not be obvious early in an exacerbation, which has prompted the development of other methods to identify early and subtle clinical changes to initiate early intervention. Current implantable devices, such as defibrillators and pacemakers, can monitor changes in heart rate and heart rate variability, patient activity, arrhythmia frequency, and thoracic impedance, all of which may be markers of clinical decline. Newer implantable devices can also measure right ventricular pressures, oxygen saturation, and pulmonary artery pressures. Many of these technologies have been shown to be feasible and potentially helpful, but outcomes data showing reductions in morbidity and mortality are currently limited. Importantly, none of these newer technologies should be used in isolation; all must be used in combination with clinical findings to provide effective disease management.

Cardiac failure: mechanical support strategies.

OBJECTIVE: Mechanical support of the circulation is necessary when heart failure becomes refractory to medical support and is typically applied when organ dysfunction occurs as a result of hypoperfusion. However, in timing the intervention, it is important to apply mechanical support before multiple organ failure occurs. The objective of this work is to review the current strategies for mechanical circulatory support in patients with refractory cardiac failure. DESIGN: A review of the use of mechanical circulatory support is presented for patients with refractory cardiac failure. PATIENTS: Data are taken from human studies that were selected to best exemplify the results that may be obtained from various forms of mechanical circulatory support. INTERVENTIONS: Commonly applied forms of mechanical support include mechanical ventilatory support, intraaortic balloon counterpulsation, and hemodialysis or ultrafiltration. If these measures fail, mechanical support of the circulation with ventricular assist devices is possible in specialized centers with expertise in the implantation and management of these devices. The decision to pursue mechanical circulatory support in the critically ill patient is based on the cause of acute decompensation, the potential reversibility of the condition, and the possibility for other treatments to improve the underlying condition or, in highly selected cases, heart transplantation. Newer forms of ventricular assistance that require less surgery are becoming available and may allow use in a broader range of critically ill patients. MAIN RESULTS: There is a range of means to mechanically support the circulation in patients with advanced heart failure. CONCLUSIONS: A variety of means to support the circulation have found application in the treatment of patients with refractory heart failure. More work is required to best identify populations who will benefit from the therapy and to refine the therapy to reduce associated risks.

A prospective study of continuous intravenous milrinone therapy for status IB patients awaiting heart transplant at home.

BACKGROUND: We performed a prospective study to determine the feasibility and safety of continuous intravenous milrinone therapy administered at home in patients listed as Status IB for heart transplant. METHODS: Patients who were Status IB could participate if they met specific criteria including an optimal dose of milrinone < or =0.5 microg/kg/min, presence of an implantable cardioverter-defibrillator (ICD), and no other serious comorbidity. The primary end-point of the study was survival to transplant. Hospitalizations, quality of life and cost comparisons were assessed. RESULTS: From May 1999 through October 2002, a total of 60 patients (51 men, 9 women), aged 55.5 +/- 8.4 years, entered the study. Before milrinone therapy, cardiac index was 1.98 +/- 0.66 liters/min/m2 and peak oxygen consumption was 11.4 +/- 2.6 ml/kg/min. Mean time in the study was 160.1 +/- 151.8 days. Fifty-three patients (88.3%) underwent heart transplant. There were only 2 deaths during the study. There were 89 hospital admissions in 46 patients over the 43-month follow-up period; 58 of these admissions were for heart failure. There were 6 episodes of ICD firing for ventricular tachycardia. Quality-of-life measures in a sub-group of patients significantly improved 1 month after discharge. Substantial estimated cost savings occurred. CONCLUSIONS: Continuous intravenous milrinone therapy can be safely administered at home in selected patients with advanced heart failure who are listed for transplant. This strategy may be an acceptable alternative to prolonged hospitalization for patients dependent on continuous inotropic support. Re-hospitalization is to be expected. An implantable cardioverter-defibrillator should be present due to the incidence of ventricular tachycardia.

Hypertrophic cardiomyopathy. Pathophysiology, diagnosis, and treatment.

Hypertrophic cardiomyopathy is one of the most common inherited cardiovascular diseases and is characterized by a heterogeneous appearance and natural history. Although previously thought to be a disease of the young, HCM is frequently diagnosed in patients over age 50. A careful history and physical examination and readily available non-invasive testing will diagnose most cases, but genetic testing can identify those not expressing the typical phenotype. Treatment of symptomatic patients is targeted toward improving LV diastolic function; for patients with the obstructive form HCM, treatment involves relieving outflow tract obstruction. Identification of those at risk for sudden death may require consideration of prophylactic defibrillator placement.